﻿PT	AU	BA	BE	GP	AF	BF	CA	TI	SO	SE	BS	LA	DT	CT	CY	CL	SP	HO	DE	ID	AB	C1	C3	RP	EM	RI	OI	FU	FX	CR	NR	TC	Z9	U1	U2	PU	PI	PA	SN	EI	BN	J9	JI	PD	PY	VL	IS	PN	SU	SI	MA	BP	EP	AR	DI	D2	EA	PG	WC	WE	SC	GA	UT	PM	OA	HC	HP	DA
J	Yang, M; Liu, JW; Shao, JH; Qin, YW; Ji, QS; Zhang, XL; Du, J				Yang, Min; Liu, Jingwei; Shao, Jianghua; Qin, Yanwen; Ji, Qunsheng; Zhang, Xiaolin; Du, Jie			Cathepsin S-mediated autophagic flux in tumor-associated macrophages accelerate tumor development by promoting M2 polarization	MOLECULAR CANCER			English	Article						Tumor-associated macrophages; Tumor microenvironment; Cathepsin; Autophagy	BREAST-CANCER; ENDOPLASMIC-RETICULUM; CYSTEINE CATHEPSINS; DENDRITIC CELLS; GROWTH; METASTASIS; EXPRESSION; CARCINOMA; INVASION; STRESS	Background: Tumor-associated macrophages (TAMs) are the major component of tumor-infiltrating leukocytes. TAMs are heterogeneous, with distinct phenotypes influenced by the microenvironment surrounding tumor tissues, but relatively little is known about the key molecular in these cells that contribute to malignant phenotypes. Autophagic activity is a critical factor in tumor development that contributes to enhancing cellular fitness and survival in the hostile tumor microenvironment. However, the molecular basis and relations between autophagy and TAMs polarization remain unclear. Methods: Cathepsin S (Cat S) expression was analyzed in human colon carcinoma and normal colon tissues. In vivo effects were evaluated using PancO2 subcutaneous tumor model and SL4 hepatic metastasis model. Immunofluorescence staining, flow cytometry and real-time PCR were done to examine TAMs polarization. Western blotting assay, transmission electron microscopy, mCherry-GFP-LC3 transfection and DQ-BSA degradation assays were carried out to determine its role in regulating autophagy. Results: In the present study, we showed that the enhanced expression of Cat S correlated with the severity of histologic grade as well as clinical stage, metastasis, and recurrence, which are known indicators of a relatively poor prognosis of human colon carcinoma. Cat S knockout led to decreased tumor growth and metastasis. Moreover, Cat S knockout inhibited M2 macrophage polarization during tumor development. We further demonstrated that Cat S was required for not only autophagic flux but also the fusion processes of autophagosomes and lysosomes in TAMs. Importantly, we found that Cat S contributed to tumor development by regulating the M2 phenotype of TAMs through the activation of autophagy. Conclusions: These results indicated that Cat S-mediated autophagic flux is an important mechanism for inducing M2-type polarization of TAMs, which leads to tumor development. These data provide strong evidence for a tumor-promoting role of autophagy in TAMs and suggest Cat S could be a potential target for cancer therapy.	[Yang, Min; Liu, Jingwei; Qin, Yanwen; Du, Jie] Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China; [Yang, Min; Liu, Jingwei; Qin, Yanwen; Du, Jie] Capital Med Univ, Minist Educ, Beijing Inst Heart Lung & Blood Vessel Dis, Key Lab Remodeling Related Cardiovasc Dis, Beijing 100029, Peoples R China; [Shao, Jianghua] Nanchang Univ, Affiliated Hosp 2, Nanchang 330006, Jiangxi, Peoples R China; [Ji, Qunsheng; Zhang, Xiaolin] AstraZeneca, Innovat Ctr China, Shanghai 201203, Peoples R China		Du, J (corresponding author), Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China.	jdu@bcm.edu	Qin, Yanwen/AAM-6961-2020	Qin, Yanwen/0000-0002-5185-9726	Chinese Ministry of Science and TechnologyMinistry of Science and Technology, China [2009CB522205]; Chinese High Technology Research and Development ProgramNational High Technology Research and Development Program of China [2012AA02A201]; National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81170120]; Beijing Nova ProgramBeijing Municipal Science & Technology Commission [Z121107002512041]	This study was supported by grants from Chinese Ministry of Science and Technology (2009CB522205), Chinese High Technology Research and Development Program (2012AA02A201), National Science Foundation of China (81170120) and Beijing Nova Program (Z121107002512041).	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Cancer	MAR 2	2014	13								43	10.1186/1476-4598-13-43			15	Biochemistry & Molecular Biology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Oncology	AF2JL	WOS:000334538300001	24580730	Green Published, gold			2022-04-25	
J	Rosenfeldt, MT; Ryan, KM				Rosenfeldt, Mathias T.; Ryan, Kevin M.			The role of autophagy in tumour development and cancer therapy	EXPERT REVIEWS IN MOLECULAR MEDICINE			English	Review							PROGRAMMED CELL-DEATH; BCL-X-L; REGULATES AUTOPHAGY; BECLIN 1; COLON-CANCER; PHOSPHATIDYLINOSITOL 3-KINASE; MICROSATELLITE INSTABILITY; EMBRYONIC-DEVELOPMENT; CONJUGATION SYSTEMS; INTERACTING PROTEIN	Autophagy is a catabolic membrane-trafficking process that leads to sequestration and degradation of intracellular material within lysosomes. It is executed at basal levels in every cell and promotes cellular homeostasis by regulating organelle and protein turnover. In response to various forms of cellular stress, however, the levels and cargoes of autophagy can be modulated. In nutrient-deprived states, for example, autophagy can be activated to degrade cargoes for cell-autonomous energy production to promote cell survival. In other contexts, in contrast, autophagy has been shown to contribute to cell death. Given these dual effects in regulating cell viability, it is no surprise that autophagy has implications in both the genesis and treatment of malignant disease. In this review, we provide a comprehensive appraisal of the way in which oncogenes and tumour suppressor genes regulate autophagy. In addition, we address the current evidence from human cancer and animal models that has aided our understanding of the role of autophagy in tumour progression. Finally, the potential for targeting autophagy therapeutically is discussed in light of the functions of autophagy at different stages of tumour progression and in normal tissues.	[Rosenfeldt, Mathias T.; Ryan, Kevin M.] Beatson Inst Canc Res, Tumour Cell Death Lab, Glasgow G61 1BD, Lanark, Scotland		Ryan, KM (corresponding author), Beatson Inst Canc Res, Tumour Cell Death Lab, Garscube Estate,Switchback Rd, Glasgow G61 1BD, Lanark, Scotland.	k.ryan@beatson.gla.ac.uk	Rosenfeldt, Mathias/ABE-4736-2022	Rosenfeldt, Mathias/0000-0001-7650-8458; Ryan, Kevin M./0000-0002-1059-9681	Cancer Research UKCancer Research UK; Association for International Cancer Research	We are grateful to members of the Tumour Cell Death Laboratory for critical reading of the manuscript. We also thank the peer reviewers of our article, whose insightful comments improved the clarity and comprehensive nature of this review. Work in the Tumour Cell Death Laboratory is supported by Cancer Research UK and the Association for International Cancer Research.	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Mol. Med.	DEC 2	2009	11								e36	10.1017/S1462399409001306			20	Biochemistry & Molecular Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Research & Experimental Medicine	577UV	WOS:000276250400001	19951459	Green Published, hybrid			2022-04-25	
J	Mukhopadhyay, S; Sinha, N; Das, DN; Panda, PK; Naik, PP; Bhutia, SK				Mukhopadhyay, Subhadip; Sinha, Niharika; Das, Durgesh Nandini; Panda, Prashanta Kumar; Naik, Prajna Paramita; Bhutia, Sujit Kumar			Clinical relevance of autophagic therapy in cancer: Investigating the current trends, challenges, and future prospects	CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES			English	Review						Autophagy; apoptosis; cancer patients; drugs; therapy; oncophagy; clinical trials; translational medicine	RENAL-CELL-CARCINOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ENDOPLASMIC-RETICULUM STRESS; DUAL PI3K/MTOR INHIBITOR; MEDULLARY-THYROID CANCER; VIVO ANTITUMOR-ACTIVITY; HUMAN OVARIAN-CANCER; BREAST-TUMOR CELLS; COLON-CANCER; LUNG-CANCER	Oncophagy (cancer-related autophagy) has a complex dual character at different stages of tumor progression. It remains an important clinical problem to unravel the reasons that propel the shift in the role of oncophagy from tumor inhibition to a protective mechanism that shields full-blown malignancy. Most treatment strategies emphasize curbing protective oncophagy while triggering the oncophagy that is lethal to tumor cells. In this review, we focus on the trends in current therapeutics as well as various challenges in clinical trials to address the oncophagic dilemma and evaluate the potential of these developing therapies. A detailed analysis of the clinical and pre-clinical scenario of the anticancer medicines highlights the various inducers and inhibitors of autophagy. The ways in which tumor stage, the microenvironment and combination drug treatment continue to play an important tactical role are discussed. Moreover, autophagy targets also play a crucial role in developing the best possible solution to this oncophagy paradox. In this review, we provide a comprehensive update on the current clinical impact of autophagy-based cancer therapeutic drugs and try to lessen the gap between translational medicine and clinical science.	[Mukhopadhyay, Subhadip; Sinha, Niharika; Das, Durgesh Nandini; Panda, Prashanta Kumar; Naik, Prajna Paramita; Bhutia, Sujit Kumar] Natl Inst Technol Rourkela, Dept Life Sci, Rourkela 769008, Odisha, India		Bhutia, SK (corresponding author), Natl Inst Technol Rourkela, Dept Life Sci, Rourkela 769008, Odisha, India.	sbhutia@nitrkl.ac.in	Sinha, Niharika/AFF-4328-2022; Naik, Prajna Paramita/AAV-8237-2020; MUKHOPADHYAY, SUBHADIP/AAM-2459-2020	Sinha, Niharika/0000-0002-5466-4895; Naik, Prajna Paramita/0000-0002-6086-3022; 	Department of Biotechnology [BT/PR1/5090/GBD/27/309/2011]; Science and Engineering Research Board (SERB), the Department of Science and Technology [SR/SO/BB-0101/2012]; Council of Scientific and Industrial Research (CSIR) Human Resource Development Group, Government of India [37(1608)/13/EMR-II]	Research support was partly provided by the Rapid Grant for Young Investigators (RGYI) Award [Grant Number: BT/PR1/5090/GBD/27/309/2011], the Department of Biotechnology [Grant Number: BT/PR7791/BRB/10/1187/2013]; the Science and Engineering Research Board (SERB), the Department of Science and Technology [Grant Number: SR/SO/BB-0101/2012]; the Council of Scientific and Industrial Research (CSIR) [Grant Number: 37(1608)/13/EMR-II] Human Resource Development Group, Government of India. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. We apologize to researchers whose studies on autophagy we were unable to cite due to the length of this review.	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Rev. Clin. Lab. Sci.	AUG	2016	53	4					228	252		10.3109/10408363.2015.1135103			25	Medical Laboratory Technology	Science Citation Index Expanded (SCI-EXPANDED)	Medical Laboratory Technology	DN4IP	WOS:000377029000002	26743568	Green Submitted			2022-04-25	
J	Song, HT; Qin, Y; Yao, GD; Tian, ZN; Fu, SB; Geng, JS				Song, Hong-tao; Qin, Yu; Yao, Guo-dong; Tian, Zhen-nan; Fu, Song-bin; Geng, Jing-shu			Astrocyte Elevated Gene-1 Mediates Glycolysis and Tumorigenesis in Colorectal Carcinoma Cells via AMPK Signaling	MEDIATORS OF INFLAMMATION			English	Article							CANCER; AEG-1; PROGRESSION; AUTOPHAGY; INHIBITION; PATHOGENESIS; METASTASIS; EXPRESSION; SURVIVAL; THERAPY	To investigate the role of AEG-1 in glycolysis and tumorigenesis, we construct myc-AEG-1 expression vector and demonstrate a novel mechanism that AEG-1 may increase the activity of AMPK by Thr172 phosphorylation. The higher expression levels of AEG-1 in colorectal carcinoma cells were found but showed significant difference in different cell lines. To study the role of AEG-1 in colorectal cells, myc-AEG-1 vector was constructed and transfected into NCM460 colonic epithelial cells. We observed consistent increasing of glucose consumption and lactate production, typical features of anaerobic glycolysis, suggesting that AEG-1 may promote anaerobic glycolysis. Moreover, we noted that AMPK phosphorylation at Thr172 as well as pPFK2 (Ser466) was increased in NCM460 cells overexpressing AEG-1. Compound C may block AMPK and PFK2 phosphorylation in both control and AEG1-overexpressed cells and decrease the glucose consumption and lactate production. The present findings indicated that reduced AEG-1 protein levels by RNAi may decrease the glucose consumption and lactate production in HCT116 colorectal carcinoma cells. The present identified AEG-1/AMPK/PFK2 glycolysis cascade may be essential to cell proliferation and tumor growth. The present results may provide us with a mechanistic insight into novel targets controlled by AEG-1, and the components in the AEG1/AMPK/PFK2 glycolysis process may be targeted for the clinical treatment of cancer.	[Song, Hong-tao; Qin, Yu; Yao, Guo-dong; Tian, Zhen-nan; Geng, Jing-shu] Harbin Med Univ, Affiliated Tumor Hosp, Dept Pathol, Harbin 150040, Peoples R China; [Fu, Song-bin; Geng, Jing-shu] Harbin Med Univ, Dept Med Genet, Harbin 150086, Peoples R China		Geng, JS (corresponding author), Harbin Med Univ, Affiliated Tumor Hosp, Dept Pathol, Harbin 150040, Peoples R China.	jingshu0128@163.com			Wu Lien-Teh Science Foundation for Youths of Harbin Medical University [WLD-QN1117]; Foundation of Heilongjiang Educational Committee [12511175]; Foundation of Heilongjiang Provincial Department of Public Health [2011-146]; Scientific Research Staring Foundation; Affiliated Tumor Hospital of Harbin Medical University [JJ 2010-13]	This research was also supported by the Wu Lien-Teh Science Foundation for Youths of Harbin Medical University (Grant no. WLD-QN1117), the Foundation of Heilongjiang Educational Committee (Grant no. 12511175), the Foundation of Heilongjiang Provincial Department of Public Health (Grant no. 2011-146), and the Scientific Research Staring Foundation, the Affiliated Tumor Hospital of Harbin Medical University (Grant no. JJ 2010-13).	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Inflamm.		2014	2014								287381	10.1155/2014/287381			9	Cell Biology; Immunology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Immunology	AG0WP	WOS:000335136700001	24829520	Green Published, gold, Green Submitted			2022-04-25	
J	Tesarova, P; Cabinakova, M; Mikulova, V; Zima, T; Kalousova, M				Tesarova, P.; Cabinakova, M.; Mikulova, V.; Zima, T.; Kalousova, M.			RAGE and its ligands in cancer - culprits, biomarkers, or therapeutic targets?	NEOPLASMA			English	Review						RAGE; cancer; HMGB1; S100 proteins	GLYCATION END-PRODUCTS; ALTERNATIVELY SPLICED RAGEV1; SOLUBLE FORM SRAGE; ENDPRODUCTS RAGE; MELANOMA GROWTH; RECEPTOR; EXPRESSION; RISK; POLYMORPHISM; AGES	Receptor for advanced glycation end products (RAGE) plays a central role in the regulation of tissue homeostasis, regeneration and resolution of inflammation, but under pathological conditions RAGE-mediated pathways may induce diminished apoptosis, but enhanced autophagy and cell necrosis. These mechanisms may contribute to malignant transformation, cancer progression and metastases. Soluble RAGE may bind natural RAGE ligands and counteract some of the RAGE-mediated effects. Activation of RAGE was demonstrated in different types of cancer (including colon, pancreatic and breast cancer). Expression of RAGE and serum levels of soluble RAGE may serve as cancer biomarkers and strategies aimed at interfering with RAGE signaling might be promising anticancer drugs.	[Tesarova, P.; Cabinakova, M.] Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic; [Tesarova, P.; Cabinakova, M.; Mikulova, V.; Zima, T.; Kalousova, M.] Gen Univ Hosp, Prague, Czech Republic; [Mikulova, V.; Zima, T.; Kalousova, M.] Charles Univ Prague, Inst Med Biochem & Lab Diagnost, Fac Med 1, Prague, Czech Republic		Tesarova, P (corresponding author), Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic.	tesarova.petra@seznam.cz	cabinakova, Michaela/C-1083-2017; Tesarová, P/AAC-3053-2019; Tesarova, Petra/A-8718-2017; Zima, Tomas/F-6760-2017; Kalousova, Marta/D-1530-2017	cabinakova, Michaela/0000-0003-2766-2090; Tesarova, Petra/0000-0003-3607-3474; Zima, Tomas/0000-0001-8518-6972; Kalousova, Marta/0000-0001-5928-3074; Mikulova, Veronika/0000-0002-9962-5312	 [MH CZ - RVO VFN 64641 VFN 64164];  [PRVOUK - P25/LF1/2]	Studies of the authors on RAGE were supported by research projects MH CZ - RVO VFN 64641 VFN 64164 and PRVOUK - P25/LF1/2.	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J	Pigna, E; Berardi, E; Aulino, P; Rizzuto, E; Zampieri, S; Carraro, U; Kern, H; Merigliano, S; Gruppo, M; Mericskay, M; Li, ZL; Rocchi, M; Barone, R; Macaluso, F; Di Felice, V; Adamo, S; Coletti, D; Moresi, V				Pigna, Eva; Berardi, Emanuele; Aulino, Paola; Rizzuto, Emanuele; Zampieri, Sandra; Carraro, Ugo; Kern, Helmut; Merigliano, Stefano; Gruppo, Mario; Mericskay, Mathias; Li, Zhenlin; Rocchi, Marco; Barone, Rosario; Macaluso, Filippo; Di Felice, Valentina; Adamo, Sergio; Coletti, Dario; Moresi, Viviana			Aerobic Exercise and Pharmacological Treatments Counteract Cachexia by Modulating Autophagy in Colon Cancer	SCIENTIFIC REPORTS			English	Article							QUALITY-OF-LIFE; SKELETAL-MUSCLE; PHYSICAL-ACTIVITY; ENVIRONMENTAL ENRICHMENT; MUSCULAR-DYSTROPHY; AMPK; ACTIVATION; DISEASE; HEALTH; PHOSPHORYLATION	Recent studies have correlated physical activity with a better prognosis in cachectic patients, although the underlying mechanisms are not yet understood. In order to identify the pathways involved in the physical activity-mediated rescue of skeletal muscle mass and function, we investigated the effects of voluntary exercise on cachexia in colon carcinoma (C26)-bearing mice. Voluntary exercise prevented loss of muscle mass and function, ultimately increasing survival of C26-bearing mice. We found that the autophagic flux is overloaded in skeletal muscle of both colon carcinoma murine models and patients, but not in running C26-bearing mice, thus suggesting that exercise may release the autophagic flux and ultimately rescue muscle homeostasis. Treatment of C26-bearing mice with either AICAR or rapamycin, two drugs that trigger the autophagic flux, also rescued muscle mass and prevented atrogene induction. Similar effects were reproduced on myotubes in vitro, which displayed atrophy following exposure to C26-conditioned medium, a phenomenon that was rescued by AICAR or rapamycin treatment and relies on autophagosome-lysosome fusion (inhibited by chloroquine). Since AICAR, rapamycin and exercise equally affect the autophagic system and counteract cachexia, we believe autophagy-triggering drugs may be exploited to treat cachexia in conditions in which exercise cannot be prescribed.	[Pigna, Eva; Berardi, Emanuele; Aulino, Paola; Adamo, Sergio; Coletti, Dario; Moresi, Viviana] Univ Roma La Sapienza, Interuniv Inst Myol, DAHFMO Unit Histol & Med Embryol, Rome, Italy; [Berardi, Emanuele] Katholieke Univ Leuven, Res Grp Exercise Physiol, Dept Kinesiol, Leuven, Belgium; [Rizzuto, Emanuele] Univ Roma La Sapienza, Dept Mech & Aerosp Engn, Rome, Italy; [Zampieri, Sandra] Univ Padua, Dept Biomed Sci, I-35100 Padua, Italy; [Zampieri, Sandra; Kern, Helmut] Wilhelminenspital Wien, Dept Phys Med & Rehabil, Ludwig Boltzmann Inst Elect Stimulat & Phys Rehab, Vienna, Austria; [Carraro, Ugo] IRCCS Fdn Osped San Camillo, Venice, Italy; [Merigliano, Stefano; Gruppo, Mario] Univ Padua, Dept Surg & Gastroenterol Sci, I-35100 Padua, Italy; [Mericskay, Mathias; Li, Zhenlin; Coletti, Dario] Univ Paris 06, INSERM, Dept Biol Adaptat & Ageing B2A, CNRS,UMR 8256,ERL,U1164, F-75252 Paris 05, France; [Rocchi, Marco] Carlo Bo Univ Urbino, Unit Biostat, Dept Biomol Sci, Urbino, Italy; [Barone, Rosario; Macaluso, Filippo; Di Felice, Valentina] Univ Palermo, Dept Expt Biomed & Clin Neurosci BioNeC, I-90133 Palermo, Italy		Adamo, S (corresponding author), Univ Roma La Sapienza, Interuniv Inst Myol, DAHFMO Unit Histol & Med Embryol, Rome, Italy.	sergio.adamo@uniroma1.it	Gruppo, Mario/ABD-1695-2020; Gruppo, Mario/G-7282-2014; Rocchi, Marco BL/AAK-5926-2021; barone, rosario/ABA-6758-2021; Merigliano, Stefano/AAY-3023-2021; Barone, Rosario/ABD-8488-2020; Berardi, Emanuele/AAC-9753-2019; zampieri, sandra/AAJ-5400-2021; Adamo, Sergio/E-9058-2012; Di Felice, Valentina/A-4457-2009; Coletti, Dario/U-2219-2018; Di Felice, Valentina/AAG-3740-2021; Rizzuto, Emanuele/K-9437-2016; MERICSKAY, Mathias/M-3477-2018	Gruppo, Mario/0000-0001-5525-5762; Gruppo, Mario/0000-0001-5525-5762; Berardi, Emanuele/0000-0002-0775-9605; zampieri, sandra/0000-0001-6970-0011; Adamo, Sergio/0000-0002-1409-0452; Di Felice, Valentina/0000-0002-4132-1260; Di Felice, Valentina/0000-0002-4132-1260; Moresi, viviana/0000-0003-1912-0339; Coletti, Dario/0000-0001-7373-1953; Rizzuto, Emanuele/0000-0003-2314-6128; Rocchi, marco/0000-0002-0056-5795; barone, rosario/0000-0002-8240-1240; Kern, Helmut/0000-0001-9661-8814; Carraro, Ugo/0000-0002-0924-4998; MERICSKAY, Mathias/0000-0002-6779-092X; LI, Zhenlin/0000-0002-3706-4505	ANRFrench National Research Agency (ANR) [13-BSV1-0005]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [5R01CA180057-02]; AFMAssociation Francaise contre les Myopathies [2012-0773]; UPMC Emergence; IBPS; PRINMinistry of Education, Universities and Research (MIUR)Research Projects of National Relevance (PRIN) [2012N8YJC3, 2009WBFZYM 001]; European Regional Development Fund-Cross Border Cooperation Programme SLOVAKIA-AUSTRIA (Interreg-Iva) project "Mobilitat im Alter" MOBIL [00033]; Austrian Federal Ministry of Science and Research; Ludwig Boltzmann Society (Vienna); NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA180057] Funding Source: NIH RePORTER	D. Coletti is supported by ANR (# 13-BSV1-0005), NIH (# 5R01CA180057-02), AFM (# 2012-0773), UPMC Emergence 2011 and IBPS 2015. Z. Li is supported by ANR and AFM. We also acknowledge PRIN 2009 (Project 2009WBFZYM 001) and PRIN 2011 Project # 2012N8YJC3) grants to S. Adamo. S. Zampieri, U. Carraro and H. Kern are supported by the European Regional Development Fund-Cross Border Cooperation Programme SLOVAKIA-AUSTRIA (Interreg-Iva) project "Mobilitat im Alter" MOBIL N_00033; Austrian Federal Ministry of Science and Research; Ludwig Boltzmann Society (Vienna). The authors are indebted to Carla Ramina for her precious technical assistance. They gratefully thank Richard Lowry, Ph.D., Professor Emeritus of Psychology at the Vassar College, for his web-based, user-friendly tool for performing statistical computation, VassarStats, which they used for the statistical analysis, and Daniela Annibali for her critical comments.	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J	Sui, X; Chen, R; Wang, Z; Huang, Z; Kong, N; Zhang, M; Han, W; Lou, F; Yang, J; Zhang, Q; Wang, X; He, C; Pan, H				Sui, X.; Chen, R.; Wang, Z.; Huang, Z.; Kong, N.; Zhang, M.; Han, W.; Lou, F.; Yang, J.; Zhang, Q.; Wang, X.; He, C.; Pan, H.			Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment	CELL DEATH & DISEASE			English	Review						autophagy; chemotherapy resistance; cancer; therapy	ACTIVATED PROTEIN-KINASE; CELL-DEATH; INDUCED APOPTOSIS; HEPATOCELLULAR-CARCINOMA; COLON-CANCER; ER STRESS; INHIBITOR NVP-BEZ235; DRUG-RESISTANCE; 3-KINASE/MAMMALIAN TARGET; OVERCOMES RESISTANCE	Induction of cell death and inhibition of cell survival are the main principles of cancer therapy. Resistance to chemotherapeutic agents is a major problem in oncology, which limits the effectiveness of anticancer drugs. A variety of factors contribute to drug resistance, including host factors, specific genetic or epigenetic alterations in the cancer cells and so on. Although various mechanisms by which cancer cells become resistant to anticancer drugs in the microenvironment have been well elucidated, how to circumvent this resistance to improve anticancer efficacy remains to be defined. Autophagy, an important homeostatic cellular recycling mechanism, is now emerging as a crucial player in response to metabolic and therapeutic stresses, which attempts to maintain/restore metabolic homeostasis through the catabolic lysis of excessive or unnecessary proteins and injured or aged organelles. Recently, several studies have shown that autophagy constitutes a potential target for cancer therapy and the induction of autophagy in response to therapeutics can be viewed as having a prodeath or a prosurvival role, which contributes to the anticancer efficacy of these drugs as well as drug resistance. Thus, understanding the novel function of autophagy may allow us to develop a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes in the treatment of cancer patients.	[Sui, X.; Wang, Z.; Kong, N.; Han, W.; Lou, F.; Yang, J.; Wang, X.; Pan, H.] Zhejiang Univ, Dept Med Oncol, Sir Run Run Shaw Hosp, Hangzhou 310016, Zhejiang, Peoples R China; [Chen, R.; Huang, Z.; Zhang, M.; He, C.] Zhejiang Univ, Dept Colorectal Surg, Sir Run Run Shaw Hosp, Hangzhou 310016, Zhejiang, Peoples R China; [Zhang, Q.] Zhejiang Prov Peoples Hosp, Dept Gastrointestinal Surg, Hangzhou, Zhejiang, Peoples R China; [Wang, X.; He, C.; Pan, H.] Biomed Res Ctr, Hangzhou, Zhejiang, Peoples R China; [Wang, X.; He, C.; Pan, H.] Key Lab Biotherapy Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China		Wang, X (corresponding author), Zhejiang Univ, Dept Med Oncol, Sir Run Run Shaw Hosp, Hangzhou 310016, Zhejiang, Peoples R China.	wangxzju@163.com; drhechao@yahoo.com.cn; drpanhm@aliyun.com		Wang, Xian/0000-0003-0041-7589	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81301891, 81272593, 81071651, 81071963]; Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [LQ13H160008]	This study is supported by grants from the National Natural Science Foundation of China (grants 81301891, 81272593, 81071651 and 81071963) and the Zhejiang Provincial Natural Science Foundation of China (grant LQ13H160008).	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Zhao MY, 2011, BMB REP, V44, P601, DOI 10.5483/BMBRep.2011.44.9.601; Zhao S, 2012, INT J MOL MED, V30, P939, DOI 10.3892/ijmm.2012.1066; Zhao Y, 2012, MAR DRUGS, V10, P1345, DOI 10.3390/md10061345; Zou ZZ, 2012, AUTOPHAGY, V8, P1798, DOI 10.4161/auto.22110; Zou ZY, 2012, J BIOL CHEM, V287, P4148, DOI 10.1074/jbc.M111.307405	121	773	796	14	167	SPRINGERNATURE	LONDON	CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND	2041-4889			CELL DEATH DIS	Cell Death Dis.	OCT	2013	4								e838	10.1038/cddis.2013.350			12	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	251XK	WOS:000326967100024	24113172	gold, Green Published	Y	N	2022-04-25	
J	Jiang, LQ; Wang, YJ; Yin, QF; Liu, GX; Liu, HH; Huang, YJ; Li, B				Jiang, Liangqian; Wang, Yujuan; Yin, Qifeng; Liu, Guoxiang; Liu, Huihui; Huang, Yajing; Li, Bing			Phycocyanin: A Potential Drug for Cancer Treatment	JOURNAL OF CANCER			English	Review						Phycocyanin; Apoptosis; Autophagy; Cancer; Cell cycle arrest	NF-KAPPA-B; CYANOBACTERIUM SYNECHOCOCCUS-VULCANUS; SELECTIVE CYCLOOXYGENASE-2 INHIBITOR; SELENIUM-CONTAINING PHYCOCYANIN; PROTEIN C-PHYCOCYANIN; TRANS-RETINOIC ACID; SPIRULINA-PLATENSIS; CRYSTAL-STRUCTURE; IN-VITRO; COLON CARCINOGENESIS	Phycocyanin isolated from marine organisms has the characteristics of high efficiency and low toxicity, and it can be used as a functional food. It has been reported that phycocyanin has anti-oxidative function, anti-inflammatory activity, anti-cancer function, immune enhancement function, liver and kidney protection pharmacological effects. Thus, phycocyanin has an important development and utilization as a potential drug, and phycocyanin has become a new hot spot in the field of drug research. So far, there are more and more studies have shown that phycocyanin has the anti-cancer effect, which can block the proliferation of cancer cells and kill cancer cells. Phycocyanin exerts anti-cancer activity by blocking tumor cell cell cycle, inducing tumor cell apoptosis and autophagy, thereby phycocyanin can serve as a promising anti-cancer agent. This review discusses the therapeutic use of phycocyanin and focuses on the latest advances of phycocyanin as a promising anti-cancer drug.	[Jiang, Liangqian; Wang, Yujuan; Yin, Qifeng; Liu, Guoxiang; Liu, Huihui; Li, Bing] Qingdao Univ, Basic Med Coll, Dept Genet & Cell Biol, 308 Ningxia Rd, Qingdao 266071, Peoples R China; [Huang, Yajing] Qingdao Univ, Basic Med Coll, 308 Ningxia Rd, Qingdao 266071, Peoples R China		Li, B (corresponding author), Qingdao Univ, Basic Med Coll, Dept Genet & Cell Biol, 308 Ningxia Rd, Qingdao 266071, Peoples R China.	jiang8014@163.com; libing_516619@163.com		Li, Bing/0000-0002-5545-9674	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81471546, 81001346, 81273206]	This work was funded by the National Natural Science Foundation of China (81471546, 81001346, 81273206).	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Cancer		2017	8	17					3416	3429		10.7150/jca.21058			14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	FQ6TN	WOS:000418497000005	29151925	Green Published, Green Submitted, gold			2022-04-25	
J	Heller, L; Knorrscheidt, A; Flemming, F; Wiemann, J; Sommerwerk, S; Pavel, IZ; Al-Harrasi, A; Csuk, R				Heller, Lucie; Knorrscheidt, Anja; Flemming, Franziska; Wiemann, Jana; Sommerwerk, Sven; Pavel, Ioana Z.; Al-Harrasi, Ahmed; Csuk, Rene			Synthesis and proapoptotic activity of oleanolic acid derived amides	BIOORGANIC CHEMISTRY			English	Article						Oleanolic acid; Amides; Tumor cells; Cell-cycle arrest; Apoptosis; Autophagy	URSOLIC ACID; MONODANSYLCADAVERINE MDC; MOLECULAR-MECHANISMS; AUTOPHAGIC VACUOLES; COLORECTAL-CANCER; DERIVATIVES; TRITERPENOIDS; OLIVES; CELLS; PERSPECTIVES	Thirty-one different 3-O-acetyl-OA derived amides have been prepared and screened for their cytotoxic activity. In the SRB assays nearly all the carboxamides displayed good cytotoxicity in the low mu M range for several human tumor cell lines. Low EC50 values were obtained especially for the picolinylamides 14-16, for a N-[2-(dimethylamino)-ethyl] derivative 27 and a N-[2-(pyrrolinyl)-ethyl] carboxamide 28. These compounds were submitted to an extensive biological testing and proved compound 15 to act mainly by an arrest of the tumor cells in the S phase of the cell cycle. Cell death occurred by autophagy while compounds 27 and 28 triggered apoptosis. (C) 2016 Elsevier Inc. All rights reserved.	[Heller, Lucie; Knorrscheidt, Anja; Flemming, Franziska; Wiemann, Jana; Sommerwerk, Sven; Csuk, Rene] Martin Luther Univ Halle Wittenberg, Organ Chem, Kurt Mothes Str 2, D-06120 Halle, Saale, Germany; [Pavel, Ioana Z.] Victor Babes Univ Med & Pharm, Dept Pathophysiol, Eftimie Murgu Sq 30004, Timisoara 300173, Romania; [Pavel, Ioana Z.] Victor Babes Univ Med & Pharm, Dept Pharmacognosy, Eftimie Murgu Sq 30004, Timisoara 300173, Romania; [Al-Harrasi, Ahmed] Univ Nizwa, Chair Omans Med Plants & Marine Nat Prod, POB 33, Birkat Al Mauz, Nizwa, Oman		Csuk, R (corresponding author), Martin Luther Univ Halle Wittenberg, Bereich Organ Chem, Kurt Mothes Str 2, D-06120 Halle, Saale, Germany.	rene.csuk@chemie.uni-halle.de	Csuk, René/L-1549-2015	Csuk, René/0000-0001-7911-290X; Wiemann, Jana/0000-0003-2608-0320; Heller, Lucie/0000-0002-6735-7026; Pavel, Ioana Zinuca/0000-0002-2223-5228	WissenschaftsCampus Halle WCH; Oman Research CouncilMinistry of Higher Education, Research & Innovation, OmanThe Research Council Oman [ORG/HSS/14/004]	We like to thank Dr. R. Kluge for measuring the MS spectra and Dr. D. Strohl and his team for the NMR spectra. Thanks are also due to to Mrs. J. Wiese, MSc, for measuring the IR spectra and optical rotations and to Mrs. J. Pech for the micro-analyses. The cell lines were kindly provided by Dr. Th. Muller (Dept. of Haematology/Oncology, Martin-Luther Universitat Halle-Wittenberg). Support by the "WissenschaftsCampus Halle WCH" and the Oman Research Council (ORG/HSS/14/004) is gratefully recognized.	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J	Grimm, WA; Messer, JS; Murphy, SF; Nero, T; Lodolce, JP; Weber, CR; Logsdon, MF; Bartulis, S; Sylvester, BE; Springer, A; Dougherty, U; Niewold, TB; Kupfer, SS; Ellis, N; Huo, DH; Bissonnette, M; Boone, DL				Grimm, Wesley A.; Messer, Jeannette S.; Murphy, Stephen F.; Nero, Thomas; Lodolce, James P.; Weber, Christopher R.; Logsdon, Mark F.; Bartulis, Sarah; Sylvester, Brooke E.; Springer, Amanda; Dougherty, Urszula; Niewold, Timothy B.; Kupfer, Sonia S.; Ellis, Nathan; Huo, Dezheng; Bissonnette, Marc; Boone, David L.			The Thr300Ala variant in ATG16L1 is associated with improved survival in human colorectal cancer and enhanced production of type I interferon	GUT			English	Article							GENOME-WIDE ASSOCIATION; PROSTATE-CANCER; CROHN-DISEASE; AUTOPHAGY; VIRUS; CELLS; SUSCEPTIBILITY; THERAPY; ALPHA; ACTIVATION	Objective ATG16L1 is an autophagy gene known to control host immune responses to viruses and bacteria. Recently, a non-synonymous single-nucleotide polymorphism in ATG16L1 (Thr300Ala), previously identified as a risk factor in Crohn's disease (CD), was associated with more favourable clinical outcomes in thyroid cancer. Mechanisms underlying this observation have not been proposed, nor is it clear whether an association between Thr300Ala and clinical outcomes will be observed in other cancers. We hypothesised that Thr300Ala influences clinical outcome in human colorectal cancer (CRC) and controls innate antiviral pathways in colon cancer cells. Design We genotyped 460 patients with CRC and assessed for an association between ATG16L1 Thr300Ala and overall survival and clinical stage. Human CRC cell lines were targeted by homologous recombination to examine the functional consequence of loss of ATG16L1, or introduction of the Thr300Ala variant. Results We found an association between longer overall survival, reduced metastasis and the ATG16L1 Ala/Ala genotype. Tumour sections from ATG16L1 Ala/Ala patients expressed elevated type I interferons (IFN-I)-inducible, MxA, suggesting that differences in cytokine production may influence disease progression. When introduced into human CRC cells by homologous recombination, the Thr300Ala variant did not affect bulk autophagy, but increased basal production of type I IFN. Introduction of Thr300Ala resulted in increased sensitivity to the dsRNA mimic poly(I:C) through a mitochondrial antiviral signalling (MAVS)-dependent pathway. Conclusions The CD-risk allele, Thr300Ala, in ATG16L1 is associated with improved overall survival in human CRC, generating a rationale to genotype ATG16L1 Thr300Ala in patients with CRC. We found that Thr300A alters production of MAVS-dependent type I IFN in CRC cells, providing a mechanism that may influence clinical outcomes.	[Grimm, Wesley A.; Messer, Jeannette S.; Murphy, Stephen F.; Nero, Thomas; Lodolce, James P.; Logsdon, Mark F.; Bartulis, Sarah; Sylvester, Brooke E.; Springer, Amanda; Dougherty, Urszula; Niewold, Timothy B.; Kupfer, Sonia S.; Ellis, Nathan; Huo, Dezheng; Bissonnette, Marc] Univ Chicago, Dept Med, Chicago, IL 60637 USA; [Weber, Christopher R.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA; [Boone, David L.] Indiana Univ Sch Med, Dept Microbiol, 1234 N Notre Dame Ave, South Bend, IN 46617 USA; [Boone, David L.] Indiana Univ Sch Med, Dept Immunol, 1234 N Notre Dame Ave, South Bend, IN 46617 USA		Boone, DL (corresponding author), Indiana Univ Sch Med, Dept Microbiol, 1234 N Notre Dame Ave, South Bend, IN 46617 USA.; Boone, DL (corresponding author), Indiana Univ Sch Med, Dept Immunol, 1234 N Notre Dame Ave, South Bend, IN 46617 USA.	daboone@iu.edu	Kupfer, Sonia S/ABD-9416-2021; Niewold, Timothy B/D-2669-2018	Weber, Christopher/0000-0002-2117-3184; Messer, Jeannette/0000-0002-5072-3835	Crohn's and Colitis Foundation of America [0-34493-1362]; Broad medical Research Foundation [IBD-0259, F32DK082104];  [AI083375-01];  [DK42086]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA164124, U01CA153060] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01AI083375, T32AI007090] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [F32DK082104, P30DK042086] Funding Source: NIH RePORTER	Grant support: AI083375-01; DK42086; Crohn's and Colitis Foundation of America 0-34493-1362; Broad medical Research Foundation IBD-0259 (to DLB) F32DK082104 (to JSM).	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J	Wang, Z; Zhang, M; Shan, R; Wang, YJ; Chen, J; Huang, J; Sun, LQ; Zhou, WB				Wang, Zhan; Zhang, Min; Shan, Rong; Wang, Yu-Jie; Chen, Juan; Huang, Juan; Sun, Lun-Quan; Zhou, Wei-Bing			MTMR3 is upregulated in patients with breast cancer and regulates proliferation, cell cycle progression and autophagy in breast cancer cells	ONCOLOGY REPORTS			English	Article						breast cancer; myotubularin related protein 3; proliferation; cell cycle; autophagy	EXPRESSION; MIGRATION; ANLN; CDK2; P21	As a member of the myotubularin family, myotubularin related protein 3 (MTMR3) has been demonstrated to participate in tumor development, including oral and colon cancer. However, little is known about its functional roles in breast cancer. In the present study, the expression of MTMR3 in breast cancer was evaluated by immunohistochemical staining of tumor tissues from 172 patients. Online data was then used for survival analysis from the PROGgeneV2 database. In vitro, MTMR3 expression was silenced in MDA-MB-231 cells via lentiviral shRNA transduction. MTT, colony formation and flow cytometry assays were performed in the control and MTMR3-silenced cells to evaluate the cell growth, proliferation and cell cycle phase distribution, respectively. Western blotting was used to evaluate the protein expression levels of autophagy-related markers. The results demonstrated that the expression of MTMR3 in breast cancer tissues was significantly increased compared with adjacent normal tissues. MTMR3 was highly expressed in triple-negative breast cancer and was associated with disease recurrence. MTMR3 knockdown in MDA-MB-231 cells inhibited cell proliferation and induced cell cycle arrest and autophagy. The present results indicated that MTMR3 may have an important role in promoting the progression of breast cancer, and its inhibition may serve as a promising therapeutic target for breast cancer treatment.	[Wang, Zhan; Zhang, Min; Shan, Rong; Wang, Yu-Jie; Zhou, Wei-Bing] Cent South Univ, Xiangya Hosp, Dept Oncol, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China; [Chen, Juan] Cent South Univ, Xiangya Hosp, Dept Pharm, Changsha 410008, Hunan, Peoples R China; [Huang, Juan] Cent South Univ, Xiangya Hosp, Hunan Prov Clin Meditech Res Ctr Breast Canc, Changsha 410008, Hunan, Peoples R China; [Sun, Lun-Quan] Cent South Univ, Xiangya Hosp, Ctr Mol Med, Changsha 410008, Hunan, Peoples R China		Zhou, WB (corresponding author), Cent South Univ, Xiangya Hosp, Dept Oncol, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China.	zhouweibing298@csu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572612, 81372842, 81803640]; Hunan Provincial Natural Science FoundationNatural Science Foundation of Hunan Province [2015JJ2183]; Youth Science Foundation of Xiangya Hospital, Central South University [2017Q02]; Research Innovation Program for Graduate Students of Central South University [2018zzts912]; National Key Clinical Specialist Construction Programs of China [2014kll]	This study was supported by grants from the National Natural Science Foundation of China (grant nos. 81572612, 81372842 and 81803640), the Hunan Provincial Natural Science Foundation (grant no. 2015JJ2183), the Youth Science Foundation of Xiangya Hospital, Central South University (grant no. 2017Q02) and the Research Innovation Program for Graduate Students of Central South University (grant no. 2018zzts912). This study was also supported by the National Key Clinical Specialist Construction Programs of China (grant no. 2014kll).	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Rep.	NOV	2019	42	5					1915	1923		10.3892/or.2019.7292			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	JE9BA	WOS:000490982300026	31485632	Green Published, hybrid			2022-04-25	
J	Zhang, H; Wang, YB; Liu, JY; Kuerban, K; Li, J; Iminjan, M; Ye, L				Zhang, Hui; Wang, Yongbing; Liu, Jiayang; Kuerban, Kudelaidi; Li, Jian; Iminjan, Mubarak; Ye, Li			Traditional Uyghur medicine Quercus infectoria galls water extract triggers apoptosis and autophagic cell death in colorectal cancer cells	BMC COMPLEMENTARY MEDICINE AND THERAPIES			English	Article						Quercuse infectoria galls; Colorectal cancer; Apoptosis; Autophagy; Reactive oxygen species	PATHWAYS; THERAPY	Background The water extract of Quercuse infectoria galls (QIG) is the active ingredient of Uyghur medicine Xipayi Kui Jie'an (KJA) which has promising therapeutic effects on Ulcerative Colitis (UC) as an alternative medicine. Considering the relationship between UC and the development of colorectal cancer (CRC), the present work aims to explore the direct anti-CRC activity of QIG extract. Methods CCK8 assay and flow cytometry were used to detect cytotoxicity and apoptosis. Transmission electron microscopy (TEM), flow cytometry, laser confocal and western blotting were performed to examine autophagy. We also adopted Reactive Oxygen Assay kit, as well as transwell and wound healing tests to study the underlying mechanism of QIG against CRC cells. Results First, we found that QIG extract could suppress the viability of CRC cells and trigger caspases-dependent apoptosis. Subsequently, we proved for the first time that QIG extract also triggered autophagic cell death in CRC cells, which together with apoptosis contributed to the cytotoxic effect on CRC cells. Further investigation revealed that QIG-induced cytotoxicity associated with intracellular ROS accumulation which could suppress the AKT/mTOR signaling pathway, and then induce autophagy and inhibit cell growth. Besides, Erk signaling pathway was also involved in the process of autophagic cell death. Moreover, QIG extract also influenced EMT process and inhibited CRC cell migration. Conclusion Altogether, this study provides a basis for the utilization of QIG as an alternative medicine for CRC prevention and treatment.	[Zhang, Hui; Liu, Jiayang; Kuerban, Kudelaidi; Ye, Li] Fudan Univ, Sch Pharm, Dept Biol Med, Shanghai 201203, Peoples R China; [Zhang, Hui; Liu, Jiayang; Kuerban, Kudelaidi; Ye, Li] Fudan Univ, Sch Pharm, Shanghai Engn Res Ctr Immunotherapeut, Shanghai 201203, Peoples R China; [Wang, Yongbing] Shanghai Univ Med & Hlth Sci, Pudong New Area Peoples Hosp, Shanghai 201200, Peoples R China; [Li, Jian] Fudan Univ, Zhongshan Hosp, Minhang Branch, Endoscopy Ctr, Shanghai 200433, Peoples R China; [Iminjan, Mubarak] Xinjiang Med Univ, Coll Pharm, Dept Pharmaceut & Phys Chem, Xinjiang 830011, Peoples R China		Ye, L (corresponding author), Fudan Univ, Sch Pharm, Dept Biol Med, Shanghai 201203, Peoples R China.; Ye, L (corresponding author), Fudan Univ, Sch Pharm, Shanghai Engn Res Ctr Immunotherapeut, Shanghai 201203, Peoples R China.; Iminjan, M (corresponding author), Xinjiang Med Univ, Coll Pharm, Dept Pharmaceut & Phys Chem, Xinjiang 830011, Peoples R China.	896612093@qq.com; yelil@fudan.edu.cn	kuerban, kudelaidi/AAP-5963-2021	Ye, Li/0000-0001-5303-2549	Scientific and Innovative Action Plan of Shanghai [18431902800, 20S11901600]; Key Discipline Construction Project of Pudong Health Bureau of Shanghai [PWZxk2017-11]; Shanghai Natural Science Foundation ProjectNatural Science Foundation of Shanghai [19ZR1446100]	This work was supported by Scientific and Innovative Action Plan of Shanghai (No. 18431902800 and 20S11901600), the Key Discipline Construction Project of Pudong Health Bureau of Shanghai (No. PWZxk2017-11) and Shanghai Natural Science Foundation Project (No. 19ZR1446100).	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J	Dorr, RT; Samulitis, BK; Wisner, L; Han, HY; Zhao, Y; Beroza, P; Damodaran, K; Igarashi, S; Landowski, TH; Von Hoff, DD				Dorr, Robert T.; Samulitis, Betty K.; Wisner, Lee; Han, Haiyong; Zhao, Yu; Beroza, Paul; Damodaran, Komath; Igarashi, Suzu; Landowski, Terry H.; Von Hoff, Daniel D.			Characterization of a membrane-active anti-tumor agent, UA8967	INVESTIGATIONAL NEW DRUGS			English	Article						DPC4; Membrane integrity; SMAD4; TRAP; UA8967; Autophagy	GROWTH; INHIBITOR; APOPTOSIS; PROTEIN	Deletions or mutations in the tumor suppressor gene DPC4 (deleted in pancreatic carcinoma locus 4) are common in colon and pancreatic cancers. Using the Target-related Affinity Profiling (TRAP) chemical library screening method, a novel agent, UA8967, was selected for further studies because it showed greater potency in DPC4-deleted HCT-116 colon cancer cells. Cytotoxicity studies in six pancreatic cancer cell lines (MiaPaca-2, Panc-1, BxPC3, CF-PAC1, AsPC1, and T3M4), one normal human pancreatic ductal epithelial line (HPDE-6) and the HCT-116 DPC4(+/+) and HCT-116 DPC4(-/-) colon cancer cells showed IC(50)s ranging from 12-61 mu M for exposure times of 72 h. Analysis of schedule dependence showed no advantage for long drug exposure times. There was also no selective inhibition of DNA, RNA or protein synthesis after exposure to UA8967. At 24-48 h, there was an accumulation of cells in G(0)/G(1)-phase and a proportionate reduction in S-phase cells. Within 1-6 h of exposure, cells were found to undergo an autophagic response, followed at 24 h by a low level of caspase-independent apoptosis with some necrosis. Because of the relatively non-specific mechanistic effects of UA8967, plasma membrane viability was evaluated using uptake of trypan blue and SytoxA (R) Green dyes, and leakage of LDH. There was a dose dependent increase in SytoxA (R) Green staining, trypan blue uptake and LDH leakage with increasing concentrations of UA8967, suggesting that UA8967 is affecting the plasma membrane. The DPC4(-/-) cells were more sensitive to UA8967 but not to DMSO, suggesting a drug-specific effect on cell membrane integrity.	[Dorr, Robert T.; Samulitis, Betty K.; Wisner, Lee; Igarashi, Suzu; Landowski, Terry H.] Univ Arizona, Ctr Canc, Tucson, AZ 85724 USA; [Han, Haiyong; Zhao, Yu; Von Hoff, Daniel D.] Translat Genom Res Inst TGEN, Phoenix, AZ 85004 USA; [Beroza, Paul; Damodaran, Komath] Telik Inc, Palo Alto, CA 94304 USA		Dorr, RT (corresponding author), Univ Arizona, Ctr Canc, 1515 N Campbell Ave,Rm 4963C, Tucson, AZ 85724 USA.	bdorr@azcc.arizona.edu			National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01-CA109552]; University of Arizona Cancer Center Support Core Grant [P30-CA023074]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA023074, P01CA109552] Funding Source: NIH RePORTER	This work was supported by National Institutes of Health grant P01-CA109552 (DVH) and the University of Arizona Cancer Center Support Core Grant P30-CA023074	Beroza P, 2005, CURR TOP MED CHEM, V5, P371, DOI 10.2174/1568026053828394; Boujrad H, 2007, CELL CYCLE, V6, P2612, DOI 10.4161/cc.6.21.4842; Buolamwini JK, 2005, CURR CANCER DRUG TAR, V5, P57, DOI 10.2174/1568009053332672; Capdeville R, 2002, NAT REV DRUG DISCOV, V1, P493, DOI 10.1038/nrd839; Da Violante G, 2002, BIOL PHARM BULL, V25, P1600, DOI 10.1248/bpb.25.1600; Druker BJ, 1996, NAT MED, V2, P561, DOI 10.1038/nm0596-561; Henderson MC, 2009, MOL CANCER THER, V8, P36, DOI 10.1158/1535-7163.MCT-08-0789; Hong OY, 2000, AM J PATHOL, V157, P1623, DOI 10.1016/S0002-9440(10)64800-6; Jaffee EM, 2002, CANCER CELL, V2, P25, DOI 10.1016/S1535-6108(02)00093-4; Jemal A, 2005, CA-CANCER J CLIN, V55, P10, DOI 10.3322/canjclin.55.1.10; Jones S, 2008, SCIENCE, V321, P1801, DOI 10.1126/science.1164368; Maiuri MC, 2007, NAT REV MOL CELL BIO, V8, P741, DOI 10.1038/nrm2239; Miyaki M, 2003, BIOCHEM BIOPH RES CO, V306, P799, DOI 10.1016/S0006-291X(03)01066-0; MOSMANN T, 1983, J IMMUNOL METHODS, V65, P55, DOI 10.1016/0022-1759(83)90303-4; OKABE T, 1983, CANCER, V51, P662, DOI 10.1002/1097-0142(19830215)51:4<662::AID-CNCR2820510419>3.0.CO;2-X; Pourpak A, 2007, INVEST NEW DRUG, V25, P107, DOI 10.1007/s10637-006-9015-6; REERS M, 1991, BIOCHEMISTRY-US, V30, P4480, DOI 10.1021/bi00232a015; Roth BL, 1997, APPL ENVIRON MICROB, V63, P2421, DOI 10.1128/AEM.63.6.2421-2431.1997; SMILEY ST, 1991, P NATL ACAD SCI USA, V88, P3671, DOI 10.1073/pnas.88.9.3671; Sohn TA, 2001, ANN SURG, V233, P696, DOI 10.1097/00000658-200105000-00014; Stephens B, 2008, MOL CANCER THER, V7, P202, DOI 10.1158/1535-7163.MCT-07-0542; Susin SA, 1999, NATURE, V397, P441, DOI 10.1038/17135; Tascilar M, 2001, CLIN CANCER RES, V7, P4115; Wang H, 2006, CANCER RES, V66, P9722, DOI 10.1158/0008-5472.CAN-05-4602; Zhou SB, 1998, P NATL ACAD SCI USA, V95, P2412, DOI 10.1073/pnas.95.5.2412	25	1	1	0	10	SPRINGER	DORDRECHT	VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS	0167-6997	1573-0646		INVEST NEW DRUG	Invest. New Drugs	JUN	2013	31	3					576	586		10.1007/s10637-012-9901-z			11	Oncology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	140MA	WOS:000318657000009	23179338	Green Accepted			2022-04-25	
J	Yang, F; Peng, ZX; Ji, WD; Yu, JD; Qian, C; Liu, JD; Fang, GE				Yang, Feng; Peng, Zhang-xiao; Ji, Wei-dan; Yu, Ju-dian; Qian, Chen; Liu, Jian-dong; Fang, Guo-en			LncRNA CCAT1 Upregulates ATG5 to Enhance Autophagy and Promote Gastric Cancer Development by Absorbing miR-140-3p	DIGESTIVE DISEASES AND SCIENCES			English	Article; Early Access						Gastric cancer; Autophagy; LncRNA CCAT1; miR-140-3p; ATG5	NONCODING RNA CCAT1; C-MYC; PROGRESSION	Background Long noncoding RNA colon cancer-associated transcript 1 (LncRNA CCAT1) is highly expressed in gastric cancer tissues and plays a role in autophagy. However, the underlying mechanism still needs to be further clarified. Objective To study the role of LncRNA CCAT1 in regulating autophagy of gastric cancer cells, analyze its downstream targets, and elucidate the mechanism. Methods qPCR detected the expression of LncRNA CCAT1 in gastric cancer cells. The proliferation, migration, and invasion ability of LncRNA CCAT1 and the expression level of autophagy-related proteins in gastric cancer cells were detected. Bioinformatics method predicted the downstream targets of LncRNA CCAT1, and they were verified by dual-luciferase assay. The relationship between LncRNA CCAT1, miR-140, and ATG5 was verified by co-transfection, and the expression levels of ATG5 and ATG5-ATG12 complex proteins were detected. Finally, the role of LncRNA CCAT1 in vivo was confirmed by gastric cancer transplantation model. Results LncRNA CCAT1 was highly expressed in gastric cancer cells. LncRNA CCAT1 can promote the proliferation, migration, invasion, and autophagy activity of gastric cancer cells. LncRNA CCAT1 can bind to miR-140-3p and regulate its expression, while miR-140-3p further regulates the expression of ATG5. Overexpression of LncRNA CCAT1 can promote tumor growth in nude mice. After LncRNA CCAT1 silencing, the positive expression rate of ATG5 in nude mice was low. Conclusion LncRNA CCAT1 may inhibit the expression of miR-140-3p by sponge adsorption, thus weakening its inhibitory effect on ATG5. Eventually, gastric cancer cells were more prone to autophagy under the pressure of stress.	[Yang, Feng; Yu, Ju-dian; Qian, Chen; Liu, Jian-dong] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Gen Surg, Shanghai 201805, Peoples R China; [Peng, Zhang-xiao; Ji, Wei-dan] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Mol Tumor Lab, Shanghai 201805, Peoples R China; [Fang, Guo-en] Second Mil Med Univ, Changhai Hosp, Dept Gen Surg, 68 Changhai Rd, Shanghai 200433, Peoples R China		Fang, GE (corresponding author), Second Mil Med Univ, Changhai Hosp, Dept Gen Surg, 68 Changhai Rd, Shanghai 200433, Peoples R China.	fangguoen56@163.com			Shanghai Municipal Health and Family Planning Commission [201840070]; Science and Technology Commission of Jiading District, Shanghai [JDKW-2018-W12]	This study was supported by the subject of Shanghai Municipal Health and Family Planning Commission (general project) (No. 201840070) and the subject of Science and Technology Commission of Jiading District, Shanghai (No. JDKW-2018-W12).	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Dis. Sci.												10.1007/s10620-021-07187-9		AUG 2021	17	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	UD2AD	WOS:000687014600002	34417924				2022-04-25	
J	Mimura, K; Sakamaki, JI; Morishita, H; Kawazu, M; Mano, H; Mizushima, N				Mimura, Kaito; Sakamaki, Jun-Ichi; Morishita, Hideaki; Kawazu, Masahito; Mano, Hiroyuki; Mizushima, Noboru			Genome-wide CRISPR screening reveals nucleotide synthesis negatively regulates autophagy	JOURNAL OF BIOLOGICAL CHEMISTRY			English	Article							HOPS COMPLEX; COLON-CANCER; 5-FLUOROURACIL; GROWTH; IDENTIFICATION; CHEMOTHERAPY; METABOLISM; REPRESSION; INHIBITION; RECEPTOR	Macroautophagy (hereafter, autophagy) is a process that directs the degradation of cytoplasmic material in lysosomes. In addition to its homeostatic roles, autophagy undergoes dynamic positive and negative regulation in response to multiple forms of cellular stress, thus enabling the survival of cells. However, the precise mechanisms of autophagy regulation are not fully understood. To identify potential negative regulators of autophagy, we performed a genome-wide CRISPR screen using the quantitative autophagic flux reporter GFP-LC3-RFP. We identified phosphoribosylformylglycinamidine synthase, a component of the de novo purine synthesis pathway, as one such negative regulator of autophagy. Autophagy was activated in cells lacking phosphoribosylformylglycinamidine synthase or phosphoribosyl pyrophosphate amidotransferase, another de novo purine synthesis enzyme, or treated with methotrexate when exogenous levels of purines were insufficient. Purine starvation-induced autophagy activation was concomitant with mammalian target of rapamycin complex 1 (mTORC1) suppression and was profoundly suppressed in cells deficient for tuberous sclerosis complex 2, which negatively regulates mTORC1 through inhibition of Ras homolog enriched in brain, suggesting that purines regulate autophagy through the tuberous sclerosis complex-Ras homolog enriched in brainm-TORC1 signaling axis. Moreover, depletion of the pyrimidine synthesis enzymes carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase and dihydroorotate dehydrogenase activated autophagy as well, although mTORC1 activity was not altered by pyrimidine shortage. These results suggest a different mechanism of autophagy induction between purine and pyrimidine starvation. These findings provide novel insights into the regulation of autophagy by nucleotides and possibly the role of autophagy in nucleotide metabolism, leading to further developing anticancer strategies involving nucleotide synthesis and autophagy.	[Mimura, Kaito; Sakamaki, Jun-Ichi; Morishita, Hideaki; Mizushima, Noboru] Univ Tokyo, Grad Sch, Dept Biochem & Mol Biol, Tokyo, Japan; [Mimura, Kaito; Sakamaki, Jun-Ichi; Morishita, Hideaki; Mizushima, Noboru] Univ Tokyo, Fac Med, Tokyo, Japan; [Kawazu, Masahito; Mano, Hiroyuki] Natl Canc Ctr, Div Cellular Signaling, Tokyo, Japan; [Morishita, Hideaki] Juntendo Univ, Dept Physiol, Grad Sch Med, Tokyo 1138421, Japan		Mizushima, N (corresponding author), Univ Tokyo, Grad Sch, Dept Biochem & Mol Biol, Tokyo, Japan.; Mizushima, N (corresponding author), Univ Tokyo, Fac Med, Tokyo, Japan.	nmizu@m.u.tokyo.ac.jp	Mizushima, Noboru/C-3635-2009; Kawazu, Masahito/AAE-6143-2022	Mizushima, Noboru/0000-0002-6258-6444; Kawazu, Masahito/0000-0003-4146-3629; Morishita, Hideaki/0000-0003-0860-8371; Mimura, Kaito/0000-0002-0053-0218	Japan Science and Technology AgencyJapan Science & Technology Agency (JST) [JPMJER1702]; MD Scientist Training Program, Faculty of Medicine, The University of Tokyo	This work was supported by a grant for Exploratory Research for Advanced Technology from the Japan Science and Technology Agency (JPMJER1702 to N. M.). K. M. was supported by the MD Scientist Training Program, Faculty of Medicine, The University of Tokyo.	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Biol. Chem.	JAN-JUN	2021	296								100780	10.1016/j.jbc.2021.100780			13	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	TL2WM	WOS:000674717300002	34000301	gold, Green Published			2022-04-25	
J	Calvo-Martin, G; Plano, D; Encio, I; Sanmartin, C				Calvo-Martin, Gorka; Plano, Daniel; Encio, Ignacio; Sanmartin, Carmen			Novel N,N '-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents	ANTIOXIDANTS			English	Article						selenoureas; antioxidant; cytotoxicity; radical scavenging; selenium	CELL-CYCLE ARREST; BIOLOGICAL EVALUATION; IN-VITRO; ANTIPROLIFERATIVE AGENTS; ANTICANCER ACTIVITY; CANCER; DERIVATIVES; SELENIUM; APOPTOSIS; FERROCENE	A series of 30 novel N,N disubstituted selenoureas were synthesized, characterized, and their antioxidant ability was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2 '-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assays. Additionally, their cytotoxic activity was tested in vitro in a panel of three different cancer (breast, lung and colon) and two normal cell lines. Each selenourea entity contains a para-substituted phenyl ring with different electron-withdrawing and electron-donating groups, and different aliphatic and aromatic nuclei. All of the synthesized selenoureas present antioxidant capacity at high concentrations in the DPPH assay, and three of them (2b, 2c and 2d) showed greater radical scavenging capacity than ascorbic acid at lower concentrations. These results were confirmed by the ABTS assay, where these novel selenoureas present even higher antioxidant capacity than the reference compound Trolox. On the other hand, 10 selenoureas present IC50 values below 10 mu M in at least one cancer cell line, resulting in the adamantyl nucleus (6a-6e), the most interesting in terms of activity and selectivity. Outstanding results were found for selenourea 6c, tested in the NCI60 cell line panel and showing an average GI(50) of 1.49 mu M for the 60 cell lines, and LC50 values ranging from 9.33 mu M to 4.27 mu M against 10 of these cancer cell lines. To gain insight into its anticancer activity mechanism, we investigated the cell cycle progression of the promising compound 6c, as well as the type of programmed-cell death in a colon cancer cell line it provokes (HT-29). Compound 6c provoked S phase cell cycle arrest and the induction of cell death was independent of caspase activation, suggesting autophagy, though this assertion requires additional studies. Overall, we envision that this compound can be further developed for the potential treatment of colon cancer.	[Calvo-Martin, Gorka; Plano, Daniel; Sanmartin, Carmen] Univ Navarra, Dept Tecnol & Quim Farmaceut, Irunlarrea 1, E-31008 Pamplona, Spain; [Calvo-Martin, Gorka; Plano, Daniel; Encio, Ignacio; Sanmartin, Carmen] Inst Invest Sanit Navarra IdiSNA, Irunlarrea 3, E-31008 Pamplona, Spain; [Encio, Ignacio] Univ Publ Navarra, Dept Ciencias Salud, Avda Baranain S-N, E-31008 Pamplona, Spain		Sanmartin, C (corresponding author), Univ Navarra, Dept Tecnol & Quim Farmaceut, Irunlarrea 1, E-31008 Pamplona, Spain.; Sanmartin, C (corresponding author), Inst Invest Sanit Navarra IdiSNA, Irunlarrea 3, E-31008 Pamplona, Spain.	gcalvo.3@alumni.unav.es; dplano@unav.es; ignacio.encio@unavarra.es; sanmartin@unav.es	Plano, Daniel/K-3001-2014; Sanmartin, Carmen/K-1188-2014	Plano, Daniel/0000-0002-8266-0445; Encio, Ignacio/0000-0003-1732-1989; Sanmartin, Carmen/0000-0003-3431-7826; Calvo-Martin, Gorka/0000-0003-2806-5183	PIUNA [2014-26, 2018-19]; UNED-Caja Navarra Fundacion La Caixa	This research was funded by PIUNA (refs 2014-26 and 2018-19) and UNED-Caja Navarra Fundacion La Caixa.	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J	Goossens, JF; Bailly, C				Goossens, Jean-Francois; Bailly, Christian			Ursodeoxycholic acid and cancer: From chemoprevention to chemotherapy	PHARMACOLOGY & THERAPEUTICS			English	Review						Ursodeoxycholic acid; Bile acids; Anticancer drug; Hepatocellular carcinoma; Drug design	NF-KAPPA-B; EPITHELIAL-MESENCHYMAL TRANSITION; HEPATOCELLULAR-CARCINOMA CELLS; PRIMARY SCLEROSING CHOLANGITIS; DERIVATIVES INDUCE APOPTOSIS; INFLAMMATORY-BOWEL-DISEASE; PRIMARY BILIARY-CIRRHOSIS; RECEPTOR GPBAR1 TGR5; PROTEIN-KINASE-C; BILE-ACID	Ursodeoxycholic acid (UDCA) is a secondary bile acid issued from the transformation of (cheno)deoxycholic acid by intestinal bacteria, acting as a key regulator of the intestinal barrier integrity and essential for lipid metabolism. UDCA is also a long-established drug, largely used for the dissolution of cholesterol gallstones, the treatment of primary biliary cholangitis and other hepatobiliary disorders. The history of UDCA is briefly retraced here as well as its multifactorial mechanism of action, based on its anti-inflammatory, antioxidant and cytoprotective activities. The present review is centred around the anticancer properties of UDCA and synthetic antitumor derivatives designed over the past 20 years. Paradoxically, depending on the conditions, UDCA exhibits both pro- and anti-apoptotic properties toward different cell types. In particular, the UDCA drug can protect epithelial cells from damages and apoptosis while inducing inhibition of proliferation and apoptotic and/or autophagic death of cancer cells. The effects of UDCA on cancer cell migration, cancer stem cells and drug-induced dysbiosis are also evoked. The drug has revealed modest activities against colon and gastric cancers but may be useful to improve treatments of hepatocellular carcinoma, notably in combination with other drugs such as sorafenib. UDCA can also protect from damages induced by cancer chemotherapeutic agents. The potential of UDCA in cancer, as a chemo-protecting or chemotherapeutic agent, is highlighted here as well as the design of tumour-active derivatives, including UDCA-drug conjugates. A repurposing of UDCA in oncology should be further considered. (C) 2019 Elsevier Inc. All rights reserved.	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Ther.	NOV	2019	203								107396	10.1016/j.pharmthera.2019.107396			13	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	JO0ZL	WOS:000497315100009	31356908				2022-04-25	
J	Frank, D; Vaux, DL; Murphy, JM; Vince, JE; Lindqvist, LM				Frank, Daniel; Vaux, David L.; Murphy, James M.; Vince, James E.; Lindqvist, Lisa M.			Activated MLKL attenuates autophagy following its translocation to intracellular membranes	JOURNAL OF CELL SCIENCE			English	Article						Necroptosis; Autophagy; MLKL; LC3	MIXED LINEAGE KINASE; DOMAIN-LIKE; CELL-DEATH; MEDIATES NECROPTOSIS; FAMILY-MEMBERS; PROTEIN; PHOSPHORYLATION; NECROSIS; TNF; DOWNSTREAM	Necroptosis is an inflammatory form of programmed cell death mediated by the pseudokinase mixed-lineage kinase domain-like protein (MLKL). Upon phosphorylation by receptor-interacting protein kinase-3 (RIPK3), MLKL oligomerizes, and translocates to and disrupts the plasma membrane, thereby causing necroptotic cell lysis. Herein, we show that activation of necroptosis in mouse dermal fibroblasts (MDFs) and HT-29 human colorectal cancer cells results in accumulation of the autophagic marker, lipidated LC3B (also known as MAP1LC3B), in an MLKL-dependent manner. Unexpectedly, the necroptosis-induced increase in lipidated LC3B was due to inhibition of autophagic flux, not the activation of autophagy. Inhibition of autophagy by MLKL correlated with a decrease in autophagosome and/or autolysosome function, and required the association of activated MLKL with intracellular membranes. Collectively, our findings uncover an additional role for the MLKL pseudokinase, namely to inhibit autophagy during necroptosis.	[Frank, Daniel; Vaux, David L.; Murphy, James M.; Lindqvist, Lisa M.] Walter & Eliza Hall Inst Med Res, Cell Signalling & Cell Death Div, 1G Royal Parade, Melbourne, Vic 3052, Australia; [Frank, Daniel; Vaux, David L.; Murphy, James M.; Vince, James E.; Lindqvist, Lisa M.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3050, Australia; [Vince, James E.] Walter & Eliza Hall Inst Med Res, Inflammat Div, 1G Royal Parade, Melbourne, Vic 3052, Australia; [Lindqvist, Lisa M.] CSL Ltd, Res & Clin Bioanalyt, 30 Flemington Rd, Parkville, Vic 3052, Australia		Lindqvist, LM (corresponding author), Walter & Eliza Hall Inst Med Res, Cell Signalling & Cell Death Div, 1G Royal Parade, Melbourne, Vic 3052, Australia.; Vince, JE; Lindqvist, LM (corresponding author), Univ Melbourne, Dept Med Biol, Parkville, Vic 3050, Australia.; Vince, JE (corresponding author), Walter & Eliza Hall Inst Med Res, Inflammat Div, 1G Royal Parade, Melbourne, Vic 3052, Australia.; Lindqvist, LM (corresponding author), CSL Ltd, Res & Clin Bioanalyt, 30 Flemington Rd, Parkville, Vic 3052, Australia.	vince@wehi.edu.au; Lisa.Lindqvist@csl.com.au	Vaux, David L/C-7249-2013	Vaux, David L/0000-0003-2703-1651; vince, james/0000-0001-7166-2798; Frank, Daniel/0000-0003-4998-2220	Australian National Health and Medical Research Council (NHMRC)National Health and Medical Research Council (NHMRC) of Australia [461221, 1101405, 1145788]; NHMRCNational Health and Medical Research Council (NHMRC) of Australia [1105754, 1141466, 1020136, 361646]; Melbourne Research Scholarship (MRS); Victorian State Government Operational Infrastructure Support Grant	This work was supported by Australian National Health and Medical Research Council (NHMRC) Program 461221 (D.L.V.), and Project 1101405 (J.E.V.) and 1145788 (J.M.M., J.E.V. and L.M.L.) grants. J.M.M. (1105754) and J.E.V. (1141466) were supported by NHMRC Career Development Fellowships, while D.L.V. held an NHMRC Fellowship (1020136). D.F. was supported by Melbourne Research Scholarship (MRS). This work was also made possible through an Independent Research Institutes Infrastructure Support Scheme Grant (361646) from the NHMRC and a Victorian State Government Operational Infrastructure Support Grant.	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Cell Sci.	MAR	2019	132	5							jcs220996	10.1242/jcs.220996			11	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	HP1GO	WOS:000461414300010	30709919	Bronze			2022-04-25	
J	Zheng, HC				Zheng, Hua-Chuan			The molecular mechanisms of chemoresistance in cancers	ONCOTARGET			English	Review						cancer; chemoresistance; molecular mechanisms; chemotherapy	EPITHELIAL-MESENCHYMAL TRANSITION; CELL-LIKE PROPERTIES; BREAST-CANCER; CONFERS CHEMORESISTANCE; DRUG-RESISTANCE; DOWN-REGULATION; REGULATES CHEMORESISTANCE; COLON-CANCER; LUNG-CANCER; STEM-CELLS	Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-kappa B), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome. Their cross-talk frequently appears, such as the regulatory effects of EGFR-Akt-NF-kappa B signal pathway on the transcription of Bcl-2, Bcl-xL and survivin or EMT-related stemness. It is essential for the realization of the target, individualized and combine therapy to clarify these molecular mechanisms, explore the therapy target, screen chemosensitive population, and determine the efficacy of chemoreagents by cell culture and orthotopic model.	[Zheng, Hua-Chuan] China Med Univ, Dept Expt Oncol, Shengjing Hosp, Shenyang 110004, Peoples R China; [Zheng, Hua-Chuan] China Med Univ, Anim Ctr, Shengjing Hosp, Shenyang 110004, Peoples R China		Zheng, HC (corresponding author), China Med Univ, Dept Expt Oncol, Shengjing Hosp, Shenyang 110004, Peoples R China.; Zheng, HC (corresponding author), China Med Univ, Anim Ctr, Shengjing Hosp, Shenyang 110004, Peoples R China.	zheng_huachuan@hotmail.com			Liaoning BaiQianWan Talents Program; Key Scientific and Technological Project of Liaoning Province [2015408001]; National Natural Scientific Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472544, 81672700]; Award for Liaoning Distinguished Professor	This study was supported by Liaoning BaiQianWan Talents Program, Award for Liaoning Distinguished Professor, A Key Scientific and Technological Project of Liaoning Province (2015408001), and National Natural Scientific Foundation of China (81472544; 81672700).	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Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	FF4RD	WOS:000408941900171	28938696	Green Published, gold	Y	N	2022-04-25	
J	Li, ZW; Zhuang, M; Zhang, LC; Zheng, XN; Yang, P; Li, ZY				Li, Zongwei; Zhuang, Ming; Zhang, Lichao; Zheng, Xingnan; Yang, Peng; Li, Zhuoyu			Acetylation modification regulates GRP78 secretion in colon cancer cells	SCIENTIFIC REPORTS			English	Article							PROTEIN LYSINE ACETYLATION; TUMOR MICROENVIRONMENT; EXTRACELLULAR VESICLES; EXOSOMES; MICROVESICLES; ACTIVATION; AUTOPHAGY; VPS34; FIBROBLASTS; PROGRESSION	High glucose-regulated protein 78 (GRP78) expression contributes to the acquisition of a wide range of phenotypic cancer hallmarks, and the pleiotropic oncogenic functions of GRP78 may result from its diverse subcellular distribution. Interestingly, GRP78 has been reported to be secreted from solid tumour cells, participating in cell-cell communication in the tumour microenvironment. However, the mechanism underlying this secretion remains elusive. Here, we report that GRP78 is secreted from colon cancer cells via exosomes. Histone deacetylase (HDAC) inhibitors blocked GRP78 release by inducing its aggregation in the ER. Mechanistically, HDAC inhibitor treatment suppressed HDAC6 activity and led to increased GRP78 acetylation; acetylated GRP78 then bound to VPS34, a class III phosphoinositide-3 kinase, consequently preventing the sorting of GRP78 into multivesicular bodies (MVBs). Of note, we found that mimicking GRP78 acetylation by substituting the lysine at residue 633, one of the deacetylated sites of HDAC6, with a glutamine resulted in decreased GRP78 secretion and impaired tumour cell growth in vitro. Our study thus reveals a hitherto-unknown mechanism of GRP78 secretion and may also provide implications for the therapeutic use of HDAC inhibitors.	[Li, Zongwei; Zhang, Lichao; Yang, Peng; Li, Zhuoyu] Shanxi Univ, Inst Biotechnol, Key Lab Chem Biol & Mol Engn, Natl Minist Educ, Taiyuan 030006, Peoples R China; [Li, Zongwei] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Div Canc Med, Ctr Canc Immunol Res, Houston, TX 77030 USA; [Zhuang, Ming] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Gen Surg, Shanghai 200092, Peoples R China; [Zheng, Xingnan] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA		Li, ZY (corresponding author), Shanxi Univ, Inst Biotechnol, Key Lab Chem Biol & Mol Engn, Natl Minist Educ, Taiyuan 030006, Peoples R China.	lzy@sxu.edu.cn	Li, Zongwei/AAM-4135-2021		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31201072, 31271516]; Shanxi Province Science Foundation for Outstanding Youths [201601D021007]; Zhejiang Province Science Foundation [LY15H280008]	This study was supported by the National Natural Science Foundation of China (No. 31201072, No. 31271516), the Shanxi Province Science Foundation for Outstanding Youths (201601D021007), and the Zhejiang Province Science Foundation (LY15H280008).	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J	Yun, S; Han, YS; Lee, JH; Kim, S; Lee, SH				Yun, Seungpil; Han, Yong-Seok; Lee, Jun Hee; Kim, Sangmin; Lee, Sang Hun			Enhanced Susceptibility to 5-Fluorouracil in Human Colon Cancer Cells by Silencing of GRP78	ANTICANCER RESEARCH			English	Article						Colon cancer; 5-FU; GRP78; ER stress; apoptosis	ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; ER STRESS; HEPATOCELLULAR-CARCINOMA; HEME OXYGENASE-1; PROSTATE-CANCER; ROS; AUTOPHAGY; HYDROETHIDINE; ACTIVATION	Background: Glucose-regulated protein (GRP78), also known as immunoglobulin heavy chain binding protein and as heat shock 70 kDa protein 5, is present in the endoplasmic reticulum (ER) membrane. GRP78 is generally expressed at low concentrations, but is increased by physiological stress. GRP78 is thought to protect against tissue or organ damage under pathological conditions, such as neurotoxic stress, myocardial infarction, or arteriosclerosis. In addition, in tumors, GRP78 expression is much higher than in normal tissues. Furthermore, high levels of GRP78 expression have been shown to increase the risk of malignancy and metastasis in prostate and colon cancer. Because both anticancer drugs and down-regulation of GRP78 expression inhibit cancer progression and growth, we hypothesized that down-regulation of GRP78 expression might lead to enhanced susceptibility of cancer cells to cytotoxic action of 5-fluorouracil (5-FU). Materials and Methods: GRP78 expression was suppressed in LoVo colon cancer cells by utilizing small-interfering RNA (si-GRP78), and the cells were subsequently used to study the antiproliferative and anticancer effects of 5-FU treatment. The signaling pathways responsible for the increase of LoVo cell susceptibility to 5-FU treatment after exposure to GRP78 siRNA were determined by western blot. Results: GRP78 silencing significantly inhibited cell viability and increased apoptosis of LoVo cells. Furthermore, combined treatment with 5-FU and GRP78 siRNA for 12 h reduced cell viability, and increased apoptosis and generation reactive oxygen species more strongly than either of the two treatments applied separately. In order to examine the role of ER stress in increased susceptibility of LoVo cells to 5-FU after pretreatment with GRP78 siRNA, we analyzed expression levels of ER stress marker proteins, such as phosphorylated protein kinase-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic initiation factor 2 alpha (eIF2 alpha), activating transcription factor 4 (ATF4), phosphorylated inositol-requiring enzyme 1 alpha (IRE1 alpha), phosphorylated p38, and C/EBP homologous protein (CHOP). Treatment with 5-FU alone increased the expression of ER stress marker proteins, whereas combined exposure to both 5-FU and GRP78 siRNA led to an even stronger effect on these markers. Similar to the pattern of modulation of ER stress protein expression, the levels of apoptosis-related proteins were also more strongly affected by combined exposure to 5-FU and GRP78 siRNA than by single treatments. In particular, expression of Bcl-2-associated X protein (BAX), cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase 1 (PARP1) were increased, whereas the expression of B-cell lymphoma 2 (BCL2) was reduced by these treatments. Conclusion: GRP78 silencing and incubation with 5-FU have synergistic effects on the inhibition of LoVo colon cancer cell growth via the induction of ER stress-dependent apoptosis.	[Yun, Seungpil; Kim, Sangmin] Johns Hopkins Univ, Sch Med, Dept Neurol, Neuroregenerat & Stem Cell Programs,Inst Cell Eng, Baltimore, MD 21205 USA; [Han, Yong-Seok; Lee, Sang Hun] Soonchunhyang Univ, Seoul Hosp, Med Sci Res Inst, Seoul, South Korea; [Han, Yong-Seok; Lee, Sang Hun] Soonchunhyang Univ, Dept Med Biosci, Asan, South Korea; [Lee, Jun Hee] Univ Alabama Birmingham, Birmingham Sch Med, Dept Pharmacol & Toxicol, Birmingham, AL USA		Lee, SH (corresponding author), Soonchunhyang Univ, Soonchunhyang Med Sci Res Inst, Seoul Hosp, 59 Daesagwan Ro,657 Hannam Dong, Seoul 140887, South Korea.	jhlee0407@sch.ac.kr; ykckss1114@nate.com	lee, sang hun/Q-4650-2019	lee, sang hun/0000-0002-9005-5966	Soonchunhyang University; National Research Foundation grant - Korean governmentNational Research Foundation of Korea [NRF-2016R1D1A3B01007727]; Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea [HI14C2253]	This study was supported by the Soonchunhyang University Research Fund, a National Research Foundation grant funded by the Korean government (NRF-2016R1D1A3B01007727), and a grant from the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI14C2253). The funders had no role in study design, data collection or analysis, decision to publish, or preparation of the article.	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JUN	2017	37	6					2975	2984		10.21873/anticanres.11651			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EW0LG	WOS:000402181600025	28551635	Bronze			2022-04-25	
J	Walker, T; Mitchell, C; Park, MA; Yacoub, A; Graf, M; Rahmani, M; Houghton, PJ; Voelkel-Johnson, C; Grant, S; Dent, P				Walker, Teneille; Mitchell, Clint; Park, Margaret A.; Yacoub, Adly; Graf, Martin; Rahmani, Mohamed; Houghton, Peter J.; Voelkel-Johnson, Christina; Grant, Steven; Dent, Paul			Sorafenib and Vorinostat Kill Colon Cancer Cells by CD95-Dependent and -Independent Mechanisms	MOLECULAR PHARMACOLOGY			English	Article							HISTONE DEACETYLASE INHIBITOR; HUMAN-LEUKEMIA-CELLS; SUBEROYLANILIDE HYDROXAMIC ACID; PRIMARY RODENT HEPATOCYTES; SIGNAL-REGULATED KINASE; INDUCED APOPTOSIS; DOWN-REGULATION; TUMOR-CELLS; HEPATOCELLULAR-CARCINOMA; SYNERGISTIC INTERACTIONS	We examined the interaction between the multikinase inhibitor sorafenib and histone deacetylase inhibitors. Sorafenib and vorinostat synergized ( sorafenib + vorinostat) to kill HCT116 and SW480 cells. In SW480 cells, sorafenib + vorinostat increased CD95 plasma membrane levels and promoted death-inducing signal complex ( DISC) formation, and drug toxicity was blocked by knockdown of CD95 or overexpression of cellular FLICE-like inhibitory protein (c-FLIP-s). In SW620 cells that are patient-matched to SW480 cells, sorafenib + vorinostat toxicity was significantly lower, which correlated with a lack of CD95 activation and lower expression of ceramide synthase 6 (LASS6). Overexpression of LASS6 in SW620 cells enhanced drug-induced CD95 activation and enhanced tumor cell killing, whereas knockdown of LASS6 in SW480 cells suppressed CD95 activation. Knocking down LASS6 expression also suppressed CD95 activation in hepatoma, pancreatic, and ovarian cancer cells. In HCT116 cells, sorafenib + vorinostat treatment caused DISC formation without reducing c-FLIP-s expression and did not increase CD95 plasma membrane levels; sorafenib + vorinostat exposure killed HCT116 cells via an intrinsic pathway/caspase 9-dependent mechanism. In HCT116 cells, knockdown of CD95 enhanced sorafenib + vorinostat lethality, which correlated with less drug-induced CD95-dependent autophagy. Sorafenib + vorinostat treatment activated the c-Jun NH2-terminal kinase pathway, which was causal in promoting dissociation of Beclin1 from BCL-2, and in promoting autophagy. Knockdown of Beclin1 expression blocked autophagy and enhanced drug toxicity. Our data demonstrate that treatment of colon cancer cells with sorafenib + vorinostat activates CD95 via de novo ceramide synthesis that promotes viability via autophagy or degrades survival via either the extrinsic or intrinsic pathways.	[Walker, Teneille; Mitchell, Clint; Park, Margaret A.; Grant, Steven; Dent, Paul] Virginia Commonwealth Univ, Dept Biochem, Richmond, VA 23298 USA; [Rahmani, Mohamed; Grant, Steven] Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA; [Yacoub, Adly] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA 23298 USA; [Graf, Martin] Virginia Commonwealth Univ, Dept Neurosurg, Richmond, VA 23298 USA; [Grant, Steven; Dent, Paul] Virginia Commonwealth Univ, Inst Mol Med, Richmond, VA 23298 USA; [Voelkel-Johnson, Christina] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA; [Houghton, Peter J.] St Jude Childrens Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA		Dent, P (corresponding author), Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Massey Canc Ctr, 401 Coll St,Room 280A,Box 980035, Richmond, VA 23298 USA.	pdent@vcu.edu		Rahmani, Mohamed/0000-0002-3992-8039	NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA063753, P01CA104177, R01CA108520, R01CA093738] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01DK052825] Funding Source: NIH RePORTER; NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01-CA108520, R01-CA77141, P01-CA104177, R01-CA93738, R01-CA63753, R01 CA093738] Funding Source: Medline; NIDDK NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01-DK52825, R01 DK052825] Funding Source: Medline		Allan LA, 2003, NAT CELL BIOL, V5, P647, DOI 10.1038/ncb1005; Bali P, 2005, CLIN CANCER RES, V11, P6382, DOI 10.1158/1078-0432.CCR-05-0344; Barnhart BC, 2003, SEMIN IMMUNOL, V15, P185, DOI 10.1016/S1044-5323(03)00031-9; Dasmahapatra G, 2007, CLIN CANCER RES, V13, P4280, DOI 10.1158/1078-0432.CCR-07-0835; 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Park MA, 2008, MOL PHARMACOL, V73, P1168, DOI 10.1124/mol.107.042697; Parkin DM, 2005, CA-CANCER J CLIN, V55, P74, DOI 10.3322/canjclin.55.2.74; Portanova P, 2008, INT J ONCOL, V33, P325, DOI 10.3892/ijo_00000012; Qiao L, 2003, MOL CELL BIOL, V23, P3052, DOI 10.1128/MCB.23.9.3052-3066.2003; Qiao L, 2002, HEPATOLOGY, V35, P779, DOI 10.1053/jhep.2002.32533; Qiao L, 2001, MOL BIOL CELL, V12, P2629, DOI 10.1091/mbc.12.9.2629; Rahmani M, 2005, J BIOL CHEM, V280, P35217, DOI 10.1074/jbc.M506551200; Rahmani M, 2007, MOL PHARMACOL, V72, P788, DOI 10.1124/mol.106.033308; Rahmani M, 2007, MOL CELL BIOL, V27, P5499, DOI 10.1128/MCB.01080-06; Rini BI, 2006, EXPERT OPIN PHARMACO, V7, P453, DOI 10.1517/14656566.7.4.453; Strumberg D, 2005, DRUGS TODAY, V41, P773, DOI 10.1358/dot.2005.41.12.937959; Valerie K, 2007, MOL CANCER THER, V6, P789, DOI 10.1158/1535-7163.MCT-06-0596; Venturelli S, 2007, CANCER, V109, P2132, DOI 10.1002/cncr.22652; Wang YJ, 2008, J BIOL CHEM, V283, P4766, DOI 10.1074/jbc.M706666200; Wang YF, 2007, CLIN CANCER RES, V13, P4934, DOI 10.1158/1078-0432.CCR-07-0665; Wei YJ, 2008, MOL CELL, V30, P678, DOI 10.1016/j.molcel.2008.06.001; White-Gilbertson S, 2009, ONCOGENE, V28, P1132, DOI 10.1038/onc.2008.468; Wise LD, 2007, BIRTH DEFECTS RES B, V80, P57, DOI 10.1002/bdrb.20104; Yacoub A, 2008, MOL CANCER THER, V7, P297, DOI 10.1158/1535-7163.MCT-07-2166; Yu C, 2005, LEUKEMIA, V19, P1579, DOI 10.1038/sj.leu.2403868; Yu CR, 2003, CANCER BIOL THER, V2, P544, DOI 10.4161/cbt.2.5.454; Zhang G, 2008, CLIN CANCER RES, V14, P5385, DOI 10.1158/1078-0432.CCR-08-0469	54	69	74	0	10	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS	BETHESDA	9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA	0026-895X	1521-0111		MOL PHARMACOL	Mol. Pharmacol.	AUG	2009	76	2					342	355		10.1124/mol.109.056523			14	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	472SV	WOS:000268153400011	19483104	Green Published			2022-04-25	
J	Cai, XM; Wei, B; Li, LL; Chen, XF; Yang, J; Li, XF; Jiang, XZ; Lv, M; Li, MY; Lin, YM; Xu, Q; Guo, WJ; Gu, YH				Cai, Xiaomin; Wei, Bin; Li, Lele; Chen, Xiaofeng; Yang, Jing; Li, Xiaofei; Jiang, Xiaozheng; Lv, Mu; Li, Mingyang; Lin, Yumeng; Xu, Qiang; Guo, Wenjie; Gu, Yanhong			Therapeutic Potential of Apatinib Against Colorectal Cancer by Inhibiting VEGFR2-Mediated Angiogenesis and beta-Catenin Signaling	ONCOTARGETS AND THERAPY			English	Article						apatinib; colorectal cancer; VEGFR2; angiogenesis; beta-catenin	STEM-CELLS; COLON; ACTIVATION; APOPTOSIS; AUTOPHAGY; DRIVEN; PLUS	Purpose: Apatinib is an inhibitor of VEGFR2 (vascular endothelial growth factor receptor 2) that has attracted a great deal of attention due to its promotion of anticancer activity. In the present study, we investigated the therapeutic effects of apatinib against colorectal cancer (CRC) and examined the underlying mechanism. Materials and Methods: Both in vivo and in vitro assays were conducted to study the effect of apatinib on CRC. To elucidate the associated mechanism, RNA-seq (transcriptome) analysis was conducted on apatinib-treated HCT116 cells. Results: Apatinib showed antiproliferative and proapoptotic effects, induced G0/G1 arrest and blocked cell migration and invasion in CRC. An analysis of the mechanism associated with apatinib activity demonstrated that by interacting with VEGFR2, apatinib decreased p-Src, p-Akt, and p-GSK3 beta levels, which further increased beta-catenin ubiquitination and reduced the nuclear translocation of beta-catenin. Furthermore, apatinib strongly suppressed CT26 cell growth in mouse xenograft models by inhibiting beta-catenin signaling and angiogenesis. Conclusion: Overall, the results of the present study here indicated that by inhibiting the VEGFR2-beta-catenin-mediated malignant phenotype, apatinib significantly suppresses the growth of CRC, suggesting that the use of apatinib is a promising therapeutic strategy for CRC.	[Cai, Xiaomin; Wei, Bin; Li, Lele; Chen, Xiaofeng; Yang, Jing; Li, Xiaofei; Jiang, Xiaozheng; Lv, Mu; Li, Mingyang; Gu, Yanhong] Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, 300 Guangzhou Rd, Nanjing 210029, Peoples R China; [Wei, Bin] Nanjing Med Univ, Affiliated Huaian 1 Peoples Hosp, Dept Oncol, Huaian 223300, Peoples R China; [Lin, Yumeng; Xu, Qiang; Guo, Wenjie] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, 163 Xianlin Ave, Nanjing 210023, Peoples R China		Gu, YH (corresponding author), Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, 300 Guangzhou Rd, Nanjing 210029, Peoples R China.; Guo, WJ (corresponding author), Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, 163 Xianlin Ave, Nanjing 210023, Peoples R China.	guowj@nju.edu.cn; guyhphd@163.com					Bekaii-Saab T, 2019, CLIN COLORECTAL CANC, V18, pE117, DOI 10.1016/j.clcc.2018.11.002; Beurel E, 2015, PHARMACOL THERAPEUT, V148, P114, DOI 10.1016/j.pharmthera.2014.11.016; Cai XM, 2020, INT IMMUNOPHARMACOL, V88, DOI 10.1016/j.intimp.2020.106858; Chen X, 2019, ONCOLOGIST, V24; Chen YNP, 2016, NATURE, V535, P148, DOI 10.1038/nature18621; Cheng X, 2018, CANCER LETT, V431, P105, DOI 10.1016/j.canlet.2018.05.046; Cheng XF, 2019, BIOMED PHARMACOTHER, V110, P473, DOI 10.1016/j.biopha.2018.11.082; Feng RM, 2019, CANCER COMMUN, V39, DOI 10.1186/s40880-019-0368-6; Geng J, 2019, BRIT J PHARMACOL, V176, P4574, DOI 10.1111/bph.14823; Geng RX, 2015, EXPERT OPIN PHARMACO, V16, P117, DOI 10.1517/14656566.2015.981526; Guo W, 2017, NAT COMMUN, V8, P1, DOI DOI 10.1038/S41467-017-00911-Y; Guo WJ, 2013, AUTOPHAGY, V9, P996, DOI 10.4161/auto.24407; Guo WJ, 2014, AUTOPHAGY, V10, P972, DOI 10.4161/auto.28374; Hankey W, 2018, CANCER RES, V78, P617, DOI 10.1158/0008-5472.CAN-17-1357; Huang JQ, 2017, SCI REP-UK, V7, DOI 10.1038/srep40716; Huang MP, 2018, BMC GASTROENTEROL, V18, DOI 10.1186/s12876-018-0870-3; Ji QB, 2019, NAT COMMUN, V10, DOI 10.1038/s41467-018-08277-5; Jope RS, 2003, TRENDS PHARMACOL SCI, V24, P441, DOI 10.1016/S0165-6147(03)00206-2; Kelly H, 2005, J CLIN ONCOL, V23, P4553, DOI 10.1200/JCO.2005.17.749; Keum N, 2019, NAT REV GASTRO HEPAT, V16, P713, DOI 10.1038/s41575-019-0189-8; Le DT, 2015, NEW ENGL J MED, V372, P1; Lee M, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0028454; Li J, 2015, LANCET ONCOL, V16, P619, DOI 10.1016/S1470-2045(15)70156-7; Li J, 2013, J CLIN ONCOL, V31, P3219, DOI 10.1200/JCO.2013.48.8585; Liao Y, 2014, BIOINFORMATICS, V30, P923, DOI 10.1093/bioinformatics/btt656; Liu KS, 2017, CELL DEATH DIS, V8, DOI 10.1038/cddis.2017.422; Luo MN, 2016, CANCER LETT, V373, P1, DOI 10.1016/j.canlet.2016.01.010; Maes C, 2010, EMBO J, V29, P424, DOI 10.1038/emboj.2009.361; Marcus L, 2017, CLIN CANCER RES, V23, P2924, DOI 10.1158/1078-0432.CCR-16-2157; Morin PJ, 1999, BIOESSAYS, V21, P1021, DOI 10.1002/(SICI)1521-1878(199912)22:1<1021::AID-BIES6>3.0.CO;2-P; Muzny DM, 2012, NATURE, V487, P330, DOI 10.1038/nature11252; Nusse R, 2017, CELL, V169, P985, DOI 10.1016/j.cell.2017.05.016; Overman MJ, 2018, J CLIN ONCOL, V36, P773, DOI 10.1200/JCO.2017.76.9901; Qian YY, 2019, SCI ADV, V5, DOI 10.1126/sciadv.aaw6710; Raji RJ, 2018, BIOSYSTEMS, V172, P26, DOI 10.1016/j.biosystems.2018.08.001; Reya T, 2005, NATURE, V434, P843, DOI 10.1038/nature03319; Sanchez-Gundin J, 2018, INT J MED SCI, V15, P659, DOI 10.7150/ijms.24453; Scott AJ, 2015, DRUG TODAY, V51, P223, DOI 10.1358/dot.2015.51.4.2320599; Shirley M, 2018, DRUGS, V78, P1757, DOI 10.1007/s40265-018-0998-z; Siegel RL, 2020, CA-CANCER J CLIN, V70, P145, DOI 10.3322/caac.21601; Tampellini M, 2017, CLIN COLORECTAL CANC, V16, P372, DOI 10.1016/j.clcc.2017.03.019; Tejeda-Munoz N, 2015, IUBMB LIFE, V67, P914, DOI 10.1002/iub.1454; Vermeulen L, 2010, NAT CELL BIOL, V12, P468, DOI 10.1038/ncb2048; Wu L, 2017, IRAN J BASIC MED SCI, V20, P990, DOI 10.22038/IJBMS.2017.9263; Yang JL, 2012, EXP EYE RES, V100, P101, DOI 10.1016/j.exer.2012.03.011; Yin Liang, 2017, Nan Fang Yi Ke Da Xue Xue Bao, V37, P367; Yu XY, 2020, ONCOL LETT, V20, DOI 10.3892/ol.2020.11913; Zhang HJ, 2015, DRUG DES DEV THER, V9, P6075, DOI 10.2147/DDDT.S97235	48	3	3	1	3	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1178-6930			ONCOTARGETS THER	OncoTargets Ther.		2020	13						11031	11044		10.2147/OTT.S266549			14	Biotechnology & Applied Microbiology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	OH7TG	WOS:000582795800017	33154652	Green Published, gold			2022-04-25	
J	Gao, C; Cao, WP; Bao, L; Zuo, W; Xie, GM; Cai, TT; Fu, W; Zhang, J; Wu, W; Zhang, X; Chen, YG				Gao, Chan; Cao, Weipeng; Bao, Lan; Zuo, Wei; Xie, Guoming; Cai, Tiantian; Fu, Wei; Zhang, Jian; Wu, Wei; Zhang, Xu; Chen, Ye-Guang			Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation	NATURE CELL BIOLOGY			English	Article							TUMOR-SUPPRESSOR PROTEIN; REQUIRES DIRECT BINDING; CATENIN PATHWAY; BETA-CATENIN; UBIQUITINATION; GENE; TUMORIGENESIS; LIGASE; INHIBITION; ACTIVATION	In eukaryotic cells, autophagy is a highly conserved self-digestion process to promote cell survival in response to nutrient starvation and other metabolic stresses. Autophagy is regulated by cell signalling such as the mTOR (mammalian target of rapamycin) pathway. However, the significance of autophagy in modulation of signal transduction is unclear. Here we show that autophagy negatively regulates Wnt signalling by promoting Dishevelled (Dvl) degradation. Von Hippel-Lindau protein-mediated ubiquitylation is critical for the binding of Dvl2 to p62, which in turn facilitates the aggregation and the LC3-mediated autophagosome recruitment of Dvl2 under starvation; the ubiquitylated Dvl2 aggregates are ultimately degraded through the autophagy-lysosome pathway. Moreover, a reverse correlation between Dvl expression and autophagy is observed in late stages of colon cancer development, indicating that autophagy may contribute to the aberrant activation of Wnt signalling in tumour formation.	[Gao, Chan; Cao, Weipeng; Zuo, Wei; Xie, Guoming; Chen, Ye-Guang] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China; [Gao, Chan; Cao, Weipeng; Zuo, Wei; Xie, Guoming; Cai, Tiantian; Wu, Wei; Chen, Ye-Guang] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China; [Bao, Lan; Zhang, Xu] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China; [Fu, Wei] Peking Univ, Hosp 3, Dept Gen Surg, Beijing 100191, Peoples R China; [Zhang, Jian] Chinese Acad Sci, Inst Genet & Dev Biol, Beijing 100101, Peoples R China		Chen, YG (corresponding author), Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.	ygchen@tsinghua.edu.cn	Gao, Chan/D-7964-2013; Chen, Ye-Guang/L-6998-2019		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [30930050, 30921004]; 973 ProgramNational Basic Research Program of China [2006CB943401, 2010CB833706]	We thank Terje Johansen for p62 constructs, Long Yu for human LC3 construct, Noboru Mizushima for Atg5<SUP>-/-</SUP> MEFs, Masaaki Komatsu for Atg7<SUP>-/-</SUP> MEFs, and Li Yu, Rod Nusse, Daniel J. Klionsky, Juan Liang and Zhao Chen for suggestions. This work was supported by grants from the National Natural Science Foundation of China (30930050 and 30921004) and the 973 Program (2006CB943401 and 2010CB833706) to Y.-G.C.	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Cell Biol.	AUG	2010	12	8					781	+		10.1038/ncb2082			20	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	634EF	WOS:000280561600010	20639871				2022-04-25	
J	Sequeira, D; Baptista, PV; Valente, R; Piedade, MFM; Garcia, MH; Morais, TS; Fernandes, AR				Sequeira, Diogo; Baptista, Pedro V.; Valente, Ruben; Piedade, M. Fatima M.; Garcia, M. Helena; Morais, Tania S.; Fernandes, Alexandra R.			Cu(I) complexes as new antiproliferative agents against sensitive and doxorubicin resistant colorectal cancer cells: synthesis, characterization, and mechanisms of action	DALTON TRANSACTIONS			English	Article								Cancer is one of the worst health issues worldwide, representing the second leading cause of death. Current chemotherapeutic drugs face some challenges like the acquired resistance of the tumoral cells and low specificity leading to unwanted side effects. There is an urgent need to develop new compounds that may target resistant cells. The synthesis and characterization of two Cu(I) complexes of general formula [Cu(PP)(LL)][BF4], where PP is a phosphane ligand (triphenylphosphine or 1,2-bis(diphenylphosphano) ethane) and LL = is a heteroaromatic bidentate ligand (4,4'-dimethyl-2,2'-bipyridine and 6,3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine). The new compounds were fully characterized by spectroscopic techniques (NMR, FTIR and UV-vis.), elemental analysis (C, H, N and S) and two structures were determined by single X-ray diffraction studies. The antiproliferative potential of the new Cu(I) complexes were studied in tumor (breast adenocarcinoma, ovarian carcinoma and in colorectal carcinoma sensitive and resistant to doxorubicin) and normal (fibroblasts) cell lines. Complexes 1-4 did not show any antiproliferative potential. Amongst the complexes 5-8, complex 8 shows high cytotoxic potential against colorectal cancer sensitive and resistant to doxorubicin and low cytotoxicity towards healthy cells. We show that complexes 5-8 can cleave pDNA and, in particular, the in vitro pDNA cleavage is due to an oxidative mechanism. This oxidative mechanism corroborates the induction of reactive oxygen species (ROS), that triggers HCT116 cell death via apoptosis, as proved by the increased expression of BAX protein relative to BCL-2 protein and the depolarization of mitochondrial membrane potential, and via autophagy. Additionally, complex 8 can block the cell cycle in the G1 phase, also exhibiting a cytostatic potential. Proteomic analysis confirmed the apoptotic, autophagic and cytostatic potential of complex 8, as well as its ability to produce ROS and cause DNA damage. The interference of the complex in folding and protein synthesis and its ability to cause post-translational modifications was also verified. Finally, it was observed that the complex causes a reduction in cellular metabolism. The results herein demonstrated the potential of Cu(I) complexes in targeting doxorubicin sensitive and resistant cells which is positive and must be further explored using in vivo animal models.	[Sequeira, Diogo; Baptista, Pedro V.; Valente, Ruben; Fernandes, Alexandra R.] Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Ciencias Vida, UCIBIO, Lisbon, Portugal; [Piedade, M. Fatima M.; Garcia, M. Helena; Morais, Tania S.] Univ Lisbon, Fac Ciencias, Dept Quim & Bioquim, DQB FCUL, Lisbon, Portugal; [Piedade, M. Fatima M.] Univ Lisbon, Inst Super Tecn, Ctr Quim Estrutural, CCQE IST, Lisbon, Portugal; [Garcia, M. Helena; Morais, Tania S.] Univ Lisbon, Fac Ciencias, Ctr Quim Estrutural, CQE FCUL, Lisbon, Portugal		Fernandes, AR (corresponding author), Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Ciencias Vida, UCIBIO, Lisbon, Portugal.; Morais, TS (corresponding author), Univ Lisbon, Fac Ciencias, Dept Quim & Bioquim, DQB FCUL, Lisbon, Portugal.; Morais, TS (corresponding author), Univ Lisbon, Fac Ciencias, Ctr Quim Estrutural, CQE FCUL, Lisbon, Portugal.	tsmorais@ciencias.ulisboa.pt; ma.fernandes@fct.unl.pt	Morais, Tânia S./D-8824-2011; Garcia, Maria Helena/H-2175-2013; Fernandes, Alexandra/C-7465-2011; Baptista, Pedro/A-1237-2009	Morais, Tânia S./0000-0003-0233-8243; Garcia, Maria Helena/0000-0002-4344-2218; Valente, Ruben/0000-0001-6534-4128; Fernandes, Alexandra/0000-0003-2054-4438; Baptista, Pedro/0000-0001-5255-7095	Applied Molecular Biosciences Unit - UCIBIO - FCT [UIDB/04378/2020]; Centro de Quimica Estrutural - FCT [UIDB/00100/2020]; FCTPortuguese Foundation for Science and TechnologyEuropean Commission [CEECIND/00630/2017]	This work was supported by the Applied Molecular Biosciences Unit - UCIBIO and Centro de Quimica Estrutural which are financed by national funds from FCT (UIDB/04378/2020 and UIDB/00100/2020, respectively). T. S. Morais thanks FCT for CEECIND 2017 Initiative for the project CEECIND/00630/2017 (acknowledging FCT, as well as POPH and FSE-European Social Fund). M. Silva and C. Fonseca are also acknowledged for preliminary fluorescence microscopy and viability data, respectively.	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FEB 7	2021	50	5					1845	1865		10.1039/d0dt03566a			21	Chemistry, Inorganic & Nuclear	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	QE6SV	WOS:000616337100034	33470993				2022-04-25	
J	Rong, L; Li, ZD; Leng, X; Li, HY; Ma, YP; Chen, YK; Song, FZ				Rong, Li; Li, Zhaodong; Leng, Xue; Li, Haiyu; Ma, Yongping; Chen, Yaokai; Song, Fangzhou			Salidroside induces apoptosis and protective autophagy in human gastric cancer AGS cells through the PI3K/Akt/mTOR pathway	BIOMEDICINE & PHARMACOTHERAPY			English	Article						Salidroside; Gastric cancer; Apoptosis; Autophagy; PI3K/AKT/mTOR	MTOR PATHWAY; DISEASE; CHINA	Salidroside, a natural active ingredient extracted from Rhodiola rosea, has been shown to exert antitumor activity against breast cancer Dong Young et al. [1], colon cancer Sun et al. [2] and bladder cancer Tian et al. [3]. However, the effect of salidroside on apoptosis and autophagy in gastric cancer remains unclear. In our research, we observed the biological effect of salidroside on human gastric cancer AGS cells. Our results demonstrated that salidroside inhibited the growth of AGS cells both in vivo and in vitro and exerted a proapoptotic effect on AGS cells as confirmed by flow cytometry, Hoechst staining and western blot analysis. Additionally, we found that salidroside decreased the phosphorylation of PI3K and Akt and that pretreatment with the PI3K/Akt agonist IGF-1 could weaken the proapoptotic effect of salidroside. Interestingly, the exposure of AGS cells to salidroside induced autophagy as indicated by transmission electron microscopy, mRFP-GFP-LC3 transfection and western blot analysis, suggesting that salidroside promoted autophagy in gastric cancer AGS cells. Furthermore, treatment with the autophagy inhibitor chloroquine enhanced salidroside-induced cell apoptosis, indicating that the autophagy mediated by salidroside may protect AGS cells from death. Additionally, we found that salidroside decreased the level of p-mTOR protein in a concentration-dependent manner and that pretreatment with IGF-1 decreased the expression of autophagy proteins, suggesting that salidroside induced autophagy through the PI3K/Akt/mTOR pathway. The above findings indicate that salidroside inhibited the growth of gastric cancer and induced apoptosis and protective autophagy through the PI3K/Akt/mTOR pathway. In summary, our study provides novel insights regarding the activity of salidroside against gastric cancer and contributes to the clinical application of salidroside combined with autophagy inhibitors as a chemotherapeutic strategy for human gastric cancer.	[Rong, Li; Li, Zhaodong; Leng, Xue; Li, Haiyu; Ma, Yongping; Song, Fangzhou] Chongqing Med Univ, Basic Med Coll, 1 Med Coll Rd, Chongqing 400016, Peoples R China; [Rong, Li; Li, Haiyu; Chen, Yaokai] Chongqing Publ Hlth Med Ctr, 109 Baoyu Rd, Chongqing 400036, Peoples R China		Song, FZ (corresponding author), Chongqing Med Univ, Basic Med Coll, 1 Med Coll Rd, Chongqing 400016, Peoples R China.; Chen, YK (corresponding author), Chongqing Publ Hlth Med Ctr, 109 Baoyu Rd, Chongqing 400036, Peoples R China.	l3883886491@163.com; 19702119@qq.com; 904561548@qq.com; lihaiyu@stu.cqmu.edu.cn; 93404551@qq.com; yaokaichen@hotmail.com; fzsongcq@163.com		Song, Fang/0000-0002-4083-3889	TCM Science and Technology Project of Chongqing Health and Family Planning Commission [ZY201702048]; Chongqing natural science foundationNatural Science Foundation of Chongqing [cstc2019jcyj-msxmX0428]; National Science and Technology Major Project of China [2018ZX10302104]	1. TCM Science and Technology Project of Chongqing Health and Family Planning Commission, Project number: ZY201702048.; 2. Chongqing natural science foundation, Project number:cstc2019jcyj-msxmX0428; 3. The National Science and Technology Major Project of China during the 13th five-year plan period. Project number: 2018ZX10302104.	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Pharmacother.	FEB	2020	122								109726	10.1016/j.biopha.2019.109726			9	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	KA7VF	WOS:000506005800044	31918283	gold			2022-04-25	
J	Liu, J; Zhang, Y; Qu, JL; Xu, L; Hou, KZ; Zhang, JD; Qu, XJ; Liu, YP				Liu, Jing; Zhang, Ye; Qu, Jinglei; Xu, Ling; Hou, Kezuo; Zhang, Jingdong; Qu, Xiujuan; Liu, Yunpeng			beta-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis	BMC CANCER			English	Article							MAMMALIAN TARGET; COLON-CANCER; TUMOR-CELLS; P38 MAPK; DEATH; INHIBITION; ACTIVATION; PI3K/AKT; ANTIBODY; THERAPY	Background: beta-Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anti-cancer effects against a broad spectrum of tumors. The mechanism by which beta elemene kills cells remains unclear. The aim of the present study is to investigate the anti-tumor effect of beta-elemene on human gastric cancer cells and the molecular mechanism involved. Results: beta-Elemene inhibited the viability of human gastric cancer MGC803 and SGC7901 cells in a dose-dependent manner. The suppression of cell viability was due to the induction of apoptosis. A robust autophagy was observed in the cells treated with beta-elemene; it was characterized by the increase of punctate LC3 dots, the cellular morphology, and the increased levels of LC3 II protein. Further study showed that beta elemene treatment up-regulated Atg5-Atg12 conjugated protein but had little effect on other autophagy-related proteins. PI3K/Akt/mTOR/p70S6K1 activity was inhibited by beta-elemene. Knockdown of Beclin 1 with small interfering RNA, or co-treatment with the autophagy inhibitor, 3-methyladenine or chlorochine enhanced significantly the antitumor effects of beta-elemene. Conclusions: Our data provides the first evidence that beta-elemene induces protective autophagy and prevents human gastric cancer cells from undergoing apoptosis. A combination of beta-elemene with autophagy inhibitor might thus be a useful therapeutic option for advanced gastric cancer.	[Liu, Jing; Zhang, Ye; Qu, Jinglei; Xu, Ling; Hou, Kezuo; Zhang, Jingdong; Qu, Xiujuan; Liu, Yunpeng] China Med Univ, Hosp 1, Dept Med Oncol, Shenyang 110001, Peoples R China		Qu, XJ (corresponding author), China Med Univ, Hosp 1, Dept Med Oncol, Shenyang 110001, Peoples R China.	qu_xiujuan2001@yahoo.co.jp; cmuliuyunpeng@yahoo.cn			Chinese National Foundation of National Sciences [30770993]; China Postdoctor Foundation of Science [20070411081]; The First Hospital of China Medical University [fsfh1002]; CSCO-King Kong Elemene	YL (Chinese National Foundation of National Sciences grants 30770993); XQ (China Postdoctor Foundation of Science grants 20070411081); JL (Fund for Scientific Research of The First Hospital of China Medical University, fsfh1002); YZ (The Doctor Startup Fund Program Funded by CSCO-King Kong Elemene).	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J	Zuo, Q; Liao, L; Yao, ZT; Liu, YP; Wang, DK; Li, SJ; Yin, XF; He, QY; Xu, WW				Zuo, Qian; Liao, Long; Yao, Zi-Ting; Liu, Ya-Ping; Wang, Ding-Kang; Li, Shu-Jun; Yin, Xing-Feng; He, Qing-Yu; Xu, Wen-Wen			Targeting PP2A with lomitapide suppresses colorectal tumorigenesis through the activation of AMPK/Beclin1-mediated autophagy	CANCER LETTERS			English	Article						Lomitapide; Colorectal cancer; PP2A inhibitor; AMPK; Autophagy	CANCER; CARCINOMA; AMPK; ASSOCIATION; INHIBITION; MODULATION; APOPTOSIS; PATHWAY; CELLS; MAP	Colorectal cancer (CRC) is one of the most common malignancies worldwide, and effective therapy remains a challenge. In this study, we take advantage of a drug repurposing strategy to screen small molecules with novel anticancer activities in a small-molecule library consisting of 1056 FDA-approved drugs. We show, for the first time, that lomitapide, a lipid-lowering agent, exhibits antitumor properties in vitro and in vivo. Activated autophagy is characterized as a key biological process in lomitapide-induced CRC repression. Mechanistically, lomitapide stimulated mitochondrial dysfunction-mediated AMPK activation, resulting in increased AMPK phosphorylation and enhanced Beclin1/Atg14/Vps34 interactions, provoking autophagy induction. Autophagy inhibition or AMPK silencing significantly abrogated lomitapide-induced cell death, indicating the significance of AMPK-regulated autophagy in the antitumor activities of lomitapide. More importantly, PP2A was identified as a direct target of lomitapide by limited proteolysis-mass spectrometry (LiP-SMap), and the bioactivity of lomitapide was attenuated in PP2A-deficient cells, suggesting that the anticancer effect of lomitapide occurs in a PP2Adependent manner. Taken together, the results of the study reveal that lomitapide can be repositioned as a potential therapeutic drug for CRC treatment.	[Zuo, Qian; Liao, Long; Yao, Zi-Ting; Liu, Ya-Ping; Wang, Ding-Kang; Li, Shu-Jun; Yin, Xing-Feng; He, Qing-Yu] Jinan Univ, Coll Life Sci & Technol, Inst Life & Hlth Engn, MOE Key Lab Tumor Mol Biol, Guangzhou 510632, Peoples R China; [Zuo, Qian; Liao, Long; Yao, Zi-Ting; Liu, Ya-Ping; Wang, Ding-Kang; Li, Shu-Jun; Yin, Xing-Feng; He, Qing-Yu] Jinan Univ, Coll Life Sci & Technol, Inst Life & Hlth Engn, Key Lab Funct Prot Res Guangdong Higher Educ Inst, Guangzhou 510632, Peoples R China; [Xu, Wen-Wen] Jinan Univ, Coll Life Sci & Technol, Natl Engn Res Ctr Genet Med, Inst Biomed,MOE Key Lab Tumor Mol Biol, Guangzhou 510632, Peoples R China; [Xu, Wen-Wen] Jinan Univ, Coll Life Sci & Technol, Natl Engn Res Ctr Genet Med, Inst Biomed,Guangdong Prov Key Lab Bioengn Med, Guangzhou 510632, Peoples R China		Xu, WW (corresponding author), Jinan Univ, Natl Engn Res Ctr Genet Med, Inst Biomed, Guangdong Prov Key Lab Bioengn Med, Guangzhou 510632, Peoples R China.	xuwen6966@163.com			National Natural Science Foundation of China of ChinaNational Natural Science Foundation of China (NSFC) [82073196, 81803551, 31770888]; National Key R&D Program of China [2017YFA0505100]; Guangdong Natural Science Research Grant International joint project [2021A0505030035]; Guangdong Natural Science Research Grant [2021A1515011158, 2020A1515110760]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [21620429]	This research was supported by National Natural Science Foundation of China of China (82073196, 81803551, 31770888) , National Key R&D Program of China (2017YFA0505100) , Guangdong Natural Science Research Grant International joint project (2021A0505030035) , Guangdong Natural Science Research Grant (2021A1515011158, 2020A1515110760) , and the Fundamental Research Funds for the Central Universities (21620429) .	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J	Krmpot, AJ; Janjetovic, KD; Misirkic, MS; Vucicevic, LM; Pantelic, DV; Vasiljevic, DM; Popadic, DM; Jelenkovic, BM; Trajkovic, VS				Krmpot, Aleksandar J.; Janjetovic, Kristina D.; Misirkic, Maja S.; Vucicevic, Ljubica M.; Pantelic, Dejan V.; Vasiljevic, Darko M.; Popadic, Dusan M.; Jelenkovic, Branislav M.; Trajkovic, Vladimir S.			Protective Effect of Autophagy in Laser-Induced Glioma Cell Death In Vitro	LASERS IN SURGERY AND MEDICINE			English	Article						apoptosis; cancer; necrosis; phototherapy	TUMOR-NECROSIS-FACTOR; COLORECTAL LIVER METASTASES; PHOTODYNAMIC THERAPY; INDUCED APOPTOSIS; CANCER-CELLS; MAMMALIAN-CELLS; PKC ACTIVATION; IRRADIATION; PROLIFERATION; THERMOTHERAPY	Background and Objective: Laser phototherapy could be potentially used for cancer treatment, but the mechanisms of laser-induced cell death are not completely understood. Autophagy is the process in which the damaged cellular proteins and organelles are engulfed by and destroyed in acidified multiple-membrane vesicles. The aim of the present study was to investigate the role of autophagy in laser-induced tumor cell death in vitro. Study Design/Materials and Methods: The monolayers of U251 human glioma tumor cells were exposed to 532 nm laser light from a single mode frequency-doubled Nd-YVO4 laser. A flattened Gaussian radial profile of laser beam (0.5-4W) was used to uniformly illuminate entire colony of cells for various amounts of time (15-120 seconds) in the absence of cell culture medium. The cells were grown for 24 hours and the cell viability was determined by crystal violet or MTT assay. The presence of autophagy was assessed after 16 hours by fluorescence microscopy/flow cytometric analysis of acridine orange-stained autophagolysosomes and Western blot analysis of the autophagosome-associated LC3-II protein. The concentration of the principal pro-autophagic protein beclin-1 was determined after 6 hours by cell-based ELISA. Results: The intracytoplasmic accumulation of autophagic vesicles, increase in LC3-II and up-regulation of beclin-1 expression were clearly observed under irradiation conditions that caused approximately 50% cytotoxicity. Postirradiation addition of three different autophagy inhibitors (bafilomycin A1, chloroquine, or wortmannin) further increased the laser-induced cytotoxicity, without affecting non-irradiated cells. Conclusions: These data indicate that beclin-1-dependent induction of autophagy can protect glioma cells from laser-mediated cytotoxicity. Lasers Surg. Med. 42:338-347, 2010. (C) 2010 Wiley-Liss, Inc.	[Janjetovic, Kristina D.; Misirkic, Maja S.; Vucicevic, Ljubica M.; Popadic, Dusan M.; Trajkovic, Vladimir S.] Univ Belgrade, Sch Med, Inst Microbiol & Immunol, Belgrade 11000, Serbia; [Krmpot, Aleksandar J.; Pantelic, Dejan V.; Vasiljevic, Darko M.; Jelenkovic, Branislav M.] Univ Belgrade, Inst Phys, Belgrade 11080, Serbia; [Janjetovic, Kristina D.; Misirkic, Maja S.; Vucicevic, Ljubica M.; Popadic, Dusan M.] Inst Biol Res, Belgrade 11000, Serbia		Trajkovic, VS (corresponding author), Univ Belgrade, Sch Med, Inst Microbiol & Immunol, Dr Subotica 1, Belgrade 11000, Serbia.	krmpot@phy.bg.ac.rs; vtrajkovic@eunet.rs	Jelenkovic, Brana/AAE-8831-2020; Vasiljević, Darko/R-8265-2019; Krmpot, Aleksandar/C-4975-2011; Vasiljević, Darko/ABA-3894-2020	Vasiljević, Darko/0000-0001-6737-6000; Misirkic Marjanovic, Maja/0000-0002-0510-826X; Krmpot, Aleksandar/0000-0003-2751-7395; Janjetovic, Kristina/0000-0003-1387-480X; Vucicevic, Ljubica/0000-0003-2802-2773; Popadic, Dusan/0000-0002-7502-1709; Trajkovic, Vladimir/0000-0002-8061-2968	Ministry of Science of the Republic of SerbiaMinistry of Education, Science & Technological Development, Serbia [145073, 141003]	Contract grant sponsor: Ministry of Science of the Republic of Serbia; Contract grant numbers: 145073, 141003.	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J	Ortiz, LMG; Lombardi, P; Tillhon, M; Scovassi, AI				Ortiz, Luis Miguel Guaman; Lombardi, Paolo; Tillhon, Micol; Scovassi, Anna Ivana			Berberine, an Epiphany Against Cancer	MOLECULES			English	Review						apoptosis; autophagy; berberine; cancer; traditional medicine	ACTIVATED PROTEIN-KINASE; DNA TOPOISOMERASE-I; INDUCED GROWTH-INHIBITION; LEUKEMIA HL-60 CELLS; INDUCED APOPTOSIS; DOWN-REGULATION; ALKALOID BERBERINE; CARCINOMA-CELLS; COLON-CANCER; LUNG-CANCER	Alkaloids are used in traditional medicine for the treatment of many diseases. These compounds are synthesized in plants as secondary metabolites and have multiple effects on cellular metabolism. Among plant derivatives with biological properties, the isoquinoline quaternary alkaloid berberine possesses a broad range of therapeutic uses against several diseases. In recent years, berberine has been reported to inhibit cell proliferation and to be cytotoxic towards cancer cells. Based on this evidence, many derivatives have been synthesized to improve berberine efficiency and selectivity; the results so far obtained on human cancer cell lines support the idea that they could be promising agents for cancer treatment. The main properties of berberine and derivatives will be illustrated.	[Ortiz, Luis Miguel Guaman; Tillhon, Micol; Scovassi, Anna Ivana] Ist Genet Mol CNR, I-27100 Pavia, Italy; [Ortiz, Luis Miguel Guaman] Univ Tecn Particular Loja, Dept Ciencias Salud, Calle Paris 1101608, Loja, Ecuador; [Lombardi, Paolo] Naxospharma, I-20026 Novate Milanese, Italy		Scovassi, AI (corresponding author), Ist Genet Mol CNR, Via Abbiategrasso 207, I-27100 Pavia, Italy.	lmguaman@utpl.edu.ec; p.lombardi@naxospharma.eu; tillhon@igm.cnr.it; scovassi@igm.cnr.it	Ortiz, Luis Miguel Guaman/X-9496-2019; Tillhon, Micol/AAQ-6994-2020	Ortiz, Luis Miguel Guaman/0000-0003-2919-4905; Lombardi, Paolo/0000-0002-7971-7404; Scovassi, Anna Ivana/0000-0003-3484-9881	SENESCYT (Quito, Ecuador); Universidad Tecnica Particular de Loja (Loja, Ecuador); Italian AIRCFondazione AIRC per la ricerca sul cancro	LMGO is a PhD student (Dottorato in Genetica, Biologia Cellulare e Molecolare, University of Pavia, Italy) supported by SENESCYT (Quito, Ecuador) and Universidad Tecnica Particular de Loja (Loja, Ecuador); MT is a post-doc supported by Italian AIRC. The authors acknowledge Lucrezia Lombardi for English revision of the text.	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J	Deng, YL; Li, S; Wang, M; Chen, XT; Tian, L; Wang, LQ; Yang, WY; Chen, LZ; He, F; Yin, WY				Deng, Yuanle; Li, Sha; Wang, Meng; Chen, Xiaotong; Tian, Li; Wang, Liqun; Yang, Wenyu; Chen, Lezhang; He, Fang; Yin, Wenya			Flavonoid-rich extracts from okra flowers exert antitumor activity in colorectal cancer through induction of mitochondrial dysfunction-associated apoptosis, senescence and autophagy	FOOD & FUNCTION			English	Article							CELL-PROLIFERATION; COLON-CANCER; P53; INVASION; METASTASIS; POLYMORPHISMS; MORTALITY; MIGRATION; SURVIVAL; MMP-2	Okra flowers contain a higher content of total flavonoids than most other flowers; however little research has been conducted on their potential benefits, including antitumor activity. In this study, we extracted and purified flavonoids from okra flower (AFE), and aimed to evaluate the effect of AFE and its underlying mechanism on colorectal cancer (CRC) cell growth in vitro and in vivo. Here, we identify that AFE is a safe, natural antioxidant and exerts significant antitumor efficacy on the inhibition of CRC cell proliferation and metastasis as well as tumour growth in vivo. We further reveal that AFE inhibits CRC cell proliferation by inducing mitochondrial dysfunction, which results from the activation of p53 and induction of apoptosis and senescence, and inhibits autophagic degradation. Furthermore, AFE inhibited migration and invasion of CRC cells by regulating the balance of MMP2/TIMP2 and MMP9 expression levels. Of note, administration of AFE as a preventive agent achieves a more effective antitumor effect than the therapeutic agent in a xenograft mouse model. Our results reveal, for the first time, that AFE is a safe, natural antioxidant with significant antitumor efficacy, which has great potential in the application for CRC prevention and treatment.	[Deng, Yuanle; Li, Sha; Chen, Xiaotong; Tian, Li; Wang, Liqun; He, Fang; Yin, Wenya] Sichuan Univ, West China Sch Publ Hlth, Chengdu 610041, Sichuan, Peoples R China; [Deng, Yuanle; Li, Sha; Chen, Xiaotong; Tian, Li; Wang, Liqun; He, Fang; Yin, Wenya] Sichuan Univ, West China Hosp 4, Chengdu 610041, Sichuan, Peoples R China; [Wang, Meng; Yang, Wenyu] Xihua Univ, Sch Food Sci & Bioengn, Pharmaceut Engn, Chengdu 610039, Sichuan, Peoples R China; [Chen, Lezhang] Sichuan Huitai Agr Technol Co LTD, Chengdu, Peoples R China		He, F; Yin, WY (corresponding author), Sichuan Univ, West China Sch Publ Hlth, Chengdu 610041, Sichuan, Peoples R China.; He, F; Yin, WY (corresponding author), Sichuan Univ, West China Hosp 4, Chengdu 610041, Sichuan, Peoples R China.	hf18602880124@163.com; yinwenya@scu.edu.cn		Yin, Wenya/0000-0001-7698-6871; Deng, Yuanle/0000-0002-5748-585X			Acosta JC, 2012, TRENDS CELL BIOL, V22, P211, DOI 10.1016/j.tcb.2011.11.006; Alfadda AA, 2012, J BIOMED BIOTECHNOL, DOI 10.1155/2012/936486; Arnold M, 2017, GUT, V66, P683, DOI 10.1136/gutjnl-2015-310912; Beckerman R., 2010, COLD SPRING HARB PER, V2, P8; Bosetti C, 2011, EUR J CANCER PREV, V20, P355, DOI 10.1097/CEJ.0b013e32834653c9; Bray F., 2015, CANC DIS CONTROL PRI, V3, DOI [10.1596/978-1-4648-0349-9_ch2, DOI 10.1596/978-1-4648-0349-9_CH2]; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Calon A, 2012, CANCER CELL, V22, P571, DOI 10.1016/j.ccr.2012.08.013; Center MM, 2009, CA-CANCER J CLIN, V59, P366, DOI 10.3322/caac.20038; Chaemsawang W, 2019, INT J BIOMATER, V2019, DOI 10.1155/2019/9404383; Chang H, 2018, NUTRIENTS, V10, DOI 10.3390/nu10070950; Chernov AV, 2009, J BIOL CHEM, V284, P12727, DOI 10.1074/jbc.M900273200; Cyjon A, 2001, BRIT J CANCER, V85, P504, DOI 10.1054/bjoc.2001.1972; Demain AL, 2011, MICROB BIOTECHNOL, V4, P687, DOI 10.1111/j.1751-7915.2010.00221.x; Favoriti P, 2016, UPDATES SURG, V68, P7, DOI 10.1007/s13304-016-0359-y; FEARON ER, 1990, CELL, V61, P759, DOI 10.1016/0092-8674(90)90186-I; Friedl P, 2003, NAT REV CANCER, V3, P362, DOI 10.1038/nrc1075; Fu R, 2019, J AGR FOOD CHEM, V67, P4808, DOI 10.1021/acs.jafc.9b00833; Gimenez-Bastida JA, 2019, MOL NUTR FOOD RES, V63, DOI 10.1002/mnfr.201900629; Han CZ, 2018, ONCOL LETT, V15, P4463, DOI 10.3892/ol.2018.7852; HERMEKING H, 1994, SCIENCE, V265, P2091, DOI 10.1126/science.8091232; Hoffman B, 2008, ONCOGENE, V27, P6462, DOI 10.1038/onc.2008.312; Huber MA, 2005, CURR OPIN CELL BIOL, V17, P548, DOI 10.1016/j.ceb.2005.08.001; Islam MA, 2018, INT J MOL SCI, V19, DOI 10.3390/ijms19051405; Ji SH, 2018, EXP CELL RES, V370, P292, DOI 10.1016/j.yexcr.2018.06.031; Khalid E, 2016, TUMOR BIOL, V37, P14513, DOI 10.1007/s13277-016-5364-8; Khan N, 2007, CARCINOGENESIS, V28, P233, DOI 10.1093/carcin/bgl243; Kleiner DE, 1999, CANCER CHEMOTH PHARM, V43, pS42, DOI 10.1007/s002800051097; Kopustinskiene DM, 2020, NUTRIENTS, V12, DOI 10.3390/nu12020457; Kurokawa M, 2009, CELL, V138, P838, DOI 10.1016/j.cell.2009.08.021; Langers AMJ, 2008, BRIT J CANCER, V98, P1820, DOI 10.1038/sj.bjc.6604380; Lee HJ, 2018, NUTRIENTS, V10, DOI 10.3390/nu10081043; Li XY, 2013, J HEMATOL ONCOL, V6, DOI 10.1186/1756-8722-6-19; Li YY, 2018, ANTIOXIDANTS-BASEL, V7, DOI 10.3390/antiox7120187; Liao HB, 2012, PHARMACOGN MAG, V8, P156, DOI 10.4103/0973-1296.96570; Lin Y, 2014, PHARMACOGN MAG, V10, P278, DOI 10.4103/0973-1296.137368; Liu-Smith F, 2016, MOL NUTR FOOD RES, V60, P1264, DOI 10.1002/mnfr.201500822; Luo Y, 2018, OXID MED CELL LONGEV, V2018, DOI 10.1155/2018/8987173; Maclean KH, 2003, MOL CELL BIOL, V23, P7256, DOI 10.1128/MCB.23.20.7256-7270.2003; Maiuri MC, 2007, NAT REV MOL CELL BIO, V8, P741, DOI 10.1038/nrm2239; Malcomson F. 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DEC 1	2020	11	12					10448	10466		10.1039/d0fo02081h			19	Biochemistry & Molecular Biology; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Food Science & Technology	PG8DY	WOS:000599960700015	33241810				2022-04-25	
J	Chowchaikong, N; Nilwarangkoon, S; Laphookhieo, S; Tanunyutthawongse, C; Watanapokasin, R				Chowchaikong, Nittiya; Nilwarangkoon, Sirinun; Laphookhieo, Surat; Tanunyutthawongse, Chantra; Watanapokasin, Ramida			p38 inhibitor inhibits the apoptosis of cowanin-treated human colorectal adenocarcinoma cells	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						cowanin; colorectal cancer; apoptosis; mitogen-activated protein kinase; p38 inhibitor	ACTIVATED PROTEIN-KINASE; SIGNALING PATHWAYS; BCL-2 FAMILY; CANCER; DEATH; COLON; MITOCHONDRIAL; REGULATORS; XANTHONES; AUTOPHAGY	Colorectal cancer, which is the third most common type of cancer diagnosed in both men and women, is the leading cause of cancer-related deaths worldwide. Cowanin is a pure compound extracted from Garcinia cowa Roxb., a tree species present in Thailand, Malaysia and Myanmar. The crude extract has been demonstrated to have antitumor activity, inflammation induction, antibacterial activity, anti-inflammatory activity and antimalarial activity. In the present study, the effects of cowanin on apoptosis induction and on the apoptosis-related and mitogen-activated protein kinase (MAPK) pathways were investigated in the LoVo human colorectal cancer cell line. The cytotoxicity of cowanin in LoVo cells was determined by MTT assay. Hoechst 33342 and JC-1 staining were used to determine nuclear morphological changes and mitochondrial membrane potential, respectively. The expression levels of BCL2 apoptosis regulator (Bcl-2) family, MAPK and AKT serine/threonine kinase 1 (Akt) pathway proteins following cowanin treatment were determined by western blot analysis. The results demonstrated that cowanin inhibited cell proliferation and induced cell death via the apoptosis pathway. Cowanin treatment increased BCL2 associated X (Bax) and decreased Bcl-2 expression. In addition, cowanin activated caspase-9, -7 and poly-ADP-ribose-polymerase expression. Furthermore, cowanin decreased the levels of phosphorylated extracellular signal-regulated kinase (p-ERK), p-Akt, p-3-phosphoinositide-dependent protein kinase-1, while it increased p-p38 expression, thus resulting in the induction of apoptosis. In conclusion, cowanin inhibited cell proliferation and induced apoptosis of LoVo cells via the MAPK and Akt signaling pathways. Notably, inhibition of p38 by using a p38 inhibitor (SB203580) prevented the cowanin-induced apoptosis in LoVo cells. These results suggested that cowanin may be a potential candidate for the treatment of colorectal cancer and provided important information on the molecular mechanisms underlying its antitumor activity.	[Chowchaikong, Nittiya; Nilwarangkoon, Sirinun; Tanunyutthawongse, Chantra; Watanapokasin, Ramida] Srinakharinwirot Univ, Fac Med, Dept Biochem, 114 Sukhumvit 23, Bangkok 10110, Thailand; [Laphookhieo, Surat] Mae Fah Luang Univ, Fac Sci, Dept Chem, Muang 57100, Chiang Rai, Thailand		Watanapokasin, R (corresponding author), Srinakharinwirot Univ, Fac Med, Dept Biochem, 114 Sukhumvit 23, Bangkok 10110, Thailand.	ramidaw@g.swu.ac.th	laphookhieo, surat/AAA-9701-2019	laphookhieo, surat/0000-0002-4757-2781	Royal Golden Jubilee (RGJ) Ph.D. Program from the Thailand Research Fund (TRF) [PHD/0143/2553]	This study was supported by the Royal Golden Jubilee (RGJ) Ph.D. Program (grant no. PHD/0143/2553) from the Thailand Research Fund (TRF).	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J	Hai, Y; Shinsky, SA; Porter, NJ; Christianson, DW				Hai, Yang; Shinsky, Stephen A.; Porter, Nicholas J.; Christianson, David W.			Histone deacetylase 10 structure and molecular function as a polyamine deacetylase	NATURE COMMUNICATIONS			English	Article							INTERACTIVE TREE; ONLINE TOOL; LIFE ITOL; N-8-ACETYLSPERMIDINE; INHIBITION; SPERMIDINE; SUBSTRATE; AUTOPHAGY; DISPLAY; ELECTROSTATICS	Cationic polyamines such as spermidine and spermine are critical in all forms of life, as they regulate the function of biological macromolecules. Intracellular polyamine metabolism is regulated by reversible acetylation and dysregulated polyamine metabolism is associated with neoplastic diseases such as colon cancer, prostate cancer and neuroblastoma. Here we report that histone deacetylase 10 (HDAC10) is a robust polyamine deacetylase, using recombinant enzymes from Homo sapiens (human) and Danio rerio (zebrafish). The 2.85 angstrom-resolution crystal structure of zebrafish HDAC10 complexed with a transition-state analogue inhibitor reveals that a glutamate gatekeeper and a sterically constricted active site confer specificity for N-8-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. Both HDAC10 and spermidine are known to promote cellular survival through autophagy. Accordingly, this work sets a foundation for studying the chemical biology of autophagy through the structure-based design of inhibitors that may also serve as new leads for cancer chemotherapy.	[Hai, Yang; Shinsky, Stephen A.; Porter, Nicholas J.; Christianson, David W.] Univ Penn, Dept Chem, Roy & Diana Vagelos Labs, 231 South 34th St, Philadelphia, PA 19104 USA; [Hai, Yang] Univ Calif Los Angeles, Dept Chem & Biomol Engn, Los Angeles, CA 90095 USA		Christianson, DW (corresponding author), Univ Penn, Dept Chem, Roy & Diana Vagelos Labs, 231 South 34th St, Philadelphia, PA 19104 USA.	chris@sas.upenn.edu	Hai, Yang/N-6388-2015	Hai, Yang/0000-0002-2039-5367; Shinsky, Stephen/0000-0001-5437-1729; Porter, Nicholas/0000-0002-9803-5310	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [GM49758]; Department of Chemistry at the University of Pennsylvania; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM049758] Funding Source: NIH RePORTER	We thank C. Decroos and R. Marmorstein for helpful discussions, and we thank the NIH for grant GM49758 in support of this research. N.J.P. thanks the Department of Chemistry at the University of Pennsylvania for the award of a graduate research fellowship. In addition, we thank V. Stojanoff and S. Russi at BL 14-1 and T. Doukov at beamline 12-2 of the Stanford Synchrotron Radiation Lightsource for assistance with data collection.	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Commun.	MAY 18	2017	8								15368	10.1038/ncomms15368			9	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	EV1MG	WOS:000401509800001	28516954	Green Published, gold			2022-04-25	
J	Zhu, QW; Zhang, QC; Gu, M; Zhang, KW; Xia, T; Zhang, SY; Chen, WH; Yin, HM; Yao, H; Fan, Y; Pan, S; Xie, HJ; Liu, HT; Cheng, TY; Zhang, PP; Zhang, T; You, B; You, YW				Zhu, Qingwen; Zhang, Qicheng; Gu, Miao; Zhang, Kaiwen; Xia, Tian; Zhang, Siyu; Chen, Wenhui; Yin, Haimeng; Yao, Hui; Fan, Yue; Pan, Si; Xie, Haijing; Liu, Huiting; Cheng, Tianyi; Zhang, Panpan; Zhang, Ting; You, Bo; You, Yiwen			MIR106A-5pupregulation suppresses autophagy and accelerates malignant phenotype in nasopharyngeal carcinoma	AUTOPHAGY			English	Article						Autophagy; BTG3; malignant phenotype; MIR106A-5p; nasopharyngeal carcinoma	ENHANCES RADIOSENSITIVITY; PROMOTES PROLIFERATION; COLORECTAL-CANCER; GASTRIC-CANCER; CELLS; METASTASIS; EXPRESSION; INHIBITION; INVASION; GROWTH	Dysregulated microRNAs (miRNAs) are involved in carcinoma progression, metastasis, and poor prognosis. We demonstrated that in nasopharyngeal carcinoma (NPC), transactivatedMIR106A-5ppromotes a malignant phenotype by functioning as a macroautophagy/autophagy suppressor by targetingBTG3(BTG anti-proliferation factor 3) and activating autophagy-regulating MAPK signaling.MIR106A-5pexpression was markedly increased in NPC cases based on quantitative real-time PCR, miRNA microarray, and TCGA database analysis findings. Moreover,MIR106A-5pwas correlated with advanced stage, recurrence, and poor clinical outcomes in NPC patients. In addition to three-dimensional cell culture assays, zebrafish and BALB/c mouse tumor models revealed that overexpressedMIR106A-5ptargetedBTG3and accelerated the NPC malignant phenotype by inhibiting autophagy. BTG3 promoted autophagy, and its expression was correlated with poor prognosis in NPC. Attenuation of autophagy, mediated by theMIR106A-5p-BTG3 axis, occurred because of MAPK pathway activation.MIR106A-5poverexpression in NPC was due to increased transactivation by EGR1 and SOX9. Our findings may lead to novel insights into the pathogenesis of NPC.	[Zhu, Qingwen; Zhang, Qicheng; Gu, Miao; Zhang, Kaiwen; Xia, Tian; Zhang, Siyu; Chen, Wenhui; Yin, Haimeng; Yao, Hui; Fan, Yue; Pan, Si; Xie, Haijing; Liu, Huiting; Cheng, Tianyi; Zhang, Panpan; Zhang, Ting; You, Bo; You, Yiwen] Nantong Univ, Affiliated Hosp, Dept Otorhinolaryngol Head & Neck Surg, Nantong, Jiangsu, Peoples R China; [Zhu, Qingwen; Zhang, Qicheng; Gu, Miao; Zhang, Kaiwen; Xia, Tian; Zhang, Siyu; Chen, Wenhui; Yin, Haimeng; Yao, Hui; Fan, Yue; Pan, Si; Xie, Haijing; Liu, Huiting; Cheng, Tianyi; Zhang, Panpan; Zhang, Ting; You, Bo; You, Yiwen] Nantong Univ, Affiliated Hosp, Inst Otolaryngol Head & Neck Surg, Nantong, Jiangsu, Peoples R China		You, B; You, YW (corresponding author), Nantong Univ, Affiliated Hosp, Dept Otorhinolaryngol Head & Neck Surg, Nantong, Jiangsu, Peoples R China.	oubo19891014@163.com; youyiwen_nantong@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81972554, 81672682, 81602385]; Clinical Frontier Technology of Jiangsu [BE2017680]; CSCO Clinical Oncology Research Foundation of Beijing [Y-HS2017-074]; Clinical Medical Center of Nantong [HS2016001]; innovative research project for postgraduate students of Jiangsu province [SJCX19_0871, SJCX19_0872, SJCX18_0822]	This work was supported by grants from the National Natural Science Foundation of China (Grant No. 81972554, No. 81672682, No. 81602385), the Clinical Frontier Technology of Jiangsu (Grant No. BE2017680), the CSCO Clinical Oncology Research Foundation of Beijing (Grant No. Y-HS2017-074), the Clinical Medical Center of Nantong (Grant No. HS2016001), the innovative research project for postgraduate students of Jiangsu province (Grant No. SJCX19_0871, No. SJCX19_0872, No. SJCX18_0822).	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J	Momtazi-borojeni, AA; Abdollahi, E; Ghasemi, F; Caraglia, M; Sahebkar, A				Momtazi-borojeni, Amir A.; Abdollahi, Elham; Ghasemi, Faezeh; Caraglia, Michele; Sahebkar, Amirhossein			The novel role of pyrvinium in cancer therapy	JOURNAL OF CELLULAR PHYSIOLOGY			English	Review						cancer; cancer stem cell; pyrvinium	ANDROGEN RECEPTOR INHIBITION; BETA-CATENIN; STEM-CELLS; PROSTATE-CANCER; PHOSPHATIDYLINOSITOL 3-KINASE; AUTOPHAGY ADDICTION; ANTITUMOR-ACTIVITY; TUMOR-SUPPRESSOR; REPAIR PATHWAYS; GENE-EXPRESSION	Pyrvinium pamoate (PP) is a quinoline-derived cyanine dye which was officially approved by FDA for its anthelmintic properties and therapeutic function against animal-like protists such as Cryptosporidium parvum and Plasmodium falciparum in the 1950s. In the last 10 years, several studies have shown the novel activity of pyrvinium in tumor therapy. Some investigations have indicated that pyrvinium could delay or inhibit tumor cell proliferation in cancer models including colon, breast, lung and prostate cancer, and some hematological malignancies. In this review, we discuss multiple critical signaling pathways and mechanisms underlying the anticancer effects of PP. In details, pyrvinium acts through the following main mechanisms: (i) energy and autophagy depletion; and (ii) inhibition of Akt and Wnt--catenin-dependent pathways. Interestingly, pyrvinium has also shown potent anti-cancer stem cell activity. The overwhelming insights into the mechanism of anticancer properties of PP can help establishing novel and future anti-tumor treatment strategies.	[Momtazi-borojeni, Amir A.] Mashhad Univ Med Sci, Nanotechnol Res Ctr, Bu Ali Res Inst, Mashhad, Iran; [Momtazi-borojeni, Amir A.] Mashhad Univ Med Sci, Fac Med, Dept Med Biotechnol, Student Res Comm, Mashhad, Iran; [Abdollahi, Elham] Mashhad Univ Med Sci, Dept Med Immunol, Sch Med, Mashhad, Iran; [Abdollahi, Elham] Mashhad Univ Med Sci, Student Res Comm, Mashhad, Iran; [Ghasemi, Faezeh] Arak Univ Med Sci, Fac Med, Dept Med Biotechnol, Arak, Iran; [Caraglia, Michele] Univ Campania L Vanvitelli, Dept Biochem Biophys & Gen Pathol, Via L De Crecchio, Naples, Italy; [Sahebkar, Amirhossein] Mashhad Univ Med Sci, Biotechnol Res Ctr, Mashhad, Iran		Sahebkar, A (corresponding author), Mashhad Univ Med Sci, Sch Med, Dept Med Biotechnol, POB 91779-48564, Mashhad, Iran.	sahebkara@mums.ac.ir	Momtazi-Borojeni, Amir Abaas/AAC-6972-2019; Sahebkar, Amirhossein/B-5124-2018; Caraglia, Michele/AAK-4569-2020; Abdollahi, Elham/AAA-2731-2020	Momtazi-Borojeni, Amir Abaas/0000-0002-4376-1083; Caraglia, Michele/0000-0003-2408-6091; 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Cell. Physiol.	APR	2018	233	4					2871	2881		10.1002/jcp.26006			11	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	FR0AL	WOS:000418723200022	28500633				2022-04-25	
J	Tuorkey, MJ				Tuorkey, Muobarak J.			Cancer Therapy with Phytochemicals: Present and Future Perspectives	BIOMEDICAL AND ENVIRONMENTAL SCIENCES			English	Review							KINASE-C-DELTA; ROTTLERIN INDUCES AUTOPHAGY; APOPTOTIC CELL-DEATH; PANCREATIC-CANCER; PKC-DELTA; COLON-CANCER; IN-VITRO; SPARSTOLONIN B; UP-REGULATION; REDUCING MATRIX-METALLOPROTEINASE-9	Recently, a wide range of food-derived phytochemical compounds and their synthetic derivatives have been proposed for cancer treatment. Unfortunately, data available in related literature focus on the anti-cancer properties of compounds derived from edible plants, while very little is known about those derived from non-edible plants. And thus, the underlying mechanisms of their anti-cancer effects are yet to be elucidated. This review collates the available data on the anti-cancer activities of six phytochemical-derived compounds from edible and non-edible plants, i.e. rottlerin, berbamine, sparstolonin B, sulforaphane, plumbagin and 6-shogaol. These compounds are used as bioactive markers for cytotoxicity against tumors. As such, understanding their mode of action will provide the rationale for the combination strategies of these compounds with other drugs in the battle against cancer.	[Tuorkey, Muobarak J.] Damanhour Univ, Fac Sci, Div Physiol, Dept Zool, Damanhour 22111, Egypt		Tuorkey, MJ (corresponding author), Damanhour Univ, Fac Sci, Div Physiol, Dept Zool, Damanhour 22111, Egypt.	physio_mj_tuorkey@yahoo.com					Ashour AA, 2014, J CELL MOL MED, V18, P2235, DOI 10.1111/jcmm.12361; Ashour AA, 2014, APOPTOSIS, V19, P241, DOI 10.1007/s10495-013-0927-2; Baird L, 2014, BIOTECHNOL ADV; Balgi AD, 2009, PLOS ONE, V4, DOI 10.1371/journal.pone.0007124; Barile E, 2013, CHEM BIOL DRUG DES, V82, P520, DOI 10.1111/cbdd.12177; Bateman HR, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0070500; Bilandzic M, 2013, MOL ENDOCRINOL, V27, P466, DOI 10.1210/me.2012-1239; Bin Hafeez B, 2013, MOL ONCOL, V7, P428, DOI 10.1016/j.molonc.2012.12.001; Chang CC, 2013, J OVARIAN RES, V6, DOI 10.1186/1757-2215-6-41; Chen MB, 2013, CELL SIGNAL, V25, P1993, DOI 10.1016/j.cellsig.2013.05.026; Chen Zhao-fei, 2006, Zhonghua Zhongliu Zazhi, V28, P564; Cheng J, 2015, MOL ONCOL, V9, P105, DOI 10.1016/j.molonc.2014.07.024; 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Environ. Sci.	NOV	2015	28	11					808	819		10.1016/S0895-3988(15)30111-2			12	Environmental Sciences; Public, Environmental & Occupational Health	Science Citation Index Expanded (SCI-EXPANDED)	Environmental Sciences & Ecology; Public, Environmental & Occupational Health	DC3YW	WOS:000369157400004	26695359				2022-04-25	
S	Ashrafizadeh, M; Tavakol, S; Mohammadinejad, R; Ahmadi, Z; Yaribeygi, H; Jamialahmadi, T; Johnston, TP; Sahebkar, A		Barreto, GE; Sahebkar, A		Ashrafizadeh, Milad; Tavakol, Shima; Mohammadinejad, Reza; Ahmadi, Zahra; Yaribeygi, Habib; Jamialahmadi, Tannaz; Johnston, Thomas P.; Sahebkar, Amirhossein			Paving the Road Toward Exploiting the Therapeutic Effects of Ginsenosides: An Emphasis on Autophagy and Endoplasmic Reticulum Stress	PHARMACOLOGICAL PROPERTIES OF PLANT-DERIVED NATURAL PRODUCTS AND IMPLICATIONS FOR HUMAN HEALTH	Advances in Experimental Medicine and Biology		English	Article; Book Chapter						Ginsenoside; Endoplasmic reticulum stress; Autophagy; Apoptosis; Cancer therapy	TUMOR-NECROSIS-FACTOR; RG1 PROTECTS CARDIOMYOCYTES; COLON-CANCER CELLS; ER STRESS; INDUCED APOPTOSIS; OXIDATIVE STRESS; PC12 CELLS; IN-VITRO; HYPOXIA/REOXYGENATION INJURY; DIABETIC CARDIOMYOPATHY	Programmed cell death processes such as apoptosis and autophagy strongly contribute to the onset and progression of cancer. Along with these lines, modulation of cell death mechanisms to combat cancer cells and elimination of resistance to apoptosis is of great interest. It appears that modulation of autophagy and endoplasmic reticulum (ER) stress with specific agents would be beneficial in the treatment of several disorders. Interestingly, it has been suggested that herbal natural products may be suitable candidates for the modulation of these processes due to few side effects and significant therapeutic potential. Ginsenosides are derivatives of ginseng and exert modulatory effects on the molecular mechanisms associated with autophagy and ER stress. Ginsenosides act as smart phytochemicals that confer their effects by up-regulating ATG proteins and converting LC3-I to -II, which results in maturation of autophagosomes. Not only do ginsenosides promote autophagy but they also possess protective and therapeutic properties due to their capacity to modulate ER stress and up- and down-regulate and/or dephosphorylate UPR transducers such as IRE1, PERK, and ATF6. Thus, it would appear that ginsenosides are promising agents to potentially restore tissue malfunction and possibly eliminate cancer.	[Ashrafizadeh, Milad] Sabanci Univ, Fac Engn & Nat Sci, Istanbul, Turkey; [Ashrafizadeh, Milad] Sabanci Univ Nanotechnol Res & Applicat Ctr SUNUM, Istanbul, Turkey; [Tavakol, Shima] Iran Univ Med Sci, Cellular & Mol Res Ctr, Tehran, Iran; [Mohammadinejad, Reza] Kerman Univ Med Sci, Inst Neuropharmacol, Neurosci Res Ctr, Kerman, Iran; [Ahmadi, Zahra] Islamic Azad Univ, Dept Basic Sci, Shoushtar Branch, Shoushtar, Iran; [Yaribeygi, Habib] Semnan Univ Med Sci, Physiol Res Ctr, Semnan, Iran; [Jamialahmadi, Tannaz] Islamic Azad Univ, Dept Food Sci & Technol, Quchan Branch, Quchan, Iran; [Jamialahmadi, Tannaz] Mashhad Univ Med Sci, Fac Med, Dept Nutr, Mashhad, Razavi Khorasan, Iran; [Johnston, Thomas P.] Univ Missouri Kansas City, Sch Pharm, Div Pharmacol & Pharmaceut Sci, Kansas City, MO USA; [Sahebkar, Amirhossein] Mashhad Univ Med Sci, Appl Biomed Res Ctr, Mashhad, Razavi Khorasan, Iran; [Sahebkar, Amirhossein] Mashhad Univ Med Sci, Pharmaceut Technol Inst, Biotechnol Res Ctr, Mashhad, Razavi Khorasan, Iran; [Sahebkar, Amirhossein] Mashhad Univ Med Sci, Sch Pharm, Mashhad, Razavi Khorasan, Iran; [Sahebkar, Amirhossein] Polish Mothers Mem Hosp Res Inst PMMHRI, Lodz, Poland		Yaribeygi, H (corresponding author), Semnan Univ Med Sci, Physiol Res Ctr, Semnan, Iran.; Sahebkar, A (corresponding author), Mashhad Univ Med Sci, Appl Biomed Res Ctr, Mashhad, Razavi Khorasan, Iran.; Sahebkar, A (corresponding author), Mashhad Univ Med Sci, Pharmaceut Technol Inst, Biotechnol Res Ctr, Mashhad, Razavi Khorasan, Iran.; Sahebkar, A (corresponding author), Mashhad Univ Med Sci, Sch Pharm, Mashhad, Razavi Khorasan, Iran.; Sahebkar, A (corresponding author), Polish Mothers Mem Hosp Res Inst PMMHRI, Lodz, Poland.	habib.yari@yahoo.com; sahebkara@mums.ac.ir	Yaribeygi, Habib/R-8998-2019	Yaribeygi, Habib/0000-0002-1706-6212; Jami, Tannaz/0000-0001-9521-3153			Ahmadi Z, 2020, FUND CLIN PHARMACOL, V34, P11, DOI 10.1111/fcp.12498; Ahmadi Z, 2019, J DRUG DELIV SCI TEC, V51, P591, DOI 10.1016/j.jddst.2019.03.017; Ahuja A, 2018, J GINSENG RES, V42, P248, DOI 10.1016/j.jgr.2017.04.009; 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978-3-030-64871-8	ADV EXP MED BIOL	Adv.Exp.Med.Biol.		2021	1308						137	160		10.1007/978-3-030-64872-5_12	10.1007/978-3-030-64872-5		24	Chemistry, Medicinal; Medicine, Research & Experimental; Pharmacology & Pharmacy	Book Citation Index – Science (BKCI-S); Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy; Research & Experimental Medicine	BR3MG	WOS:000647701200012	33861443				2022-04-25	
J	Khaket, TP; Singh, MP; Khan, I; Kang, SC				Khaket, Tejinder Pal; Singh, Mahendra Pal; Khan, Imran; Kang, Sun Chul			In vitro and in vivo studies on potentiation of curcumin-induced lysosomal-dependent apoptosis upon silencing of cathepsin C in colorectal cancer cells	PHARMACOLOGICAL RESEARCH			English	Article						Cathepsins; Autophagy; Endoplasmic reticulum stress; Apoptosis	AUTOPHAGY INDUCTION; PROTEIN-SYNTHESIS; DEATH; INHIBITION; INVASION; GROWTH; JNK; PERMEABILIZATION; REGULATOR; MIGRATION	Cathepsins are lysosomal acid hydrolases that make crucial contributions to tumor progression through a variety of signaling mechanisms, including autophagy, cell survival, chemotherapeutic resistance, and metastasis. Herein, we report that cathepsin C (CTSC) silencing upregulates the anticancer potential of curcumin in colorectal cancer cells (CRCs) both in vitro and in athymic mice xenografts. Curcumin treatment enhances CTSC level in CRCs; however, CTSC silencing with subsequent curcumin treatment (sequential treatment) induces ER stress and autophagic dysregulation accompanied by lysosomal permeabilization and ROS generation. This lysosomal permeabilization triggered the cytosolic CTSB mediated BID-dependent mitochondrial membrane permeabilization and thereby caspase-dependent apoptosis. This phenotype can be rescued by CTSB inhibition and NAC, which further supported the involvement of ROS and CTSB in apoptosis following sequential treatment. Indeed, the sequential CTSC silencing and curcumin treatment also significantly curtailed tumor volume as well as ameliorated cytosolic cyt c and tBID protein levels in tumor tissues compared to those in control and individual treatments of CTSC targeting and on curcumin treatment in nude mice xenografts. The results reveal that CTSC can controls the curcumin-induced cytotoxic insult through autophagy maintenance both in vitro and in athymic mice xenografts, thereby providing an insight into the role of CTSC in chemoprevention of CRCs.	[Khaket, Tejinder Pal; Singh, Mahendra Pal; Khan, Imran; Kang, Sun Chul] Daegu Univ, Dept Biotechnol, Gyongsan 38453, Gyeongbuk, South Korea; [Khaket, Tejinder Pal] Ohio State Univ, Comprehens Canc Ctr, Dept Radiat Oncol, Columbus, OH 43210 USA; [Singh, Mahendra Pal] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA; [Khan, Imran] Univ Minnesota, Hormel Inst, 801 16th Ave NE, Austin, MN 55912 USA		Kang, SC (corresponding author), Daegu Univ, Coll Engn, Dept Biotechnol, Gyongsan 38453, Gyeongbuk, South Korea.	sckang@daegu.ac.kr	Singh, Mahendra Pal/J-8391-2019		National Research Foundation of Korea (NRF)National Research Foundation of Korea [NRF 2019R1A2B5B01070543]	This work was supported by the National Research Foundation of Korea (NRF) NRF 2019R1A2B5B01070543.	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Res.	NOV	2020	161								105156	10.1016/j.phrs.2020.105156			15	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	PI3JG	WOS:000600990100043	32835867				2022-04-25	
J	Woo, Y; Lee, HJ; Jung, YM; Jung, YJ				Woo, Yunseo; Lee, Hyo-Ji; Jung, Young Mee; Jung, Yu-Jin			Regulated Necrotic Cell Death in Alternative Tumor Therapeutic Strategies	CELLS			English	Review						apoptosis; autophagy; necrosis; necroptosis; pyroptosis; ferroptosis; therapy-resistant tumors	DOMAIN-LIKE PROTEIN; COLON-CANCER CELLS; INFLAMMASOME ACTIVATION; DEPENDENT NECROPTOSIS; MOLECULAR-MECHANISMS; AUTOPHAGY INHIBITION; PROGRAMMED NECROSIS; NLRP3 INFLAMMASOME; OXIDATIVE STRESS; POOR-PROGNOSIS	The treatment of tumors requires the induction of cell death. Radiotherapy, chemotherapy, and immunotherapy are administered to kill cancer cells; however, some cancer cells are resistant to these therapies. Therefore, effective treatments require various strategies for the induction of cell death. Regulated cell death (RCD) is systematically controlled by intracellular signaling proteins. Apoptosis and autophagy are types of RCD that are morphologically different from necrosis, while necroptosis, pyroptosis, and ferroptosis are morphologically similar to necrosis. Unlike necrosis, regulated necrotic cell death (RNCD) is caused by disruption of the plasma membrane under the control of specific proteins and induces tissue inflammation. Various types of RNCD, such as necroptosis, pyroptosis, and ferroptosis, have been used as therapeutic strategies against various tumor types. In this review, the mechanisms of necroptosis, pyroptosis, and ferroptosis are described in detail, and a potential effective treatment strategy to increase the anticancer effects on apoptosis- or autophagy-resistant tumor types through the induction of RNCD is suggested.	[Woo, Yunseo; Lee, Hyo-Ji; Jung, Yu-Jin] Kangwon Natl Univ, Dept Biol Sci, Chunchon 24341, South Korea; [Woo, Yunseo; Lee, Hyo-Ji; Jung, Young Mee; Jung, Yu-Jin] Kangwon Natl Univ, Kangwon Radiat Convergence Res Support Ctr, Chunchon 24341, South Korea; [Jung, Young Mee] Kangwon Natl Univ, Dept Chem, Chunchon 24341, South Korea; [Jung, Yu-Jin] Kangwon Natl Univ, BIT Med Convergence Grad Program, Chunchon 24341, South Korea		Jung, YJ (corresponding author), Kangwon Natl Univ, Dept Biol Sci, Chunchon 24341, South Korea.; Jung, YJ (corresponding author), Kangwon Natl Univ, Kangwon Radiat Convergence Res Support Ctr, Chunchon 24341, South Korea.; Jung, YJ (corresponding author), Kangwon Natl Univ, BIT Med Convergence Grad Program, Chunchon 24341, South Korea.	yunseo@kangwon.ac.kr; koko7912@kangwon.ac.kr; ymjung@kangwon.ac.kr; yjjung@kangwon.ac.kr		Jung, Young Mee/0000-0003-4362-0990; Lee, Hyo-Ji/0000-0001-9892-8365; Jung, Yu-Jin/0000-0002-4942-677X	Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science, and Technology [2018R1D1A1B07049097]; Korea Basic Science Institute (National Research Facilities and Equipment Center) - Ministry of Education [2020R1A6C101A195]	This research was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education, Science, and Technology (2018R1D1A1B07049097), and by a Korea Basic Science Institute (National Research Facilities and Equipment Center) grant funded by the Ministry of Education (2020R1A6C101A195).	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J	Prabhu, V; Srivastava, P; Yadav, N; Amadori, M; Schneider, A; Seshadri, A; Pitarresi, J; Scott, R; Zhang, HH; Koochekpour, S; Gogada, R; Chandra, D				Prabhu, Varun; Srivastava, Pragya; Yadav, Neelu; Amadori, Michael; Schneider, Andrea; Seshadri, Athul; Pitarresi, Jason; Scott, Rachael; Zhang, Honghao; Koochekpour, Shahriar; Gogada, Raghu; Chandra, Dhyan			Resveratrol depletes mitochondrial DNA and inhibition of autophagy enhances resveratrol-induced caspase activation	MITOCHONDRION			English	Article						Resveratrol; Mitochondria; Autophagy; Apoptosis; Mitochondrial DNA	BREAST-CANCER CELLS; CHRONIC MYELOGENOUS LEUKEMIA; ISOLATED RAT HEPATOCYTES; INDUCED APOPTOSIS; AMPK ACTIVATION; IN-VIVO; DEATH; MECHANISMS; BAX; CHEMOPREVENTION	We recently demonstrated that resveratrol induces caspase-dependent apoptosis in multiple cancer cell types. Whether apoptosis is also regulated by other cell death mechanisms such as autophagy is not clearly defined. Here we show that inhibition of autophagy enhanced resveratrol-induced caspase activation and apoptosis. Resveratrol inhibited colony formation and cell proliferation in multiple cancer cell types. Resveratrol treatment induced accumulation of LC3-II, which is a key marker for autophagy. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, increased resveratrol-mediated caspase activation and cell death in breast and colon cancer cells. Inhibition of autophagy by silencing key autophagy regulators such as ATG5 and Beclin-1 enhanced resveratrol-induced caspase activation. Mechanistic analysis revealed that Beclin-1 did not interact with proapoptotic proteins Bax and Bak; however, Beclin-1 was found to interact with p53 in the cytosol and mitochondria upon resveratrol treatment. Importantly, resveratrol depleted ATPase 8 gene, and thus, reduced mitochondrial DNA (mtDNA) content, suggesting that resveratrol induces damage to mtDNA causing accumulation of dysfunctional mitochondria triggering autophagy induction. Together, our findings indicate that induction of autophagy during resveratrol-induced apoptosis is an adaptive response. (C) 2012 Elsevier B.V. and Mitochondria Research Society. All rights reserved.	[Prabhu, Varun; Srivastava, Pragya; Yadav, Neelu; Amadori, Michael; Schneider, Andrea; Seshadri, Athul; Pitarresi, Jason; Scott, Rachael; Zhang, Honghao; Koochekpour, Shahriar; Gogada, Raghu; Chandra, Dhyan] Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA		Chandra, D (corresponding author), Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Elm & Carlton St, Buffalo, NY 14263 USA.	dhyan.chandra@roswellpark.org	Gogada, Raghu/AAG-6624-2019	Gogada, Raghu/0000-0003-0933-7999; Chandra, Dhyan/0000-0001-7272-9384; Zhang, Honghao/0000-0002-2338-6992	National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [CA123142]; National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA016056]; American Cancer SocietyAmerican Cancer Society [RSG-12-214-01 - CCG]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [K01CA123142, P30CA016056] Funding Source: NIH RePORTER	This work was supported by National Institutes of Health K01 award CA123142 to Dhyan Chandra and National Cancer Institute Center Support Grant CA016056 to Roswell Park Cancer Institute. Dhyan Chandra was supported by a Research Scholar Grant, RSG-12-214-01 - CCG from the American Cancer Society. We thank Dr. Bert Vogelstein for providing HCT116 cells. Varun Prabhu was an MS student at University at Buffalo. We apologize to all colleagues whose work could not be cited due to space constraints.	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J	Ferreira, PMP; de Sousa, RWR; Ferreira, JRD; Militao, GCG; Bezerra, DP				Pinheiro Ferreira, Paulo Michel; Ramos de Sousa, Rayran Walter; de Oliveira Ferreira, Jose Roberto; Gadelha Militao, Gardenia Carmen; Bezerra, Daniel Pereira			Chloroquine and hydroxychloroquine in antitumor therapies based on autophagy-related mechanisms	PHARMACOLOGICAL RESEARCH			English	Review						Cell death; Chemoresistance; Immunomodulatory properties; Clinical option	MIXED LINEAGE KINASE; COLON-CANCER CELLS; CPG-DNA; INHIBITION; RESISTANCE; P53; DEATH; RIP3; DRUG; CYTOTOXICITY	Chloroquine (CQ) and hydroxychloroquine (HCQ) are the most common drugs used to relieve acute and chronic inflammatory diseases. In this article, we present a review about the use of CQ and HCQ in antitumor therapies based on autophagy mechanisms. These molecules break/discontinue autophagosome-lysosome fusions in initial phases and enhance antiproliferative action of chemotherapeutics. Their sensitizing effects of chemotherapy when used as an adjuvant option in clinical trials against cancer. However, human related-MDR genes are also under risk to develop chemo or radioresistance because cancer cells have ability to throw 4-aminoquinolines out from digestive vacuoles well. Additionally, they also have antitumor mechanism unrelated to autophagy, including cell death from apoptosis and necroptosis and immunomodulatory/anti-inflammatory properties. However, the link between some anticancer mechanisms, clinical efficacy and pharmacological safety has not yet been fully defined.	[Pinheiro Ferreira, Paulo Michel; Ramos de Sousa, Rayran Walter] Univ Fed Piaui, Dept Biophys & Physiol, Lab Expt Cancerol, BR-64049550 Teresina, Brazil; [de Oliveira Ferreira, Jose Roberto] State Univ Hlth Sci Alagoas, Ctr Integrat Sci, BR-57010382 Maceio, Alagoas, Brazil; [Gadelha Militao, Gardenia Carmen] Univ Fed Pernambuco, Dept Physiol & Pharmacol, BR-50670901 Recife, PE, Brazil; [Bezerra, Daniel Pereira] Oswaldo Cruz Fdn IGM FIOCRUZ BA, Goncalo Moniz Inst, BR-40296710 Salvador, BA, Brazil		Ferreira, PMP (corresponding author), Univ Fed Piaui, Dept Biophys & Physiol, Lab Expt Cancerol LabCanc, Ctr Hlth Sci, Univ Ave, BR-64049550 Teresina, Piaui, Brazil.	pmpf@ufpi.edu.br	Ferreira, Paulo Michel Pinheiro/J-6783-2012	Ferreira, Paulo Michel Pinheiro/0000-0001-6862-6497	Brazilian agency "Conselho Nacional de Desenvolvimento Cientifico e Tecnologico" (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [303247/2019-3, 313350/2018-3]	Dr Paulo Michel Pinheiro Ferreira and Dr Daniel Pereira Bezerra are grateful to the Brazilian agency "Conselho Nacional de Desenvolvimento Cientifico e Tecnologico" (CNPq) for their personal scholarships (#303247/2019-3 and #313350/2018-3, respectively).	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Res.	MAR	2021	168								105582	10.1016/j.phrs.2021.105582		APR 2021	9	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	SJ4FE	WOS:000655486900007	33775862				2022-04-25	
J	Vecera, L; Gabrhelik, T; Prasil, P; Stourac, P				Vecera, L.; Gabrhelik, T.; Prasil, P.; Stourac, P.			The role of cannabinoids in the treatment of cancer	BRATISLAVA MEDICAL JOURNAL-BRATISLAVSKE LEKARSKE LISTY			English	Review						cannabinoids; cannabinoid receptor; cancer; oncological diseases; cancer treatment	EPITHELIAL-MESENCHYMAL TRANSITION; PROTEIN-COUPLED RECEPTOR; CELL LUNG-CANCER; TUMOR-GROWTH; IN-VIVO; INDUCED APOPTOSIS; CB2 RECEPTOR; COLON-CANCER; CHOLANGIOCARCINOMA GROWTH; INHIBITS ANGIOGENESIS	AIM: The aim of this review article is to summarize current knowledge about the role of cannabinoids and cannabinoid receptors in tumor disease modulation and to evaluate comprehensively the use of cannabinoids in cancer patients. METHOD: According to the PRISMA protocol, we have included data from a total of 105 articles. RESULTS: Cannabinoids affect cancer progression by three mechanisms. The most important mechanism is the stimulation of autophagy and affecting the signaling pathways leading to apoptosis. The most important mechanism of this process is the accumulation of ceramide. Cannabinoids also stimulate apoptosis by mechanisms independent of autophagy. Other mechanisms by which cannabinoids affect tumor growth are inhibition of tumor angiogenesis, invasiveness, metastasis, and the modulation of the anti-tumor immune response. CONCLUSION: In addition to the symptomatic therapy of cancer patients, the antitumor effects of cannabinoids (whether in monotherapy or in combination with other cancer therapies) have promising potential in the treatment of cancer patients. More clinical trials are needed to demonstrate the antitumor effect of cannabinoids (Tab. 1, Fig. 1, Ref. 167).	[Vecera, L.; Gabrhelik, T.; Prasil, P.; Stourac, P.] Tomas Bata Hosp Zlin, Dept Emergency Med, Zlin, Czech Republic; [Vecera, L.; Stourac, P.] Masaryk Univ, Univ Hosp Brno, Med Fac, Dept Paediat Anaesthesiol & Intens Care Med, Brno, Czech Republic; [Gabrhelik, T.] Tomas Bata Hosp Zlin, Dept Anaesthesiol Resuscitat & Intens Care Med, Havlickovo Nabrezi 600, Zlin 76275, Czech Republic; [Prasil, P.] Dist Hosp Amstetten, Dept Anaesthesia & Intens Care Med, Amstetten, Austria		Gabrhelik, T (corresponding author), Tomas Bata Hosp Zlin, Dept Anaesthesiol Resuscitat & Intens Care Med, Havlickovo Nabrezi 600, Zlin 76275, Czech Republic.	Tomas.Gabrhelik@bnzlin.cz	Stourac, Petr/J-3610-2012	Stourac, Petr/0000-0003-1944-5926	 [NV18-03-00470]	This work was supported by grant no: NV18-03-00470.	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J	Hidayat, AFA; Chan, CK; Mohamad, J; Kadir, HA				Hidayat, Ahmad Fadhlurrahman Ahmad; Chan, Chim Kei; Mohamad, Jamaludin; Kadir, Habsah Abdul			Dioscorea bulbifera induced apoptosis through inhibition of ERK 1/2 and activation of JNK signaling pathways in HCT116 human colorectal carcinoma cells	BIOMEDICINE & PHARMACOTHERAPY			English	Article						Apoptosis; Colon cancer; Dioscorea bulbifera; ERK1/2 and JNK	REGULATED KINASE-1/2; REACTIVE OXYGEN; CANCER-CELLS; MAPK; PHOSPHORYLATION; INDUCTION; AUTOPHAGY; CASPASES; TUBERS; L.	Dioscorea bulbifera, also known as air potato, has been cultivated as food crop mainly in tropical countries in Asia and Australia. The tubers are edible and have often been used in Traditional Chinese Medicine (TCM) and Ayurvedic medicine to treat cancer, diabetes, thyroid disease, and inflammation. This study aimed to investigate the effects of D. bulbifera on HCT116 human colorectal carcinoma cells and to unravel the plausible mechanisms underlying its apoptotic effects. The ethanol crude and fractions (hexane, ethyl acetate and water) of D. bulbifera were subjected to cell viability MTT assay against various cancer cell lines. The lowest IC50 of the extract and fractions on selected cancer cells were selected for further apoptosis assay and western blot analysis. HCT116 cancer cells were treated with D. bulbifera and stained with Annexin/PI or Hoechst 33342/PI for preliminary confirmation of apoptosis. The dissipation of mitochondria membrane potential (MMP) was determined by flow cytometry. The protein expressions of apoptosis-related proteins such as Bcl-2 family, caspases, Fas, PARP, ERK1/2 and JNK were detected by western blot analysis. Moreover, the HCT116 cells were treated with UO126 and SP600125 inhibitors to verify the involvement of ERK1/2 and JNK protein expressions in inducing apoptotic cell death. Based on the result, D. bulbifera ethyl acetate fraction (DBEAF) exhibited the most compelling cytotoxicity on HCT116 cells with an IC50 of 37.91 +/- 1.30 mu g/mL. The induction of apoptosis was confirmed by phosphatidylserine externalization and chromatin condensation. Depolarization of MMP further conferred the induction of apoptosis was through the regulation of Bcl-2 family proteins. Activation of caspase cascades (caspase-3, -9, -8 and -10) was elicited followed by the observation of cleaved PARP accumulation in DBEAFtreated cells. Furthermore, death receptor, Fas was activated upon exposure to DBEAF. Collective apoptotic evidences suggested the involvement of intrinsic and extrinsic pathways by DBEAF in HCT116 cells. Interestingly, the attenuation of ERK1/2 phosphorylation accompanied by the activation of JNK was detected in DBEAF-treated cells. In conclusion, the findings revealed that DBEAF induced apoptosis through intrinsic and extrinsic pathways involving ERK1/2 and JNK.	[Hidayat, Ahmad Fadhlurrahman Ahmad; Chan, Chim Kei; Kadir, Habsah Abdul] Univ Malaya, Fac Sci, Inst Biol Sci, Biomol Res Grp,Biochem Program, Kuala Lumpur 50603, Malaysia; [Mohamad, Jamaludin] Univ Malaya, Fac Sci, Inst Biol Sci, Biohlth Program, Kuala Lumpur 50603, Malaysia		Kadir, HA (corresponding author), Univ Malaya, Fac Sci, Inst Biol Sci, Biomol Res Grp,Biochem Program, Kuala Lumpur 50603, Malaysia.	habsah@um.edu.my	MOHAMAD, J/B-8690-2010	Chan, Chim kei/0000-0002-1606-8814	Fundamental Research Grant Scheme (FRGS) from the Ministry of Education, Malaysia [FP009-2014B]	This study was supported by the Fundamental Research Grant Scheme (FRGS) FP009-2014B from the Ministry of Education, Malaysia.	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Pharmacother.	AUG	2018	104						806	816		10.1016/j.biopha.2018.05.073			11	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	GL1BQ	WOS:000436830700092	29860114				2022-04-25	
J	Garufi, A; Ricci, A; Trisciuoglio, D; Iorio, E; Carpinelli, G; Pistritto, G; Cirone, M; D'Orazi, G				Garufi, A.; Ricci, A.; Trisciuoglio, D.; Iorio, E.; Carpinelli, G.; Pistritto, G.; Cirone, M.; D'Orazi, G.			Glucose restriction induces cell death in parental but not in homeodomain-interacting protein kinase 2-depleted RKO colon cancer cells: molecular mechanisms and implications for tumor therapy	CELL DEATH & DISEASE			English	Article						HIPK2; glucose; tumor; cell death; autophagy; zinc supplementation	P53 ACTIVITY; HIPK2; HYPOXIA; ACTIVATION; APOPTOSIS; AUTOPHAGY; TRANSCRIPTION; TOLERANCE; GENE; DEPRIVATION	Tumor cell tolerance to nutrient deprivation can be an important factor for tumor progression, and may depend on deregulation of both oncogenes and oncosuppressor proteins. Homeodomain-interacting protein kinase 2 (HIPK2) is an oncosuppressor that, following its activation by several cellular stress, induces cancer cell death via p53-dependent or -independent pathways. Here, we used genetically matched human RKO colon cancer cells harboring wt-HIPK2 (HIPK2(+/+)) or stable HIPK2 siRNA interference (siHIPK2) to investigate in vitro whether HIPK2 influenced cell death in glucose restriction. We found that glucose starvation induced cell death, mainly due to c-Jun NH2-terminal kinase activation, in HIPK2(+/+)cells compared with siHIPK2 cells that did not die. 1 H-nuclear magnetic resonance quantitative metabolic analyses showed a marked glycolytic activation in siHIPK2 cells. However, treatment with glycolysis inhibitor 2-deoxy-D-glucose induced cell death only in HIPK2(+/+) cells but not in siHIPK2 cells. Similarly, siGlut-1 interference did not re-establish siHIPK2 cell death under glucose restriction, whereas marked cell death was reached only after zinc supplementation, a condition known to reactivate misfolded p53 and inhibit the pseudohypoxic phenotype in this setting. Further siHIPK2 cell death was reached with zinc in combination with autophagy inhibitor. We propose that the metabolic changes acquired by cells after HIPK2 silencing may contribute to induce resistance to cell death in glucose restriction condition, and therefore be directly relevant for tumor progression. Moreover, elimination of such a tolerance might serve as a new strategy for cancer therapy.	[Garufi, A.; D'Orazi, G.] Regina Elena Inst Canc Res, Dept Expt Oncol, Mol Oncogenesis Lab, Rome, Italy; [Ricci, A.; Iorio, E.; Carpinelli, G.] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy; [Trisciuoglio, D.] Regina Elena Inst Canc Res, Expt Chemotherapy Lab, Rome, Italy; [Pistritto, G.] Univ Roma Tor Vergata, Dept Neurosci, Pharmacol Sect, Rome, Italy; [Cirone, M.] Sapienza Univ, Ist Pasteur Fdn Cenci Bolognetti, Dept Expt Med, Rome, Italy; [D'Orazi, G.] Univ G DAnnunzio, Dept Med Oral & Biotechnol Sci, I-66013 Chieti, Italy		D'Orazi, G (corresponding author), Univ G DAnnunzio, Dept Med Oral & Biotechnol Sci, Via Vestini 31, I-66013 Chieti, Italy.	gdorazi@unich.it	Iorio, Egidio/M-7077-2017; D'Orazi, Gabriella/T-2792-2019; Garufi, Alessia/AAT-3363-2020; trisciuoglio, daniela/AAL-4002-2021; trisciuoglio, Daniela/H-2131-2016	Iorio, Egidio/0000-0001-6673-3838; D'Orazi, Gabriella/0000-0001-6876-9105; trisciuoglio, Daniela/0000-0002-7007-7914; Garufi, Alessia/0000-0001-9354-993X	Associazione Italiana per la Ricerca sul Cancro (AIRC)Fondazione AIRC per la ricerca sul cancro [IG 11377]; My First AIRC grantFondazione AIRC per la ricerca sul cancro [MFAG 11502]	This study was supported by grant form Associazione Italiana per la Ricerca sul Cancro (AIRC, IG 11377, to GD) and My First AIRC grant (MFAG 11502, to DT). We are greatly indebted to Drs. L Di Renzo and G Bossi for their helpful advice, stimulating discussion and for sharing reagents. GD dedicates this study to the memory of Professor David Givol who with a combination of intelligence, passion, vision, and organization was a precious and challenging collaborator and an unforgettable friend. We also dedicate this study to the memory of Professor Rita Levi Montalcini. May her outstanding contribution to science be an immortal legacy and an example for us all.	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MAY	2013	4								e639	10.1038/cddis.2013.163			11	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	156LR	WOS:000319824100028	23703384	Green Published, gold			2022-04-25	
J	Zhao, YL; Zhou, Y; Wang, MF				Zhao, Yueliang; Zhou, Yue; Wang, Mingfu			Brosimone I, an isoprenoid-substituted flavonoid, induces cell cycle G(1) phase arrest and apoptosis through ROS-dependent endoplasmic reticulum stress in HCT116 human colon cancer cells	FOOD & FUNCTION			English	Article							ER STRESS; AMPK; AUTOPHAGY; GROWTH; DEATH; CALCIUM; HOMEOSTASIS; INHIBITION; QUERCETIN; ACTIVATOR	Brosimone I is an isoprenoid-substituted flavonoid from Artocarpus heterophyllus. Here, we reported for the first time that brosimone I induced cell cycle G(1) phase arrest and apoptosis in HCT116 human colon cancer cells. Brosimone I treatment increased the cytosolic Ca2+ level, and subsequently activated the CaMKK-AMPK pathway. STO-609, a CaMKK inhibitor, and compound C, an AMPK-specific inhibitor, attenuated brosimone I-induced loss of cell viability in HCT116 cells. Furthermore, brosimone I enhanced ER stress. Salubrinal, an ER stress inhibitor, reduced brosimone I-induced cell growth inhibition. In addition, brosimone I was found to increase ROS generation and the inhibition of ROS formation by NAC, a ROS inhibitor, attenuated brosimone I-induced cell death, cytosolic Ca2+ increase, and ER stress markers. Collectively, our findings reveal that brosimone I induces cell cycle G(1) phase arrest and apoptosis via the induction of ROS-mediated increased cytosolic Ca2+, ER stress, and the activation of the CaMKK-AMPK signaling pathway.	[Zhao, Yueliang; Wang, Mingfu] Shanghai Ocean Univ, Coll Food Sci & Technol, Shanghai 201306, Peoples R China; [Zhao, Yueliang] Minist Agr, Lab Qual & Safety Risk Assessment Aquat Prod Stor, Shanghai 201306, Peoples R China; [Zhao, Yueliang; Zhou, Yue; Wang, Mingfu] Univ Hong Kong, Sch Biol Sci, Pokfulam Rd, Hong Kong, Peoples R China		Wang, MF (corresponding author), Shanghai Ocean Univ, Coll Food Sci & Technol, Shanghai 201306, Peoples R China.; Wang, MF (corresponding author), Univ Hong Kong, Sch Biol Sci, Pokfulam Rd, Hong Kong, Peoples R China.	mfwang@hku.hk	Wang, Mingfu/D-3136-2009; Wang, Mingfu/AAT-3292-2021	Wang, Mingfu/0000-0003-1469-3963; 	Hong Kong Research Grants Council (GRF Project)Hong Kong Research Grants Council [17154816]	The research was supported by the Hong Kong Research Grants Council (GRF Project No.: 17154816). The authors would like to thank Ms Iris M. Y. Tse for her technical support and kind advice on this research.	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MAY 1	2019	10	5					2729	2738		10.1039/c8fo02315h			10	Biochemistry & Molecular Biology; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Food Science & Technology	HZ8ZR	WOS:000469145900038	31038133				2022-04-25	
J	Han, WD; Sun, J; Feng, LF; Wang, KF; Li, D; Pan, Q; Chen, Y; Jin, W; Wang, X; Pan, HM; Jin, HC				Han, Weidong; Sun, Jie; Feng, Lifeng; Wang, KaiFeng; Li, Da; Pan, Qin; Chen, Yan; Jin, Wei; Wang, Xian; Pan, Hongming; Jin, Hongchuan			Autophagy Inhibition Enhances Daunorubicin-Induced Apoptosis in K562 Cells	PLOS ONE			English	Article							COLON-CANCER CELLS; SIGNALING PATHWAYS; DRUG-RESISTANCE; JNK ACTIVATION; DEPENDENT ERK; DEATH; INDUCTION; PROTEIN; THERAPY	Anthracycline daunorubicin (DNR) is one of the major antitumor agents widely used in the treatment of myeloid leukemia. Unfortunately, the clinical efficacy of DNR was limited because of its cytotoxity at high dosage. As a novel cytoprotective mechanism for tumor cell to survive under unfavorable conditions, autophagy has been proposed to play a role in drug resistance of tumor cells. Whether DNR can activate to impair the sensitivity of cancer cells remains unknown. Here, we first report that DNR can induce a high level of autophagy, which was associated with the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Moreover, cell death induced by DNR was greatly enhanced after autophagy inhibition by the pharmacological inhibitor chloroquine (CQ) and siRNAs targeting Atg5 and Atg7, the most important components for the formation of autophagosome. In conclusion, we found that DNR can induce cytoprotective autophagy by activation of ERK in myeloid leukemia cells. Autophagy inhibition thus represents a promising approach to improve the efficacy of DNR in the treatment of patients with myeloid leukemia.	[Han, Weidong; Wang, KaiFeng; Li, Da; Pan, Qin; Chen, Yan; Jin, Wei; Wang, Xian; Pan, Hongming] Zhejiang Univ, Coll Med, Sir Run Run Shaw Hosp, Dept Med Oncol, Hangzhou 310003, Zhejiang, Peoples R China; [Sun, Jie; Feng, Lifeng; Jin, Hongchuan] Zhejiang Univ, Coll Med, Sir Run Run Shaw Hosp, Biomed Res Ctr,Canc Biol Lab, Hangzhou 310003, Zhejiang, Peoples R China		Pan, HM (corresponding author), Zhejiang Univ, Coll Med, Sir Run Run Shaw Hosp, Dept Med Oncol, Hangzhou 310003, Zhejiang, Peoples R China.	panhongming@medmail.com.cn; jinhc@zju.edu.cn	Jin, Hongchuan/C-3686-2009	Wang, Xian/0000-0003-0041-7589; Jin, Hongchuan/0000-0002-6697-3097	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [30901740]; China National Ministry of Education [20090101120124]; Zhejiang Natural Sciences FoundationNatural Science Foundation of Zhejiang Province [Y2090166]; Science Technology Department of Zhejiang Province [2010c33168]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities	This work was supported by the National Natural Science Foundation of China (No.:30901740), China National Ministry of Education Grant (No.: 20090101120124), Zhejiang Natural Sciences Foundation Grant (No.: Y2090166) and Research Projects of Science Technology Department of Zhejiang Province (No.: 2010c33168) to WH and the Fundamental Research Funds for the Central Universities to HJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Huang, FC				Huang, Fu-Chen			The Critical Role of Membrane Cholesterol in Salmonella-Induced Autophagy in Intestinal Epithelial Cells	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						cholesterol; Salmonella; Intestine epithelia; autophagy	ENTERICA SEROVAR TYPHIMURIUM; COLON-CANCER CELLS; PROTEIN-KINASE-B; PLASMA-MEMBRANE; CROHNS-DISEASE; BECLIN 1; REGULATES AUTOPHAGY; INFECTION; PATHWAY; MACROAUTOPHAGY	It was previously observed that plasma membrane cholesterol plays a critical role in the Salmonella-induced phosphatidylinositol 3-kinase-dependent (PI3K)-dependent anti-inflammatory response in intestinal epithelial cells (IECs). The PI3K/Akt pathway is associated with autophagy which has emerged as a critical mechanism of host defense against several intracellular bacterial pathogens. Plasma membrane contributes directly to the formation of early Atg16L1-positive autophagosome precursors. Therefore, this study aimed to investigate the role of plasma membrane cholesterol on the Salmonella-induced autophagy in IECs. By using methyl-beta-cyclodextrin (MBCD), it was demonstrated that disruption of membrane cholesterol by MBCD enhanced NOD2 and Atg16L1 proteins expression in membrane, and autophagic LC3II proteins expression and LC3 punctae in Salmonella-infected Caco-2 cells, which was counteracted by Atg16L1 siRNA. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) siRNA enhanced the Salmonella-induced activation of Akt in Caco-2 cells. However, inhibitors of Akt or extracellular signal-regulated kinases (ERK) had no significant effect on Salmonella-induced autophagy Beclin 1 or LC3 proteins expression. In conclusion, our study suggests that cholesterol accumulation in the plasma membrane at the entry site of Salmonella results in the formation of Salmonella-containing vacuole (SCV) and decreased autophagy. Our results offer mechanistic insights on the critical role of membrane cholesterol in the pathogenesis of Salmonella infection in intestinal epithelial cells and the therapeutic potential of its antagonists.	[Huang, Fu-Chen] Kaohsiung Chang Gung Mem Hosp, Dept Pediat, Kaohsiung 833, Taiwan; [Huang, Fu-Chen] Chang Gung Univ, Coll Med, Kaohsiung 833, Taiwan		Huang, FC (corresponding author), Kaohsiung Chang Gung Mem Hosp, Dept Pediat, Kaohsiung 833, Taiwan.	huang817@cgmh.org.tw			National Science Council grant [NSC94-2314-B-182A-093, 100-2314-B-182-065]; Chang Gung Memorial Hospital grantChang Gung Memorial Hospital [CMRPG860431]	Funding from National Science Council grant NSC94-2314-B-182A-093 and 100-2314-B-182-065 and Chang Gung Memorial Hospital grant CMRPG860431 to F.H. is gratefully acknowledged.	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J. Mol. Sci.	JUL	2014	15	7					12558	12572		10.3390/ijms150712558			15	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	AM7ID	WOS:000340038500084	25029544	Green Published, Green Submitted, gold			2022-04-25	
J	Hongo, K; Kazama, S; Tsuno, NH; Ishihara, S; Sunami, E; Kitayama, J; Watanabe, T				Hongo, Kumiko; Kazama, Shinsuke; Tsuno, Nelson H.; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki			Immunohistochemical detection of high-mobility group box 1 correlates with resistance of preoperative chemoradiotherapy for lower rectal cancer: a retrospective study	WORLD JOURNAL OF SURGICAL ONCOLOGY			English	Article						High-mobility group box 1 (HMGB1); Lower rectal cancer; Chemoradiotherapy; Immunohistochemistry	END-PRODUCTS RAGE; COLORECTAL-CANCER; CHROMATIN PROTEIN; NECROTIC CELLS; HMGB1 RELEASE; TUMOR-GROWTH; INFLAMMATION; RECEPTOR; AUTOPHAGY; CARCINOMA	Background: High-mobility group box 1 (HMGB1) is a nucleoprotein that is related to inflammation. It has been implicated in a variety of biologically important processes, including transcription, DNA repair, differentiation, development, and extracellular signaling. Recently, its important role in the process of tumor invasion, metastasis, and resistance to anti-cancer therapies has been demonstrated. In this study, we aimed to investigate the correlation of HMGB1 expression and resistance of rectal cancer patients to chemoradiotherapy (CRT) prior to curative operation. Methods: We retrospectively reviewed the data of 75 lower rectal cancer patients without complete pathological response who had received preoperative CRT and had undergone curative resection at the University of Tokyo Hospital between May 2003 and June 2010. HMGB1 expression in surgically resected specimens was evaluated using immunohistochemical detection and specimens were classified into high or low HMGB1 expression groups. Clinicopathologic features, degree of tumor reduction, regression of tumor grade, and patient survival were compared between the groups using non-paired Student's t-tests and Kaplan-Meier analysis. Results: A total of 52 (69.3%) patients had high HMGB1 expression, and 23 (30.7%) had low expression. HMGB1 expression was significantly correlated with histologic type (P = 0.02), lymphatic invasion (P = 0.02), and venous invasion (P = 0.05). Compared to patients with low HMGB1 expression, those with high expression had a poorer response to CRT, in terms of tumor reduction ratio (42.2 versus 28.9%, respectively; P < 0.01) and post-CRT histological tumor regression grade (56.5 versus 30.8% grade 2; respectively; P = 0.03). However, no significant correlation was found between HMGB1 expression and recurrence-free and overall survival rates. Conclusions: HMGB1 expression may be one of the key factors regulating the response of rectal cancer to preoperative CRT in terms of tumor invasiveness and resistance to therapy.	[Hongo, Kumiko; Kazama, Shinsuke; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki] Univ Tokyo, Grad Sch Med, Dept Surg Oncol, Bunkyo Ku, Tokyo 1138655, Japan; [Tsuno, Nelson H.] Univ Tokyo, Grad Sch Med, Dept Transfus Med, Bunkyo Ku, Tokyo 1138655, Japan		Hongo, K (corresponding author), Univ Tokyo, Grad Sch Med, Dept Surg Oncol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.	hongokumiko-tky@umin.ac.jp					Apel A, 2008, CANCER RES, V68, P1485, DOI 10.1158/0008-5472.CAN-07-0562; Apetoh L, 2007, NAT MED, V13, P1050, DOI 10.1038/nm1622; Bartling B, 2005, CARCINOGENESIS, V26, P293, DOI 10.1093/carcin/bgh333; Belluco C, 2011, ANN SURG ONCOL, V18, P3686, DOI 10.1245/s10434-011-1822-0; Bianchi ME, 2007, J LEUKOCYTE BIOL, V81, P1, DOI 10.1189/jlb.0306164; Choi YR, 2003, CANCER RES, V63, P2188; Curtin JF, 2009, PLOS MED, V6, P83, DOI 10.1371/journal.pmed.1000010; Czura CJ, 2001, J ENDOTOXIN RES, V7, P315, DOI 10.1177/09680519010070041401; Dong XD, 2007, J IMMUNOTHER, V30, P596, DOI 10.1097/CJI.0b013e31804efc76; Ellerman JE, 2007, CLIN CANCER RES, V13, P2836, DOI 10.1158/1078-0432.CCR-06-1953; Enokido Y, 2008, BIOCHEM BIOPH RES CO, V376, P128, DOI 10.1016/j.bbrc.2008.08.108; Fiuza C, 2003, BLOOD, V101, P2652, DOI 10.1182/blood-2002-05-1300; Harris HE, 2004, EUR J IMMUNOL, V34, P1503, DOI 10.1002/eji.200424916; Huang J, 2012, CANCER RES, V72, P230, DOI 10.1158/0008-5472.CAN-11-2001; Huttunen HJ, 1999, J BIOL CHEM, V274, P19919, DOI 10.1074/jbc.274.28.19919; Ishiguro H, 2005, PROSTATE, V64, P92, DOI 10.1002/pros.20219; Levine B, 2007, NATURE, V446, P745, DOI 10.1038/446745a; Liu L, 2011, LEUKEMIA, V25, P23, DOI 10.1038/leu.2010.225; Lotze MT, 2005, NAT REV IMMUNOL, V5, P331, DOI 10.1038/nri1594; Mantovani A, 2008, NATURE, V454, P436, DOI 10.1038/nature07205; Mantovani A, 2009, NATURE, V457, P36, DOI 10.1038/457036b; Moriwaka Y, 2010, PATHOBIOLOGY, V77, P17, DOI 10.1159/000272950; Muller S, 2001, EMBO J, V20, P4337, DOI 10.1093/emboj/20.16.4337; Palumbo R, 2004, J CELL BIOL, V164, P441, DOI 10.1083/jcb.200304135; Park JS, 2006, AM J PHYSIOL-CELL PH, V290, pC917, DOI 10.1152/ajpcell.00401.2005; Qi ML, 2007, NAT CELL BIOL, V9, P402, DOI 10.1038/ncb1553; Rectum JS, 2006, GEN RULES CLIN PATHO; Rovere-Querini P, 2004, EMBO REP, V5, P825, DOI 10.1038/sj.embor.7400205; Sasahira T, 2008, CANCER SCI, V99, P1806, DOI 10.1111/j.1349-7006.2008.00894.x; Scaffidi P, 2002, NATURE, V418, P191, DOI 10.1038/nature00858; Sparvero LJ, 2009, J TRANSL MED, V7, DOI 10.1186/1479-5876-7-17; Taguchi A, 2000, NATURE, V405, P354, DOI 10.1038/35012626; Tang D, 2010, ONCOGENE, V29, P5299, DOI 10.1038/onc.2010.261; Tang DL, 2008, CRIT CARE MED, V36, P291, DOI 10.1097/01.CCM.0000295316.86942.CE; Tang DL, 2011, CELL METAB, V13, P701, DOI 10.1016/j.cmet.2011.04.008; Tang DL, 2010, BBA-GENE REGUL MECH, V1799, P131, DOI 10.1016/j.bbagrm.2009.11.014; Tsung A, 2005, J EXP MED, V201, P1135, DOI 10.1084/jem.20042614; Vakkila J, 2004, NAT REV IMMUNOL, V4, P641, DOI 10.1038/nri1415; Volp K, 2006, GUT, V55, P234, DOI 10.1136/gut.2004.062729; Wang H, 2004, J INTERN MED, V255, P320, DOI 10.1111/j.1365-2796.2003.01302.x; Wang HC, 1999, SCIENCE, V285, P248, DOI 10.1126/science.285.5425.248; Weitz J, 2005, LANCET, V365, P153, DOI 10.1016/S0140-6736(05)17706-X; *WHO, 2000, INT CLASS DIS ONC; Wittekind, 2009, TNM CLASSIFICATION M; Yang H, 2005, J LEUKOCYTE BIOL, V78, P1, DOI 10.1189/jlb.1104648; Yang H, 2004, P NATL ACAD SCI USA, V101, P296, DOI 10.1073/pnas.2434651100; Yao XJ, 2010, J CANCER RES CLIN, V136, P677, DOI 10.1007/s00432-009-0706-1; Yu W, 1997, J CELL BIOL, V137, P767, DOI 10.1083/jcb.137.3.767; Yuan FH, 2004, J BIOL CHEM, V279, P20935, DOI 10.1074/jbc.M401931200	49	14	15	0	6	BIOMED CENTRAL LTD	LONDON	236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND	1477-7819			WORLD J SURG ONCOL	World J. Surg. Oncol.	JAN 27	2015	13								7	10.1186/1477-7819-13-7			7	Oncology; Surgery	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Surgery	CB3YE	WOS:000349564600001	25622595	Green Published, gold			2022-04-25	
J	Lukovic, J; Mitrovic, MM; Popovic, S; Milosavljevic, Z; Stanojevic-Pirkovic, M; Andelkovic, M; Zelen, I; Sorak, M; Muskinja, J; Ratkovic, Z; Nikolic, IS				Lukovic, Jovan; Mitrovic, Marina M.; Popovic, Suzana; Milosavljevic, Zoran; Stanojevic-Pirkovic, Marijana; Andelkovic, Marija; Zelen, Ivanka; Sorak, Marija; Muskinja, Jovana; Ratkovic, Zoran; Nikolic, Ivana Sinisa			ANTITUMOR EFFECTS OF VANILLIN BASED CHALCONE ANALOGS IN VITRO	ACTA POLONIAE PHARMACEUTICA			English	Article						chalcones; colorectal cancer; cytotoxicity; apoptosis; autophagy	BIOLOGICAL EVALUATION; CELL-DEATH; MOLECULAR-MECHANISMS; CISPLATIN; FLAVOKAWAIN; DERIVATIVES; INHIBITION; ACTIVATION; APOPTOSIS; THERAPY	Chalcones, as a large group of organic compounds, are widely implemented in various types of anticancer therapeutics. These plant metabolites are present in fruits, vegetables, spices, and have anti-tumor, anti-inflammation, immunomodulation, antibacterial and anti-oxidative activities, as well as many other pharmacological and biological effects. The aim of the present study was to investigate cytotoxic effects, type of cell death and mechanism of action of the newly synthesized vanillin based chalcone analogs, (CH1) and (CH2) on human colon cancer HCT-116 and noncancerous (control) MRC-5 cell lines. In order to compare the effects of vanillin based chalcone analogs on investigated cell lines, as reference substances cisplatin (cisPt) and dehydrozingerone (DHZ) were used. Investigation of antitumor effect of chalcone analogs on HCT-116 cells was carried out by three methods MTT assay, flow cytometry and immunofluorescence analysis. The result of our investigation indicated that newly synthesized vanillin based chalcone analogs expressed powerful antitumor effect on cancer cells (HCT-116 cell line), while their effect on healthy cells (MRC-5 cell line) was not statistically significant. Vanillin based chalcone analogs caused overexpression and activation of mitochondrial Bax protein and caspase-3 in HCT-116 cells, indicating that their mechanism of antitumor action was mediated through activation of the inner apoptotic pathway. These results indicate possible usefulness of CH1 and CH2 in antitumor therapy whether through its direct cytotoxic effect or as adjuvant therapy. Our results indicate possible usefulness of CH1 and CH2 vanillin based chalcone analogs in antitumor therapy.	[Lukovic, Jovan; Mitrovic, Marina M.; Stanojevic-Pirkovic, Marijana; Andelkovic, Marija; Zelen, Ivanka; Nikolic, Ivana Sinisa] Univ Kragujevac, Fac Med Sci, Dept Biochem, Kragujevac, Serbia; [Popovic, Suzana] Univ Kragujevac, Fac Med Sci, Ctr Mol Med & Stem Cell Res, Dept Microbiol & Immunol, Kragujevac, Serbia; [Milosavljevic, Zoran] Univ Kragujevac, Fac Med Sci, Dept Histol & Embryol, Kragujevac, Serbia; [Sorak, Marija] Univ Kragujevac, Fac Med Sci, Dept Gynecol & Obstet, Kragujevac, Serbia; [Muskinja, Jovana; Ratkovic, Zoran] Univ Kragujevac, Fac Sci, Dept Chem, Radoja Domanovica 12,POB 60, Kragujevac 34000, Serbia		Zelen, I (corresponding author), Univ Kragujevac, Fac Med Sci, Dept Biochem, Kragujevac, Serbia.	ivanka@medf.kg.ac.rs	Suzana, Popovic/AGG-9720-2022	Nikolic, Ivana/0000-0002-1782-5506; Muskinja, Jovana/0000-0002-0638-3423; Sorak, Marija/0000-0002-3571-0091	Faculty of Medical Sciences, University of Kragujevac [JP14/17, 41010]	This study was financially supported by Faculty of Medical Sciences, University of Kragujevac (JP14/17), the project called "PrekliniEka ispitivanja bioaktivnih supstanci (PIBAS)ii, registry number 41010 and Prof. Predrag -urdjeviE for technical support.	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PHARM.	JAN-FEB	2020	77	1					57	67		10.32383/appdr/112786			11	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	KS3PX	WOS:000518225300006					2022-04-25	
J	Kazberuk, A; Zareba, I; Palka, J; Surazynski, A				Kazberuk, Adam; Zareba, Ilona; Palka, Jerzy; Surazynski, Arkadiusz			A novel plausible mechanism of NSAIDs-induced apoptosis in cancer cells: the implication of proline oxidase and peroxisome proliferator-activated receptor	PHARMACOLOGICAL REPORTS			English	Review						Cancer cells; Apoptosis; Non-steroidal anti-inflammatory drugs; Peroxisome proliferator-activated receptor; Proline dehydrogenase; Proline oxidase	NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GAMMA PPAR-GAMMA; PROLIDASE ACTIVITY; COLON-CANCER; TUMOR-SUPPRESSOR; COLLAGEN BIOSYNTHESIS; EXTRACELLULAR-MATRIX; UP-REGULATION; LUNG-CANCER; FATTY-ACIDS	Although pharmaco-epidemiological studies provided evidence for the anticancer potential of non-steroidal anti-inflammatory drugs (NSAIDs), the mechanism of their anti-cancer activity is not known. Several lines of evidence suggest that proline dehydrogenase/proline oxidase (PRODH/POX) may represent a target for NSAIDs-dependent anti-cancer activity. PRODH/POX catalyzes conversion of proline into Delta 1-pyrroline-5-carboxylate releasing ATP or reactive oxygen species for autophagy/apoptosis. Since NSAIDs are ligands of peroxisome proliferator-activated receptor (PPARs) and PPARs are implicated in PRODH/POX-dependent apoptosis we provided a hypothesis on the mechanism of NSAIDs-induced apoptosis in cancer cells.	[Kazberuk, Adam; Zareba, Ilona; Palka, Jerzy; Surazynski, Arkadiusz] Med Univ Bialystok, Dept Med Chem, Mickiewicza 2D, PL-15222 Bialystok, Poland		Surazynski, A (corresponding author), Med Univ Bialystok, Dept Med Chem, Mickiewicza 2D, PL-15222 Bialystok, Poland.	kadam568@gmail.com; ilona.zareba@gmail.com; pal@umb.edu.pl; arek@umb.edu.pl	Surażynski, Arkadiusz/ABG-2795-2020; Zareba, Ilona/T-6930-2018	Surażynski, Arkadiusz/0000-0003-4475-873X; Zareba, Ilona/0000-0002-7934-6973; Kazberuk, Adam/0000-0002-8485-6505	National Science CentreNational Science Centre, Poland [2017/27/N/NZ7/02370]	This research was supported by the National Science Centre, Grant number 2017/27/N/NZ7/02370.	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Rep.	OCT	2020	72	5					1152	1160		10.1007/s43440-020-00140-z		JUL 2020	9	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	OI4ND	WOS:000556131300001	32710395	Green Published, hybrid			2022-04-25	
J	Wang, LH; Huang, WD; Zhan, JC				Wang, Lihua; Huang, Weidong; Zhan, Jicheng			Grape Seed Proanthocyanidins Induce Autophagy and Modulate Survivin in HepG2 Cells and Inhibit Xenograft Tumor Growth in Vivo	NUTRIENTS			English	Article						hepatocellular carcinoma; HepG2 cells; grape seed proanthocyanidins; autophagy; survivin; xenograft	COLON-CANCER CELLS; APOPTOSIS; EXTRACT; VITRO; GENE; GENERATION; PREVENTION; THERAPY; DEATH	Liver cancer is one of the leading causes of death worldwide. Although radiotherapy and chemotherapy are effective in general, they present various side effects, significantly limiting the curative effect. Increasing evidence has shown that the dietary intake of phytochemicals plays an essential role in the chemoprevention or chemotherapy of tumors. In this work, HepG2 cells and nude mice with HepG2-derived xenografts were treated with grape seed proanthocyanidins (GSPs). The results showed that GSPs induced autophagy, and inhibition of autophagy increased apoptosis in HepG2 cells. In addition, GSPs also reduced the expression of survivin. Moreover, survivin was involved in GSPs-induced apoptosis. GSPs at 100 mg/kg and 200 mg/kg significantly inhibited the growth of HepG2 cells in nude mice without causing observable toxicity and autophagy, while inducing the phosphorylation of mitogen-activated protein kinase (MAPK) pathway-associated proteins, p-JNK, p-ERK and p-p38 MAPK and reducing the expression of survivin. These results suggested that GSPs might be promising phytochemicals against liver cancer.	[Wang, Lihua; Huang, Weidong; Zhan, Jicheng] China Agr Univ, Beijing Key Lab Viticulture & Enol, Coll Food Sci & Nutr Engn, Beijing 100083, Peoples R China		Zhan, JC (corresponding author), China Agr Univ, Beijing Key Lab Viticulture & Enol, Coll Food Sci & Nutr Engn, Beijing 100083, Peoples R China.	lihuawang@cau.edu.cn; huanggwd@263.net; zhanjicheng@cau.edu.cn	Zhan, Jicheng/ABF-8501-2021		National Key Research and Development Program of China [2017YFD0401202]	This work was supported by The National Key Research and Development Program of China (2017YFD0401202).	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J	Morselli, E; Shen, SS; Ruckenstuhl, C; Bauer, MA; Marino, G; Galluzzi, L; Criollo, A; Michaud, M; Maiuri, MC; Chano, T; Madeo, F; Kroemer, G				Morselli, Eugenia; Shen, Shensi; Ruckenstuhl, Christoph; Bauer, Maria Anna; Marino, Guillermo; Galluzzi, Lorenzo; Criollo, Alfredo; Michaud, Mickael; Maiuri, Maria Chiara; Chano, Tokuhiro; Madeo, Frank; Kroemer, Guido			p53 inhibits autophagy by interacting with the human ortholog of yeast Atg17, RB1CC1/FIP200	CELL CYCLE			English	Article						aging; longevity; mTOR; rapamycin; Saccharomyces cerevisiae	LIFE-SPAN EXTENSION; HUMAN BREAST-CANCER; CYTOPLASMIC P53; FIP200; CELLS; LONGEVITY; APOPTOSIS; COMPLEX; PATHWAYS; PROTEIN	The tumor suppressor protein p53 tonically suppresses autophagy when it is present in the cytoplasm. This effect is phylogenetically conserved from mammals to nematodes, and human p53 can inhibit autophagy in yeast, as we show here. Bioinformatic investigations of the p53 interactome in relationship to the autophagy-relevant protein network underscored the possible relevance of a direct molecular interaction between p53 and the mammalian ortholog of the essential yeast autophagy protein Atg17, namely RB1-inducible coiled-coil protein 1 (RB1CC1), also called FAK family kinase-interacting protein of 200 KDa (FIP200). Mutational analyses revealed that a single point mutation in p53 (K382R) abolished its capacity to inhibit autophagy upon transfection into p53-deficient human colon cancer or yeast cells. In conditions in which wild type p53 co-immunoprecipitated with RB1CC1/FIP200, p53(K382R) failed to do so, underscoring the importance of the physical interaction between these proteins for the control of autophagy. In conclusion, p53 regulates autophagy through a direct molecular interaction with RB1CC1/FIP200, a protein that is essential for the very apical step of autophagy initiation.	[Morselli, Eugenia; Shen, Shensi; Marino, Guillermo; Galluzzi, Lorenzo; Criollo, Alfredo; Michaud, Mickael; Maiuri, Maria Chiara; Kroemer, Guido] INSERM, U848, Paris, France; [Morselli, Eugenia; Shen, Shensi; Marino, Guillermo; Galluzzi, Lorenzo; Criollo, Alfredo; Michaud, Mickael; Maiuri, Maria Chiara; Kroemer, Guido] Inst Gustave Roussy, Paris, France; [Morselli, Eugenia; Shen, Shensi; Marino, Guillermo; Galluzzi, Lorenzo; Criollo, Alfredo; Michaud, Mickael; Maiuri, Maria Chiara] Univ Paris 11, Paris, France; [Ruckenstuhl, Christoph; Bauer, Maria Anna; Madeo, Frank] Graz Univ, Inst Mol Biosci, Graz, Austria; [Ruckenstuhl, Christoph] Med Univ Graz, Inst Pathol, Graz, Austria; [Chano, Tokuhiro] Shiga Univ Med Sci, Dept Clin Lab Med, Shiga, Japan; [Kroemer, Guido] Ctr Rech Cordeliers, Paris, France; [Kroemer, Guido] Univ Paris 05, Paris, France; [Kroemer, Guido] Hop Europeen Georges Pompidou, Paris, France; [Kroemer, Guido] Inst Gustave Roussy, Villejuif, France		Kroemer, G (corresponding author), INSERM, U848, Paris, France.	kroemer@orange.fr	Kroemer, Guido/AAY-9859-2020; GARCÍA, GUILLERMO MARIÑO/J-1726-2012; KROEMER, Guido/B-4263-2013; Galluzzi, Lorenzo/AAH-3286-2021; SHEN, Shensi/AAW-2735-2020; Galluzzi, Lorenzo/AAG-6294-2019; Galluzzi, Lorenzo/K-2709-2012; GARCÍA, GUILLERMO MARIÑO/AAI-8015-2020; Chano, Tokuhiro/F-5816-2018; Galluzzi, Lorenzo/AAG-6432-2019	GARCÍA, GUILLERMO MARIÑO/0000-0003-1960-1677; KROEMER, Guido/0000-0002-9334-4405; SHEN, Shensi/0000-0002-5087-8220; Galluzzi, Lorenzo/0000-0003-2257-8500; Chano, Tokuhiro/0000-0002-9959-1183; Bauer, Maria A./0000-0003-3211-0434; Madeo, Frank/0000-0002-5070-1329; Ruckenstuhl, Christoph/0000-0002-4338-4679; Criollo, Alfredo/0000-0002-2737-7751	Ligue Nationale contre le Cancer (Equipes labelisee); Agence Nationale pour la Recherche (ANR)French National Research Agency (ANR); European CommissionEuropean CommissionEuropean Commission Joint Research Centre; Fondation pour la Recherche Medicale (FRM)Fondation pour la Recherche Medicale; Institut National du Cancer (INCa)Institut National du Cancer (INCA) France; Fondation Bettencourt-Schueller; Canceropole Ile-de-FranceRegion Ile-de-France; AXA Chair for Longevity Research; Austrian Science Fund FWF (Austria)Austrian Science Fund (FWF) [P23490]	We thank Dr. Wei Gu for providing the p53 plasmids. G.K. is supported by the Ligue Nationale contre le Cancer (Equipes labelisee), Agence Nationale pour la Recherche (ANR), European Commission (Active p53, Apo-Sys, ChemoRes, ApopTrain, ArtForce), Fondation pour la Recherche Medicale (FRM), Institut National du Cancer (INCa), Fondation Bettencourt-Schueller, Canceropole Ile-de-France, and the AXA Chair for Longevity Research. F.M. is supported by the Austrian Science Fund FWF (Austria, grant P23490), and the European Commission (Apo-Sys).	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J	Kim, JC; Ha, YJ; Tak, KH; Roh, SA; Kwon, YH; Kim, CW; Yoon, YS; Lee, JL; Park, Y; Kim, SK; Kim, SY; Cho, DH; Kim, YS				Kim, Jin Cheon; Ha, Ye Jin; Tak, Ka Hee; Roh, Seon Ae; Kwon, Yi Hong; Kim, Chan Wook; Yoon, Yong Sik; Lee, Jong Lyul; Park, Yangsoon; Kim, Seon-Kyu; Kim, Seon-Young; Cho, Dong-Hyung; Kim, Yong Sung			Opposite functions of GSN and OAS2 on colorectal cancer metastasis, mediating perineural and lymphovascular invasion, respectively	PLOS ONE			English	Article							MESENCHYMAL TRANSITION; PROGNOSTIC-FACTOR; EXPRESSION; AUTOPHAGY; COLON; GELSOLIN; GROWTH; SYNTHETASE; ACTIVATION; SUPPRESSOR	The present study aimed to identify molecules associated with lymphovascular invasion (LVI) and perineural invasion (PNI) and to examine their biological behavior in colorectal cancer (CRC). LVI- and PNI-associated molecules were identified and verified using sequential processes including (1) identification of 117 recurrence-associated genes differentially expressed on RNA-seq analysis using primary cancer tissues from 130 CRC patients with and without systemic recurrence; (2) analysis of molecules associated with LVI and PNI; (3) assessment of biological properties by measuring proliferation, anoikis, invasion/migration, epithelial-mesenchymal transition and autophagy flux; and (4) verification of disease-free survival using public datasets. Gelsolin (GSN) and 2'-5'-oligoadenylate synthetase 2 (OAS2) were associated with PNI and LVI, respectively. Invasion potential was >2-fold greater in GSN-overexpressing LoVo cells than in control cells (p<0.001-0.005), whereas OAS2-overexpressing RKO cells showed reduced invasion (p<0.001-0.005). GSN downregulated E-cadherin, beta-catenin, claudin-1 and snail, and upregulated N-cadherin and ZEB1, whereas OAS2 overexpression had the opposite effects. Several autophagy-related proteins including ATG5-12, ATG6/BECN1, ATG7 and ATG101 were downregulated in GSN-overexpressing LoVo cells, whereas the opposite pattern was observed in OAS2-overexpressing RKO cells. Patients with low GSN expression had significantly higher 5-year recurrence-free survival (RFS) rates than those with GSN overexpression (73.6% vs. 64.7%, p = 0.038), whereas RFS was longer in patients with OAS2 overexpression than in those with underexpression (73.4% vs. 63.7%, p = 0.01). In conclusion, GSN and OAS2 were positively and negatively associated with recurrence, respectively, suggesting their potential value as predictors of recurrence or therapeutic targets in CRC patients.	[Kim, Jin Cheon; Ha, Ye Jin; Tak, Ka Hee; Roh, Seon Ae; Kwon, Yi Hong; Kim, Chan Wook; Yoon, Yong Sik; Lee, Jong Lyul] Univ Ulsan, Dept Surg, Coll Med, Seoul, South Korea; [Kim, Jin Cheon; Ha, Ye Jin; Tak, Ka Hee; Roh, Seon Ae; Kwon, Yi Hong; Kim, Chan Wook; Yoon, Yong Sik; Lee, Jong Lyul; Park, Yangsoon; Kim, Seon-Kyu; Kim, Seon-Young; Cho, Dong-Hyung; Kim, Yong Sung] Asan Med Ctr, Inst Innovat Canc Res, Seoul, South Korea; [Park, Yangsoon] Univ Ulsan, Dept Pathol, Coll Med, Seoul, South Korea; [Kim, Seon-Kyu; Kim, Seon-Young; Kim, Yong Sung] Korea Res Inst Biosci & Biotechnol, Med Genom Res Ctr, Daejeon, South Korea; [Cho, Dong-Hyung] Kyungpook Natl Univ, Sch Life Sci, Daegu, South Korea		Kim, JC (corresponding author), Univ Ulsan, Dept Surg, Coll Med, Seoul, South Korea.; Kim, JC; Cho, DH; Kim, YS (corresponding author), Asan Med Ctr, Inst Innovat Canc Res, Seoul, South Korea.; Kim, YS (corresponding author), Korea Res Inst Biosci & Biotechnol, Med Genom Res Ctr, Daejeon, South Korea.; Cho, DH (corresponding author), Kyungpook Natl Univ, Sch Life Sci, Daegu, South Korea.	jckim@amc.seoul.kr; chodong03@gmail.com; yongsung@kribb.re.kr	Lww, Jong Lyul/W-1791-2019	Lww, Jong Lyul/0000-0002-5878-8000; Kim, Seon-Kyu/0000-0002-4176-5187	Korea Research FoundationKorea Research Foundation [2016R1E1A1A02919844, 2017R1A2B1009062]; Ministry of Science, ICT, and Future Planning, Republic of Korea	This work was supported by grants from the Korea Research Foundation (2016R1E1A1A02919844 to JCK and 2017R1A2B1009062 to SAR), Ministry of Science, ICT, and Future Planning, Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Chen, RJ; Tsai, SJ; Ho, CT; Pan, MH; Ho, YS; Wu, CH; Wang, YJ				Chen, Rong-Jane; Tsai, Shang-Jie; Ho, Chi-Tang; Pan, Min-Hsiung; Ho, Yuan-Soon; Wu, Chih-Hsiung; Wang, Ying-Jan			Chemopreventive Effects of Pterostilbene on Urethane-Induced Lung Carcinogenesis in Mice via the Inhibition of EGFR-Mediated Pathways and the Induction of Apoptosis and Autophagy	JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY			English	Article						chemopreventive; pterostilbene; urethane; EGFR; autophagy	SIGNAL-TRANSDUCTION PATHWAYS; NF-KAPPA-B; COLON CARCINOGENESIS; CELL-CYCLE; CANCER; MUTATIONS; ADENOCARCINOMA; PROLIFERATION; ANTIOXIDANT; BLUEBERRIES	Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer deaths globally. Due to the lack of successful chemopreventive agents for lung cancer, there is an emerging need to evaluate new and effective agents for lung cancer prevention. Pterostilbene, a naturally occurring analogue of resveratrol, has been reported to be an effective chemopreventive agent against many cancers. The aim of this study is to investigate the chemopreventive effects of pterostilbene in urethane-induced murine lung tumors. Pretreatment with pterostilbene at 50 or 250 mg/kg significantly reduced tumor multiplicity by 26 and 49%, respectively. Pterostilbene also significantly inhibited tumor volume by 25 and 34% and decreased the tumor burden per mouse by 45 and 63%, respectively. The Mechanisms by which pterostilbene suppresses lung tumorigenesis have been investigated in lung tissues and homogenates. The results indicate that the pterostilbene-mediated chemopreventive effects in vivo were a result of the inhibition of epidermal growth factor receptor (EGFR) and its downstream pathways, leading to retarded cell cycle progression, and of the induction of apoptosis and autophagy during urethane-induced lung tumorigenesis.	[Chen, Rong-Jane; Tsai, Shang-Jie; Wang, Ying-Jan] Natl Cheng Kung Univ, Coll Med, Dept Environm & Occupat Hlth, Tainan 70428, Taiwan; [Chen, Rong-Jane] Taipei Med Univ, Grad Inst Clin Med, Taipei, Taiwan; [Ho, Chi-Tang] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08903 USA; [Pan, Min-Hsiung] Natl Kaohsiung Marine Univ, Dept Seafood Sci, Kaohsiung, Taiwan; [Ho, Yuan-Soon] Taipei Med Univ, Sch Med Technol & Biotechnol, Taipei, Taiwan; [Ho, Yuan-Soon; Wu, Chih-Hsiung] Taipei Med Univ, Ctr Excellence Canc Res, Taipei, Taiwan; [Wu, Chih-Hsiung] Taipei Med Univ, Shuang Ho Hosp, Sch Med, Dept Surg, Taipei, Taiwan		Wu, CH (corresponding author), Taipei Med Univ, Shuang Ho Hosp, Sch Med, Dept Surg, 291 Jhongjheng Rd, Jhonghe City 23561, Taipei County, Taiwan.	chwu@tmu.edu.tw; yjwang@mail.ncku.edu.tw	Pan, Min-Hsiung/AAT-8865-2021	Pan, Min-Hsiung/0000-0002-5188-7030	National Science CouncilMinistry of Science and Technology, Taiwan [NSC 100-2314-B-006-055]; Food and Drug Administration, Department of Health, Executive Yuan [DOH101-FDA-41301]; Taipei Medical University, Center of Excellence for Cancer Research (TMU-CECR) [DOH101-TD-C-111-008]	We thank the commission of this study by the National Science Council (NSC 100-2314-B-006-055), Food and Drug Administration, Department of Health, Executive Yuan (DOH101-FDA-41301), and Taipei Medical University, Center of Excellence for Cancer Research (TMU-CECR, DOH101-TD-C-111-008), for their support.	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Agric. Food Chem.	NOV 21	2012	60	46					11533	11541		10.1021/jf302778a			9	Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Agriculture; Chemistry; Food Science & Technology	040LY	WOS:000311325300009	23113763				2022-04-25	
J	Zorc, B; Rajic, Z; Perkovic, I				Zorc, Branka; Rajic, Zrinka; Perkovic, Ivana			Antiproliferative evaluation of various aminoquinoline derivatives	ACTA PHARMACEUTICA			English	Article						primaquine; chloroquine; mefloquine; fumardiamide; antiproliferative activity	LUNG-CANCER CELLS; PRIMAQUINE DERIVATIVES; SUBSTITUENTS SYNTHESIS; ANTIMALARIAL-DRUGS; CHLOROQUINE; AUTOPHAGY; UREA; ANTIMYCOBACTERIAL; UREIDOAMIDES; ARTEMISININ	Four classes of aminoquinoline derivatives were prepared: primaquine ureas 1a-f, primaquine bis-ureas 2a-f, chloroquine fumardiamides 3a-f and mefloquine fumardiamides 4a-f. Their antiproliferative activities against breast adenocarcinoma (MCF-7), lung carcinoma (H460) and colon carcinoma (HCT 116 and SW620) cell lines were evaluated in vitro, using MTT cell proliferation assay. The results revealed a low activity of primaquine urea and bis-urea derivatives and high activity of all fumardiamides, with IC50 values in low micromolar range against all tested cancer cell lines.	[Zorc, Branka; Rajic, Zrinka; Perkovic, Ivana] Univ Zagreb, Fac Pharm & Biochem, Dept Med Chem, Zagreb 10000, Croatia		Zorc, B (corresponding author), Univ Zagreb, Fac Pharm & Biochem, Dept Med Chem, Zagreb 10000, Croatia.	bzorc@pharma.hr			Croatian Science Foundation [IP-2014-09-1501]	The study was supported by the Croatian Science Foundation (research project IP-2014-09-1501). We thank Katja Ester, Lidija Uzelac and Marijeta Kralj for antiproliferative screening and Toma Keser for the experiments with glutathione.	Abdel-aziz A K, 2014, SCI P, V1, pe384, DOI DOI 10.14800/SP.384; Abdel-Aziz AK, 2014, CHEM-BIOL INTERACT, V217, P28, DOI 10.1016/j.cbi.2014.04.007; Ashburn TT, 2004, NAT REV DRUG DISCOV, V3, P673, DOI 10.1038/nrd1468; Avery MA, 2016, REFERENCE MODULE CHE, DOI [10.1016/B978-0-12-409547-2.11056-X, DOI 10.1016/B978-0-12-409547-2.11056-X]; Beus M., 2019, 6 CROAT C PHARM INT; Beus M, 2019, ACTA PHARMACEUT, V69, P233, DOI 10.2478/acph-2019-0019; Beus M, 2018, CHEMISTRYOPEN, V7, P624, DOI 10.1002/open.201800117; Choi AR, 2016, ANTICANCER RES, V36, P1641; Duffy R, 2012, DRUG DISCOV TODAY, V17, P942, DOI 10.1016/j.drudis.2012.03.013; Dzimbeg G, 2008, EUR J MED CHEM, V43, P1180, DOI 10.1016/j.ejmech.2007.09.001; Fernandes I, 2009, BIOORG MED CHEM LETT, V19, P6914, DOI 10.1016/j.bmcl.2009.10.081; Flanagan ME, 2014, J MED CHEM, V57, P10072, DOI 10.1021/jm501412a; Ganguli A, 2014, BIOCHIMIE, V107, P338, DOI 10.1016/j.biochi.2014.10.001; Kimura T, 2013, CANCER RES, V73, P3, DOI 10.1158/0008-5472.CAN-12-2464; Levatic J, 2018, EUR J MED CHEM, V146, P651, DOI 10.1016/j.ejmech.2018.01.062; Liu F, 2014, ACTA PHARMACOL SIN, V35, P645, DOI 10.1038/aps.2014.3; Liu LK, 2018, ONCOL REP, V39, P2807, DOI 10.3892/or.2018.6363; Martirosyan AR, 2004, BIOCHEM PHARMACOL, V68, P1729, DOI 10.1016/j.bcp.2004.05.003; Njaria PM, 2015, EXPERT OPIN THER PAT, V25, P1003, DOI 10.1517/13543776.2015.1050791; Oprea TI, 2012, AAPS J, V14, P759, DOI 10.1208/s12248-012-9390-1; Pavic K, 2014, EUR J MED CHEM, V86, P502, DOI 10.1016/j.ejmech.2014.09.013; Pavic K, 2019, MOL DIVERS, V23, P657, DOI 10.1007/s11030-018-9899-z; Pavic K, 2018, ACTA PHARMACEUT, V68, P471, DOI 10.2478/acph-2018-0039; Pavic K, 2018, EUR J MED CHEM, V143, P769, DOI 10.1016/j.ejmech.2017.11.083; Pavic K, 2016, MOLECULES, V21, DOI 10.3390/molecules21121629; Perkovic I, 2016, EUR J MED CHEM, V124, P622, DOI 10.1016/j.ejmech.2016.08.021; Perkovic I, 2013, J ENZYM INHIB MED CH, V28, P601, DOI 10.3109/14756366.2012.663366; Rajic Z, 2018, MOLECULES, V23, DOI 10.3390/molecules23071724; Rossi T, 2007, ANTICANCER RES, V27, P2555; Simunovic M, 2009, BIOORGAN MED CHEM, V17, P5605, DOI 10.1016/j.bmc.2009.06.030; Solomon VR, 2009, EUR J PHARMACOL, V625, P220, DOI 10.1016/j.ejphar.2009.06.063; Soo GW, 2010, ANTI-CANCER DRUG, V21, P695, DOI 10.1097/CAD.0b013e32833c93b3; Vale N, 2009, EUR J MED CHEM, V44, P937, DOI 10.1016/j.ejmech.2008.08.011; van Huijsduijnen RH, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0082962; Verbaanderd C, 2017, ECANCERMEDICALSCIENC, V11, DOI 10.3332/ecancer.2017.781; Vlainic J, 2018, J ENZYM INHIB MED CH, V33, P376, DOI 10.1080/14756366.2017.1423067; Wang F, 2018, CELL PHYSIOL BIOCHEM, V45, P54, DOI 10.1159/000486222; Wong YK, 2017, MED RES REV, V37, P1492, DOI 10.1002/med.21446; Yeo SJ, 2017, MALARIA J, V16, DOI 10.1186/s12936-017-1725-z; Zhang I, 2018, CELL DEATH DISCOV, V4, DOI 10.1038/s41420-018-0103-0	40	0	0	0	2	HRVATSKO FARMACEUTSKO DRUSTOV (HFD)-CROATION PHARMACEUTICAL SOC	ZAGREB	MASARYKOVA 2, 10000 ZAGREB, CROATIA	1330-0075	1846-9558		ACTA PHARMACEUT	Acta Pharm.	DEC	2019	69	4					661	672		10.2478/acph-2019-0048			12	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	JJ1BS	WOS:000493896000014	31639093	Green Published, gold			2022-04-25	
J	Cruickshanks, N; Roberts, JL; Bareford, MD; Tavallai, M; Poklepovic, A; Booth, L; Spiegel, S; Dent, P				Cruickshanks, Nichola; Roberts, Jane L.; Bareford, M. Danielle; Tavallai, Mehrad; Poklepovic, Andrew; Booth, Laurence; Spiegel, Sarah; Dent, Paul			Differential regulation of autophagy and cell viability by ceramide species	CANCER BIOLOGY & THERAPY			English	Article						FTY720; Gilenya; Pemetrexed; Alimta; ceramide; S1P; autophagy; CerS2; CerS6	SPHINGOSINE KINASE TYPE-2; FTY720 INDUCES APOPTOSIS; CANCER-CELLS; CARCINOMA CELLS; IMMUNOSUPPRESSANT FTY720; GLIOBLASTOMA-MULTIFORME; TUMOR SUPPRESSION; DRUG FTY720; H-RAS; ACTIVATION	The present studies sought to determine whether the anti-folate pemetrexed (Alimta) and the sphingosine-1-phosphate receptor modulator FTY720 (Fingolimod, Gilenya) interacted to kill tumor cells. FTY720 and pemetrexed interacted in a greater than additive fashion to kill breast, brain and colorectal cancer cells. Loss of p53 function weakly enhanced the toxicity of FTY720 whereas deletion of activated RAS strongly or expression of catalytically inactive AKT facilitated killing. Combined drug exposure reduced the activity of AKT, p70 S6K and mTOR and activated JNK and p38 MAPK. Expression of activated forms of AKT, p70 S6K and mTOR or inhibition of JNK and p38 MAPK suppressed the interaction between FTY720 and pemetrexed. Treatment of cells with FTY720 and pemetrexed increased the numbers of early autophagosomes but not autolysosomes, which correlated with increased LC3II processing and increased p62 levels, suggestive of stalled autophagic flux. Knock down of ATG5 or Beclin1 suppressed autophagosome formation and cell killing. Knock down of ceramide synthase 6 suppressed autophagosome production and cell killing whereas knock down of ceramide synthase 2 enhanced vesicle formation and facilitated death. Collectively our findings argue that pemetrexed and FTY720 could be a novel adjunct modality for breast cancer treatment.	[Cruickshanks, Nichola; Roberts, Jane L.; Bareford, M. Danielle; Tavallai, Mehrad; Booth, Laurence; Spiegel, Sarah; Dent, Paul] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23284 USA; [Poklepovic, Andrew] Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA		Dent, P (corresponding author), Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23284 USA.	pdent@vcu.edu			PHS from the National Institutes of Health [R01-CA141704, R01-CA150214, R01-DK52825, R01-CA61774]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA016059] Funding Source: NIH RePORTER	Support for the present study was funded from PHS grants from the National Institutes of Health [R01-CA141704, R01-CA150214, R01-DK52825, R01-CA61774].	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Ther.	MAY	2015	16	5					733	742		10.1080/15384047.2015.1026509			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CI7XY	WOS:000354981300013	25803131	Green Published, Bronze			2022-04-25	
J	Chandrika, BB; Maney, SK; Lekshmi, SU; Joseph, J; Seervi, M; Praveen, KS; Santhoshkumar, TR				Chandrika, Bhavya Balan; Maney, Sathish Kumar; Lekshmi, Swathi U.; Joseph, Jeena; Seervi, Mahendra; Praveen, K. S.; Santhoshkumar, T. R.			Bax deficiency mediated drug resistance can be reversed by endoplasmic reticulum stress induced death signaling	BIOCHEMICAL PHARMACOLOGY			English	Article						Drug resistance; ER stress; Bax mutation; Apoptosis; Autophagy	MICROSATELLITE MUTATOR PHENOTYPE; PROAPOPTOTIC GENE BAX; CYTOCHROME-C RELEASE; MUTATIONAL INACTIVATION; APOPTOTIC RESPONSE; COLORECTAL CANCERS; SOLID TUMORS; MITOCHONDRIA; ACTIVATION; PROTEINS	Tumors often acquire drug resistance due to functional loss of pro apoptotic gene Bax, a critical and essential component of cell death rendering them insensitive to most anti-tumor agents. Compounds that can induce Bax independent apoptotic cell death are expected to overcome such drug resistance. We have employed a live cell based screening platform to identify potential compounds that can induce programmed cell death in Bax deficiency. Release of cytochrome C from mitochondria into the cytosol is a decisive initial event required for the caspase dependent cell death. We have engineered both wild type and Bax knock out colon cancer cells stably expressing cytochrome C with EGFP fusion protein to identify compounds that can trigger cytochrome C release in both cells with equal efficiency. In the fluorescent translocation assay, most of the drugs tested failed to induce cytochrome C release in Bax deficient cells validating the sensitivity of the assay. This study identified five lead compounds such as thapsigargin, tunicamycine, MG132, kaempferol and camptothecin that could induce cytochrome C release in both wild type and Bax deficient cells with equal potency. All the positive hits induced ER stress signaling as evidenced by up-regulation of Grp78. Studies with a Bak deficient cells indicate that Bak deficiency confers protection to cells from ER stress through autophagy. Further studies revealed that ER stress inducing agents are capable of triggering classical mitochondrial apoptotic cell death through the conformational activation of Bak, substantiating the potential of this pathway in designing drugs against Bax deficiency mediated drug resistance. (C) 2010 Elsevier Inc. All rights reserved.	[Chandrika, Bhavya Balan; Maney, Sathish Kumar; Lekshmi, Swathi U.; Joseph, Jeena; Seervi, Mahendra; Praveen, K. S.; Santhoshkumar, T. R.] Rajiv Gandhi Ctr Biotechnol, Integrated Canc Res, Trivandrum 695014, Kerala, India		Santhoshkumar, TR (corresponding author), Rajiv Gandhi Ctr Biotechnol, Integrated Canc Res, Trivandrum 695014, Kerala, India.	trsanthosh@rgcb.res.in	Seervi, Mahendra/K-8812-2019	Seervi, Mahendra/0000-0002-0266-2062	Department of Biotechnology; Department of Science and Technology, University Grant CommissionDepartment of Science & Technology (India)University Grants Commission, India; International Foundation of Science (Sweden)International Foundation for Science	This work was supported by funding from Department of Biotechnology (IYBA Award), Department of Science and Technology, University Grant Commission, and International Foundation of Science (Sweden).	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J	Zhou, Y; Yang, LP; Xiong, L; Wang, KP; Hou, XY; Li, QL; Kong, FH; Liu, X; He, J				Zhou, Yan; Yang, Leping; Xiong, Li; Wang, Kunpeng; Hou, Xuyang; Li, Qinglong; Kong, Fanhua; Liu, Xi; He, Jun			KIF11 is upregulated in colorectal cancer and silencing of it impairs tumor growth and sensitizes colorectal cancer cells to oxaliplatin via p53/GSK3 beta signaling	JOURNAL OF CANCER			English	Article						KIF11; colorectal cancer; oxaliplatin; autophagy; GSK3 beta	CLINICAL-PRACTICE GUIDELINES; BREAST-CANCER; KINESIN SUPERFAMILY; RECTAL-CANCER; PHASE-I; INHIBITOR; EXPRESSION; AUTOPHAGY; TRIAL	Colorectal cancer (CRC) is the most frequently diagnosed cancer of the digestive tract. Chemotherapy drugs such as oxaliplatin are frequently administered to CRC patients diagnosed with advanced or metastatic disease. A deep understanding of the molecular mechanism underlying CRC tumorigenesis and identification of optimal biomarkers for estimating chemotherapy sensitivity are essential for the treatment of CRC. Numerous members of the kinesin family are dysregulated in cancers, contributing to tumorigenesis, metastasis and drug resistance. KIF11 is a key component of the bipolar spindle and is highly expressed in several cancer types. We analyzed KIF11 expression in clinical samples by Western blotting and qRT-PCR and explored its role and mechanism in CRC growth and sensitivity to oxaliplatin via detection of the phosphorylation profile of kinases and gain-and-loss-of-function assays. We found that KIF11 was upregulated in CRC tissues and was associated with advanced clinical stage and vessel invasion and that knockdown of KIF11 led to tumor growth arrest and increased sensitivity to oxaliplatin via enhanced DNA damage and apoptosis. Mechanistically, aberrantly activated p53 signaling or possibly deactivated GSK3 beta signaling was responsible for KIF11 knockdown-mediated effects in CRC cells. Thus, our data firmly demonstrated that KIF11 could serve as a potential oncogene and proper biomarker for assessing oxaliplatin sensitivity in CRC.	[Zhou, Yan; Yang, Leping; Xiong, Li; Hou, Xuyang; Li, Qinglong; Kong, Fanhua; Liu, Xi; He, Jun] Cent South Univ, Xiangya Hosp2, Dept Gen Surg, Changsha 410011, Hunan, Peoples R China; [Wang, Kunpeng] Taizhou Univ Hosp, Taizhou Cent Hosp, Dept Gen Surg, Taizhou 318000, Zhejiang, Peoples R China		He, J (corresponding author), Cent South Univ, Xiangya Hosp2, Dept Gen Surg, Changsha 410011, Hunan, Peoples R China.	junjunhe@csu.edu.cn					Ahmed SM, 2012, J CELL BIOL, V199, P951, DOI 10.1083/jcb.201206051; Amaravadi RK, 2019, CANCER DISCOV, V9, P1167, DOI 10.1158/2159-8290.CD-19-0292; Asbaghi Y, 2017, GENE CHROMOSOME CANC, V56, P668, DOI 10.1002/gcc.22471; Benson A, 2018, J NATL COMPR CANC NE, V16, P874, DOI 10.6004/jnccn.2018.0061; Benson AB, 2017, J NATL COMPR CANC NE, V15, P370, DOI 10.6004/jnccn.2017.0036; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Burris HA, 2011, INVEST NEW DRUG, V29, P467, DOI 10.1007/s10637-009-9374-x; Cao YN, 2018, EUR J MED CHEM, V143, P806, DOI 10.1016/j.ejmech.2017.11.062; Chen FJ, 2019, NAT COMMUN, V10, DOI 10.1038/s41467-019-13528-0; Chen JX, 2016, GUT, V65, P1522, DOI 10.1136/gutjnl-2015-310625; Chen WQ, 2016, CA-CANCER J CLIN, V66, P115, DOI 10.3322/caac.21338; Chung V, 2012, CANCER CHEMOTH PHARM, V69, P733, DOI 10.1007/s00280-011-1756-z; Corson TW, 2006, INT J CANCER, V119, P1088, DOI 10.1002/ijc.21954; Daigo K, 2018, INT J ONCOL, V52, P155, DOI 10.3892/ijo.2017.4181; De S, 2009, CANCER RES, V69, P8035, DOI 10.1158/0008-5472.CAN-09-1224; Du WQ, 2016, DEV CELL, V37, P326, DOI 10.1016/j.devcel.2016.04.014; Duan Y, 2016, NAT COMMUN, V7, DOI 10.1038/ncomms12648; Gnjatic S, 2010, INT J CANCER, V127, P381, DOI 10.1002/ijc.25058; Goodson HV, 2018, CSH PERSPECT BIOL, V10, DOI 10.1101/cshperspect.a022608; Hou PF, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0550-9; Imai T, 2017, ANTICANCER RES, V37, P47, DOI 10.21873/anticanres.11287; Infante JR, 2012, CANCER CHEMOTH PHARM, V69, P165, DOI 10.1007/s00280-011-1667-z; Jackson JR, 2007, NAT REV CANCER, V7, P107, DOI 10.1038/nrc2049; Jungwirth G, 2019, CANCERS, V11, DOI 10.3390/cancers11040545; Kantarjian HM, 2012, INVEST NEW DRUG, V30, P1107, DOI 10.1007/s10637-011-9660-2; Kong FH, 2020, INT J BIOCHEM CELL B, V122, DOI 10.1016/j.biocel.2020.105731; Kwak EL, 2010, NEW ENGL J MED, V363, P1693, DOI 10.1056/NEJMoa1006448; Li YJ, 2017, CHIN J CANCER, V52, DOI 10.1186/s40880-017-0219-2; Liang Y, 2017, CANCER RES, V77, P5479, DOI 10.1158/0008-5472.CAN-17-0496; Lin JT, 2020, BBA-MOL CELL RES, V1867, DOI 10.1016/j.bbamcr.2020.118659; Liu T, 2020, FRONT PHARMACOL, V11, DOI 10.3389/fphar.2020.00408; Lucanus AJ, 2018, ONCOGENE, V37, P833, DOI 10.1038/onc.2017.406; Ma HT, 2014, MOL ONCOL, V8, P1404, DOI 10.1016/j.molonc.2014.05.007; Miki H, 2005, TRENDS CELL BIOL, V15, P467, DOI 10.1016/j.tcb.2005.07.006; O'Connell MJ, 2014, J CLIN ONCOL, V32, P1927, DOI 10.1200/JCO.2013.53.7753; Rath O, 2012, NAT REV CANCER, V12, P527, DOI 10.1038/nrc3310; Rocha CRR, 2018, CLINICS, V73, DOI 10.6061/clinics/2018/e478s; Stavoe AKH, 2016, DEV CELL, V38, P171, DOI 10.1016/j.devcel.2016.06.012; Van Cutsem E, 2014, ANN ONCOL, V25, P1, DOI 10.1093/annonc/mdu260; Venere M, 2015, SCI TRANSL MED, V7, DOI 10.1126/scitranslmed.aac6762; Verwaal VJ, 2003, J CLIN ONCOL, V21, P3737, DOI 10.1200/JCO.2003.04.187; Wang X, 2016, CANCER RES, V76, P7277, DOI 10.1158/0008-5472.CAN-16-2100; Wang YN, 2016, MOL CELL, V63, P34, DOI 10.1016/j.molcel.2016.05.027; Wojcik EJ, 2013, GENE, V531, P133, DOI 10.1016/j.gene.2013.08.004; Xiong M, 2019, AGING-US, V11, P11905, DOI 10.18632/aging.102505; Zou JX, 2014, MOL CANCER RES, V12, P539, DOI 10.1158/1541-7786.MCR-13-0459	46	2	2	0	2	IVYSPRING INT PUBL	LAKE HAVEN	PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA	1837-9664			J CANCER	J. Cancer		2021	12	12					3741	3753		10.7150/jca.52103			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	RZ4TW	WOS:000648591100030	33995648	gold, Green Published			2022-04-25	
J	See, CS; Kitagawa, M; Liao, PJ; Lee, KH; Wong, J; Lee, SH; Dymock, BW				See, Cheng Shang; Kitagawa, Mayumi; Liao, Pei-Ju; Lee, Kyung Hee; Wong, Jasmine; Lee, Sang Hyun; Dymock, Brian W.			Discovery of the cancer cell selective dual acting anti-cancer agent (Z)-2-(1H-indol-3-yl)-3-(isoquinolin-5-yl)acrylonitrile (A131)	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY			English	Article						Antitumor; Antimitotic; Antiproliferative; Tumor-selective	IN-VITRO; PAPROTRAIN; INHIBITORS; AUTOPHAGY; MODELS; VIVO; LC3	Selective targeting of cancer cells over normal cells is a key objective of targeted therapy. However few approaches achieve true mechanistic selectivity resulting in debilitating side effects and dose limitation. In this work we describe the discovery of A131 (4a), a new agent with an unprecedented dual mechanism of action targeting both mitosis and autophagy. Compound 4a was first identified in a phenotypic screen in which HeLa cells treated with 4a manifested mitotic arrest along with formation of multiple vesicles. Further investigations showed that 4a causes an increase in mitotic marker pH3 and autophagy marker LC3. Importantly 4a induces cell death in cancer cells while sparing normal cells which regrow after 4a is removed. Dual activities against pH3 and LC3 markers are required for cancer cell selectivity. An extensive SAR investigation confirmed 4a as the optimal dual inhibitor with potency against a panel of 30 cancer cell lines (average antiproliferative GI(50) 1.5 mu M). In a mouse model of paclitaxel-resistant colon cancer, 4a showed 74% tumor growth inhibition when administered at a dose of 20 mg/kg IP twice a day. (C) 2018 Elsevier Masson SAS. All rights reserved.	[See, Cheng Shang; Dymock, Brian W.] Natl Univ Singapore, Dept Pharm, Singapore 117543, Singapore; [Kitagawa, Mayumi; Liao, Pei-Ju; Lee, Kyung Hee; Wong, Jasmine; Lee, Sang Hyun] Duke NUS Med Sch, Program Canc & Stem Cell Biol, Singapore 169857, Singapore		Dymock, BW (corresponding author), Natl Univ Singapore, Dept Pharm, Singapore 117543, Singapore.	bwdnus@gmail.com		Dymock, Brian/0000-0002-2374-5756	National University of Singapore (Faculty of Science start-up grant)National University of Singapore [R-148-000-169-133]; NMRC CBRGNational Medical Research Council, Singapore [NMRC/CBRG/0091/2015]; Duke-NUS Medical School [NUS/RECA(PILOT/2013/0006)];  [NRF-RF2010-02]	We gratefully acknowledge Dr Yang Shili and Professor Paul Ho for providing the RLM and rat PK data, and Ms Sheela David Packiaraj and Associate Professor Ho Han Kiat for providing the TAMH, AC10 and AMES data. This research was funded by generous grants from the National University of Singapore (Faculty of Science start-up grant R-148-000-169-133 to B.D.), the National Research Fellow (S.H.L.; NRF-RF2010-02) program, NMRC CBRG (S.H.L.; NMRC/CBRG/0091/2015) and the Duke-NUS Medical School [NUS/RECA(PILOT/2013/0006)].	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J	Yao, YZ; Hu, H; Yang, Y; Zhou, GQ; Shang, ZF; Yang, XD; Sun, K; Zhan, SH; Yu, ZY; Li, PY; Pan, GF; Sun, L; Zhu, XG; He, SB				Yao, Yizhou; Hu, Hao; Yang, Yong; Zhou, Guoqiang; Shang, Zengfu; Yang, Xiaodong; Sun, Kang; Zhan, Shenghua; Yu, Zhengyuan; Li, Peiyao; Pan, Guofeng; Sun, Liang; Zhu, Xinguo; He, Songbing			Downregulation of Enhancer of Zeste Homolog 2 (EZH2) Is Essential for the Induction of Autophagy and Apoptosis in Colorectal Cancer Cells	GENES			English	Article						EZH2; shRNA; DZNep; autophagy; apoptosis; colorectal cancer	HISTONE METHYLTRANSFERASE; EXPRESSION; PROLIFERATION; CARCINOMA; SENSITIVITY; INHIBITION; PATHWAYS; POLYCOMB; PROSTATE; MARKER	Increasing evidence indicates that elevated expression of enhancer of zeste homolog 2 gene (EZH2) in many human malignant tumors acts a significant role in the oncogenic process. However, the underlying molecular mechanism is still unclarified. It is evident that apoptosis and autophagy of tumor cells is crucial for the tumorigenesis and progression of cancer, however, the exact role of EZH2 plays in apoptosis and autophagy has not been fully elucidated in colorectal cancer (CRC). Our previous study found that the expression level of EZH2 was higher in CRC tumor tissues than in the paired normal tissues using immunohistochemical analysis. We also recently found that the autophagy-related gene-related protein Ambra1 plays an important role in the autophagy pathway in CRC cells. In this study, mRNA and protein expression of EZH2 in four CRC cell lines were tested at first and RKO and HCT116 cells showed the highest levels among them. Here we transfected with EZH2-shRNA, or added DZNep (an EZH2 inhibitor) to RKO and HCT116 cells in order to detect the effect of EZH2 on autophagy via determining the change of the protein expression of LC3 and Ambra1. The outcome indicated an obvious decrease of autophagy level in cells transfected with EZH2-shRNA or DZNep. We also found the apoptotic rate of cells was elevated significantly after downregulation of EZH2. In addition, compared to control group, CRC cells transfected with EZH2-shRNA or added DZNep revealed a significantly increased G1 cell cycle rate and an obvious decrease in the G2 cell cycle rate. Further analysis showed that knockdown of EZH2 induced cell-cycle arrest in CRC cells. Meanwhile, downregulation of EZH2 in CRC cells induces autophagy and apoptosis. Taken together, our results suggest that EZH2 plays a critical role in autophagy and apoptosis in the progression of CRC, which potentially facilitates the development of an ideal strategy for combating colorectal cancer.	[Yao, Yizhou; Hu, Hao; Yang, Yong; Pan, Guofeng; Sun, Liang; Zhu, Xinguo; He, Songbing] Soochow Univ, Dept Gen Surg, Affiliated Hosp 1, Suzhou 215006, Peoples R China; [Zhou, Guoqiang] Changshu 2 Hosp, Dept Gastrointestinal Surg, Suzhou 215500, Peoples R China; [Shang, Zengfu] Soochow Univ, Dept Radiat Med, Coll Med, Suzhou 215006, Peoples R China; [Yang, Xiaodong] Soochow Univ, Dept Gen Surg, Affiliated Hosp 2, Suzhou 215006, Peoples R China; [Sun, Kang] Jiangsu Univ, Dept Gen Surg, Affiliated Hosp, Zhenjiang 212001, Peoples R China; [Zhan, Shenghua] Soochow Univ, Dept Pathol, Affiliated Hosp 1, Suzhou 215006, Peoples R China; [Yu, Zhengyuan] Soochow Univ, Dept Oncol, Affiliated Hosp 1, Suzhou 215006, Peoples R China; [Li, Peiyao] Chinese Peoples Liberat Army Gen Hosp, Med Engn & Maintenance Ctr, Beijing 100853, Peoples R China		He, SB (corresponding author), Soochow Univ, Dept Gen Surg, Affiliated Hosp 1, Suzhou 215006, Peoples R China.	yaoyizhou2014@163.com; lidechun1955@163.com; magicy@126.com; chowgq@sina.com; zengfu.shang@suda.edu.cn; wjyxd@163.com; doctorsunkang@126.com; captain_hsb@163.com; strongeryy1985@163.com; li_peiyao@163.com; 1030705022@suda.edu.cn; 1130705026@suda.edu.cn; zxg45@hotmail.com; hesongbing1979@suda.edu.cn	yao, yizhou/ABE-8728-2020; Sun, Liang/AAY-4646-2021	Shang, Zeng-Fu/0000-0002-2396-1416; Yao, Yizhou/0000-0001-7976-1133; YU, ZHENGYUAN/0000-0002-6148-1907; Sun, Liang/0000-0002-2721-1866	Project of Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672348]; Six Major Talent Peak Project of Jiangsu Province of China [2015-WSW-014]; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry of ChinaScientific Research Foundation for the Returned Overseas Chinese ScholarsMinistry of Education, China; National Science Foundation of Jiangsu Province, China [BK2016255]; Project of Medical Science and Technology Development Foundation of Jiangsu Province of China [YG201406]; Science and Technology Research Project of Changshu City of China [CS201504]	The present study was supported by Project of Nature Science Foundation of China (81672348), the Six Major Talent Peak Project of Jiangsu Province of China (2015-WSW-014), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry of China (fiftieth batch, 2015), the National Science Foundation of Jiangsu Province, China (BK2016255), Project of Medical Science and Technology Development Foundation of Jiangsu Province of China (YG201406) and Science and Technology Research Project of Changshu City of China (CS201504).	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J	Cosper, PF; Leinwand, LA				Cosper, Pippa F.; Leinwand, Leslie A.			Cancer Causes Cardiac Atrophy and Autophagy in a Sexually Dimorphic Manner	CANCER RESEARCH			English	Article							UBIQUITIN-PROTEASOME PATHWAY; SKELETAL-MUSCLE; MYOFIBRILLAR PROTEINS; MYOCARDIAL STIFFNESS; CONTRACTILE FUNCTION; HEMODYNAMIC STRESS; CACHEXIA; HEART; RAT; DEGRADATION	Approximately one-third of cancer deaths are caused by cachexia, a severe form of skeletal muscle and adipose tissue wasting that affects men more than women. The heart also undergoes atrophy in cancer patients, but the mechanisms and the basis for apparent sex differences are unclear. In a mouse colon-adenocarcinoma model, cancer causes a loss of cardiac mass due to a decrease in cardiac myocyte size that is associated with reduced levels of all sarcomeric proteins. Unlike skeletal muscle cachexia, atrophic hearts do not upregulate the ubiquitin-proteasome system or its activity but increase autophagy. Thus, cancer causes cardiac atrophy by a mechanism distinct from that in skeletal muscle. Male tumor-bearing mice have a more severe phenotype than females, including greater cardiac mass loss and mortality, a more robust pro-inflammatory response to the tumor, and greater cardiac autophagy. In females, estrogen protects against cancer-induced cardiac atrophy and body weight loss by signaling through its receptor. Sex differences in cardiac atrophy need to be considered during the treatment of patients suffering from chemotherapy-induced cardiomyopathy to prevent exacerbation of cardiac dysfunction. Cancer Res; 71( 5); 1710-20. (C)2010 AACR.	[Cosper, Pippa F.; Leinwand, Leslie A.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA		Leinwand, LA (corresponding author), Room A417,UCB 354, Boulder, CO 80309 USA.	Leslie.Leinwand@colorado.edu		Cosper, Pippa/0000-0003-3362-5587; LEINWAND, LESLIE/0000-0003-1470-4810	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [2RO1HL050560]; American Heart AssociationAmerican Heart Association [0810037Z]; National Heart Lung and Blood InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [3T32GM008497-S1]; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL050560] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [T32GM008497] Funding Source: NIH RePORTER	This work was supported by an NIH grant (2RO1HL050560 to L.A. Leinwand), a predoctoral fellowship from the American Heart Association (0810037Z to P.F. Cosper), and a grant from the National Heart Lung and Blood Institute (3T32GM008497-S1 to P.F. Cosper).	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MAR 1	2011	71	5					1710	1720		10.1158/0008-5472.CAN-10-3145			11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	728AH	WOS:000287845300022	21163868	Green Accepted, Bronze			2022-04-25	
J	Vignot, S; Lefebvre, C; Frampton, GM; Meurice, G; Yelensky, R; Palmer, G; Capron, F; Lazar, V; Hannoun, L; Miller, VA; Andre, F; Stephens, PJ; Soria, JC; Spano, JP				Vignot, Stephane; Lefebvre, Celine; Frampton, Garrett M.; Meurice, Guillaume; Yelensky, Roman; Palmer, Gary; Capron, Frederique; Lazar, Vladimir; Hannoun, Laurent; Miller, Vincent A.; Andre, Fabrice; Stephens, Philip J.; Soria, Jean-Charles; Spano, Jean-Philippe			Comparative analysis of primary tumour and matched metastases in colorectal cancer patients: Evaluation of concordance between genomic and transcriptional profiles	EUROPEAN JOURNAL OF CANCER			English	Article						Colorectal cancer; Primary tumour; Metastasis; Discrepancies; Recurrent mutations	INTRATUMOR HETEROGENEITY; COLON; ADRENALINE; MUTATIONS; THERAPY	Purpose: Focal and temporal tumour heterogeneity can represent a major challenge for biology-guided therapies. This study proposes to investigative molecular discrepancies between primary colorectal cancer (CRC) samples and matched metastases. Experimental design: Surgical samples from primary and matched metastatic tissues from 13 CRC patients along with their adjacent normal tissue were evaluated. A mutational analysis was performed using a targeted Next Generation Sequencing assay (Foundation Medicine) with a focus on known recurrent somatic mutations as surrogate of key oncogenic events. Gene expression analysis was also performed to investigate transcriptional discrepancies. Results: Among the 26 samples, 191 mutations were identified including mutations in APC (13 pts), TP53 (11 pts), and KRAS (7 pts). Global concordance rate for mutations was 78% between primary and metastatic tumours and raised to 90% for 12 known recurrent mutations in CRC. Differential gene expression analysis revealed a low number of significantly variant transcripts between primary and metastatic tumours once the tissue effect was taken into account. Only two pathways (ST_ADRENERGIC, PID_REELINPATHWAY) were differentially up-regulated in metastases among 17 variant pathways. A common profile in primary and metastatic tumours revealed conserved pathways mostly involved in cell cycle regulation. Only two pathways were significantly down regulated compared to normal control, including regulation of autophagy (KEGG_ REGULATION_OF_AUTOPHAGY). Conclusion: These results suggest that profiles of primary tumour can identify key alterations present in matched CRC metastases at first metastatic progression. Gene expression analysis identified mainly conserved pathways between primary tumour and matched liver metastases. (C) 2015 Elsevier Ltd. All rights reserved.	[Vignot, Stephane] Hop Chartres, Oncol Hematol, Chartres, France; [Vignot, Stephane; Lefebvre, Celine; Andre, Fabrice; Soria, Jean-Charles] Inst Gustave Roussy, INSERM, U981, F-94805 Villejuif Grand Paris, France; [Frampton, Garrett M.; Yelensky, Roman; Palmer, Gary; Miller, Vincent A.; Stephens, Philip J.] Fdn Med, Cambridge, MA USA; [Meurice, Guillaume; Lazar, Vladimir] Inst Gustave Roussy, Unite Genom Fonct, F-94805 Villejuif Grand Paris, France; [Capron, Frederique; Hannoun, Laurent; Spano, Jean-Philippe] Grp Hosp Pitie Salpetriere, F-75634 Paris, France		Soria, JC (corresponding author), Inst Gustave Roussy, INSERM, U981, 114 Rue Edouard Vaillant, F-94805 Villejuif Grand Paris, France.	jean-charles.soria@gustaveroussy.fr	Lazar, Vladimir/AAV-2087-2020; ANDRE, Fabrice/AAL-2683-2020; Kessenbrock, Kai/B-6936-2011; Soria, Jean-Charles/F-3619-2014; Lazar, Vladimir/AAQ-2086-2020; Lefebvre, Celine/E-6290-2013	ANDRE, Fabrice/0000-0001-5795-8357; 			Beroukhim R, 2010, NATURE, V463, P899, DOI 10.1038/nature08822; Cho YY, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0057172; Forbes SA, 2011, NUCLEIC ACIDS RES, V39, pD945, DOI 10.1093/nar/gkq929; Gentleman RC, 2004, GENOME BIOL, V5, DOI 10.1186/gb-2004-5-10-r80; Gerlinger M, 2010, BRIT J CANCER, V103, P1139, DOI 10.1038/sj.bjc.6605912; Gerlinger M, 2012, NEW ENGL J MED, V366, P883, DOI 10.1056/NEJMoa1113205; Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013; HOURI JJ, 1993, BIOCHEM BIOPH RES CO, V197, P805, DOI 10.1006/bbrc.1993.2550; Jossin Yves, 2011, Small GTPases, V2, P322; Kim MY, 2009, CELL, V139, P1315, DOI 10.1016/j.cell.2009.11.025; Lee S, 2014, PLOS ONE, V5; Li H, 2009, BIOINFORMATICS, V25, P1754, DOI 10.1093/bioinformatics/btp324; McKenna A, 2010, GENOME RES, V20, P1297, DOI 10.1101/gr.107524.110; Melhem-Bertrandt A, 2011, J CLIN ONCOL, V29, P2645, DOI 10.1200/JCO.2010.33.4441; Misale S, 2012, NATURE, V486, P532, DOI 10.1038/nature11156; Muzny DM, 2012, NATURE, V487, P330, DOI 10.1038/nature11252; Norton L, 2006, NAT MED, V12, P875, DOI 10.1038/nm0806-875; Powe DG, 2010, ONCOTARGET, V1, P628, DOI 10.18632/oncotarget.197; Sato N, 2006, GASTROENTEROLOGY, V130, P548, DOI 10.1053/j.gastro.2005.11.008; Smyth G. 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J. Cancer	MAY	2015	51	7					791	799		10.1016/j.ejca.2015.02.012			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CG1LT	WOS:000353034800001	25797355				2022-04-25	
J	Zhang, DY; Reyes, RM; Osta, E; Kari, S; Gupta, HB; Padron, AS; Kornepati, AVR; Kancharla, A; Sun, XJ; Deng, YL; Wu, BG; Vadlamudi, R; Li, R; Svatek, RS; Curiel, TJ				Zhang, Deyi; Reyes, Ryan M.; Osta, Erica; Kari, Suresh; Gupta, Harshita B.; Padron, Alvaro S.; Kornepati, Anand V. R.; Kancharla, Aravind; Sun, Xiujie; Deng, Yilun; Wu, Bogang; Vadlamudi, Ratna; Li, Rong; Svatek, Robert S.; Curiel, Tyler J.			Bladder cancer cell-intrinsic PD-L1 signals promote mTOR and autophagy activation that can be inhibited to improve cytotoxic chemotherapy	CANCER MEDICINE			English	Article						autophagy; bladder cancer; chemotherapy; mTOR; PD&#8208; L1		Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate immunopathologic effects in breast, colon, and ovarian cancers and in melanomas, but bladder cancer (BC) effects are unreported. We show here that BC cell-intrinsic PD-L1 signals in mouse MB49 and human RT4, UM-UC3, and UM-UC-14 BC cells regulate important pathologic pathways and processes, including effects not reported in other cancers. alpha-PD-L1 antibodies reduced BC cell proliferation in vitro, demonstrating direct signaling effects. BC cell-intrinsic PD-L1 promoted mammalian target of rapamycin complex 1 (mTORC1) signals in vitro and augmented in vivo immune-independent cell growth and metastatic cancer spread, similar to effects we reported in melanoma and ovarian cancer. BC cell-intrinsic PD-L1 signals also promoted basal and stress-induced autophagy, whereas these signals inhibited autophagy in melanoma and ovarian cancer cells. BC cell-intrinsic PD-L1 also mediated chemotherapy resistance to the commonly used BC chemotherapy agents cis-platinum and gemcitabine and to the mTORC1 inhibitor, rapamycin. Thus, BC cell-intrinsic PD-L1 signals regulate important virulence and treatment resistance pathways that suggest novel, actionable treatment targets meriting additional studies. As a proof-of-concept, we showed that the autophagy inhibitor chloroquine improved cis-platinum treatment efficacy in vivo, with greater efficacy in PD-L1 null versus PD-L1-replete BC.	[Zhang, Deyi; Kari, Suresh; Gupta, Harshita B.; Padron, Alvaro S.; Kancharla, Aravind; Sun, Xiujie; Deng, Yilun; Curiel, Tyler J.] Univ Texas Hlth, Dept Med, San Antonio, TX USA; [Reyes, Ryan M.; Osta, Erica; Kornepati, Anand V. R.; Curiel, Tyler J.] Univ Texas Hlth, Grad Sch Biomed Sci, San Antonio, TX USA; [Reyes, Ryan M.; Osta, Erica; Kornepati, Anand V. R.; Curiel, Tyler J.] Univ Texas Hlth, Dept Microbiol Immunol & Mol Genet, San Antonio, TX USA; [Reyes, Ryan M.; Vadlamudi, Ratna; Li, Rong; Svatek, Robert S.; Curiel, Tyler J.] Univ Texas Hlth, Mays Canc Ctr, San Antonio, TX USA; [Wu, Bogang; Li, Rong] Univ Texas Hlth, Dept Mol Med, San Antonio, TX USA; [Vadlamudi, Ratna] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA; [Svatek, Robert S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA; [Zhang, Deyi] NIH, Bldg 10, Bethesda, MD 20892 USA; [Sun, Xiujie; Wu, Bogang; Li, Rong] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Med, Washington, DC 20052 USA		Curiel, TJ (corresponding author), Univ Texas Hlth San Antonio, Dept Med, STRF MC 8252,8403 Floyd Curl Dr, San Antonio, TX 78229 USA.	curielt@uthscsa.edu	Reyes, Ryan/AAZ-9671-2021; Wu, Bogang/O-2441-2018	Reyes, Ryan/0000-0002-9562-5809; Wu, Bogang/0000-0003-1654-198X; Kancharla, Aravind/0000-0001-9095-7735	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [T32GM113896, F30CA239390]; NIH/NCATSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [TL1 TR002647]; NIAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [T32 AG 021890]; CPRIT Research Training Award [RP170345]; Roger L. And Laura D. Zeller Charitable Foundation Chair in Urologic Cancer [CDMRP CA170270/P1P2]; CDMRPUnited States Department of Defense [CA054174,, CA205965]; Owens Foundation; Skinner endowment; Barker endowment; Clayton Medical Research Foundation;  [8KL2 TR000118];  [K23];  [P30 CA054174]	R. Reyes (NIH T32GM113896, NIH/NCATS TL1 TR002647, NIA T32 AG 021890), A. Kornepati (NIH F30CA239390), Y. Deng (CPRIT Research Training Award RP170345), R. Svatek (8KL2 TR000118, K23, P30 CA054174, Roger L. And Laura D. Zeller Charitable Foundation Chair in Urologic Cancer, CDMRP CA170270/P1P2), T. Curiel (CA054174, CA205965, CDMRP, The Owens Foundation, The Skinner endowment, The Barker endowment, Clayton Medical Research Foundation).	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MAR	2021	10	6					2137	2152		10.1002/cam4.3739		FEB 2021	16	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	QW5WQ	WOS:000621118800001	33626233	gold, Green Published			2022-04-25	
J	De Palma, C; Perrotta, C				De Palma, Clara; Perrotta, Cristiana			Ceramide as a target of chemotherapy: its role in apoptosis and autophagy	CLINICAL LIPIDOLOGY			English	Review						apoptosis; autophagy; ceramide; chemotherapy	INDUCED CELL-DEATH; ACTIVATED PROTEIN-KINASE; COLON-CANCER CELLS; ACID-SPHINGOMYELINASE; NEUTRAL SPHINGOMYELINASE; GLUCOSYLCERAMIDE SYNTHASE; NANOLIPOSOMAL CERAMIDE; SPHINGOSINE KINASE-1; MULTIDRUG-RESISTANCE; STRESS-RESPONSE	Conventional chemotherapy is the elective and most effective strategy for tumor treatment. Several studies have demonstrated that a mechanism through which most chemotherapeutic agents kill tumor cells is to trigger their death through the generation of ceramide via the activation of enzymes responsible either for its de novo synthesis or for the degradation of sphingomyelin. Ceramide-induced cell death has been widely investigated, with a particular focus on apoptosis. Moreover, recently, the role of ceramide in the induction of autophagy has come to light, opening new questions on how sphingolipid messengers can act in these different but linked pathways. Cellular stress can indeed promote autophagy and apoptosis in multiple ways, including their induction sequentially, simultaneously, or in a mutually exclusive manner. This review presents some of the recent advances regarding the role of ceramide in the induction of apoptosis/autophagy, focusing on its modulation as a strategy for an effective cancer therapy.	[De Palma, Clara; Perrotta, Cristiana] Univ Milan, Univ Hosp Luigi Sacco, Dept Clin Sci, Clin Pharmacol Unit, I-20157 Milan, Italy		Perrotta, C (corresponding author), Univ Milan, Univ Hosp Luigi Sacco, Dept Clin Sci, Clin Pharmacol Unit, I-20157 Milan, Italy.	cristiana.perrotta@unimi.it	PERROTTA, CRISTIANA/A-9179-2010; Perrotta, Cristiana/I-2835-2016; De Palma, Clara/M-9842-2019	Perrotta, Cristiana/0000-0001-6680-4536; De Palma, Clara/0000-0003-0365-7414	Italian Association of Cancer Research (AIRC)Fondazione AIRC per la ricerca sul cancro	This work was supported by research grants from the Italian Association of Cancer Research (AIRC). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.	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Lipidol.	FEB	2012	7	1					111	119		10.2217/CLP.11.71			9	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	896DV	WOS:000300546500014					2022-04-25	
J	Liu, C; Wang, JN; Yang, Y; Liu, XT; Zhu, YB; Zou, JJ; Peng, SS; Le, TH; Chen, Y; Zhao, SL; He, BS; Mi, QY; Zhang, X; Du, QM				Liu, Chao; Wang, Jianing; Yang, Yan; Liu, Xiuting; Zhu, Yubing; Zou, Jianjun; Peng, Sishi; Le, Thi Ha; Chen, Yu; Zhao, Shuli; He, Bangshun; Mi, Qiongyu; Zhang, Xu; Du, Qianming			Ginsenoside Rd ameliorates colitis by inducing p62-driven mitophagy-mediated NLRP3 inflammasome inactivation in mice	BIOCHEMICAL PHARMACOLOGY			English	Article						Ulcerative colitis; Inflammation; Ginsenoside Rd; NLRP3 Inflammasome; P62	CROHNS-DISEASE; BOWEL-DISEASE; IFN-GAMMA; AUTOPHAGY; ACTIVATION; MOUSE; PHOSPHORYLATION; PANCREATITIS; IMMUNITY; INNATE	Previous studies reported that Ginsenoside Rd (Rd) had anti-inflammatory and anti-cancer effects. However, the molecular mechanism underlying the inhibition effect of Rd on colitis in mice hasn't been clarified clearly. Here, in our study, we detected the effects of Rd on dextran sulfate sodium (DSS)-induced murine colitis, and found that oral administration of Rd dose-dependently alleviated DSS-induced body weight loss, colon length shortening and colonic pathological damage with lower myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities and higher glutathione level. In addition, the production of pro-inflammatory cytokines (IL-1 beta, TNF-a and IL-6) in both serum and colonic tissues were significantly down-regulated by Rd administration. The activation of NLRP3 inflammasome was also suppressed in Rd-treated group, resulting in reduced caspase-1 production and IL-1 beta secretion. In vitro, Rd remarkably inhibited NLRP3 inflammasome activation which was mostly dependent on the mitochondrial translocation of p62 and mitophagy. Importantly, Rd-driven inhibition of the NLRP3 inflammasome was significantly blocked by various autophagy inhibitors. Furthermore, upregulation of AMPK/ULK1 signaling pathway accounted for Rd-induced autophagy, which was also seen in vivo. In conclusion, our results demonstrated the function of Rd on the inhibition NLRP3 inflammasome and its potential application for the treatment of NLRP3-associated diseases.	[Liu, Chao; Zhu, Yubing; Zou, Jianjun; Le, Thi Ha; Chen, Yu] Nanjing Med Univ, Nanjing Hosp 1, Dept Pharm, Nanjing 210006, Jiangsu, Peoples R China; [Liu, Chao; Liu, Xiuting; Zhu, Yubing; Zou, Jianjun; Peng, Sishi; Le, Thi Ha; Chen, Yu; Du, Qianming] China Pharmaceut Univ, Sch Basic Med & Clin Pharm, Dept Clin Pharm, Nanjing 210009, Jiangsu, Peoples R China; [Wang, Jianing] China Pharmaceut Univ, Jiangsu Ctr Drug Screening, Neurobiol Lab, Nanjing 210009, Jiangsu, Peoples R China; [Yang, Yan] Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Dept Pharm, 82 Qing Long St, Chengdu 610031, Sichuan, Peoples R China; [Yang, Yan] Southwest Jiaotong Univ, Affiliated Hosp, 82 Qing Long St, Chengdu 610031, Sichuan, Peoples R China; [Peng, Sishi; Zhao, Shuli; He, Bangshun; Mi, Qiongyu; Du, Qianming] Nanjing Med Univ, Nanjing Hosp 1, Gen Clin Res Ctr, Nanjing 210006, Jiangsu, Peoples R China; [Zhang, Xu] First Peoples Hosp Chengdu, Dept Med, 18 Wanxiang East Rd, Chengdu 610041, Sichuan, Peoples R China; [Zhang, Xu] Chengdu Med Coll, Affiliated Hosp, 18 Wanxiang East Rd, Chengdu 610041, Sichuan, Peoples R China		Zhang, X; Du, QM (corresponding author), First Peoples Hosp Chengdu, Dept Med, 18 Wanxiang East Rd, Chengdu 610041, Sichuan, Peoples R China.; Zhang, X; Du, QM (corresponding author), Chengdu Med Coll, Affiliated Hosp, 18 Wanxiang East Rd, Chengdu 610041, Sichuan, Peoples R China.	Jason151X7@stu.cpu.edu.cn; duqianming@stu.cpu.edu.cn		, Qianming Du/0000-0002-1092-2899	Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81702833]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20170137, BK20170140]; Sichuan Science and Technology Program [2018JY0204]; Natural Science Foundation of Chengdu Medical College [CYZ17-13]; Science and Technology Development Fund Project of Nanjing Medical University [2016NJMUZD041, 2016NJMUZD043]	This work was supported by the Natural Science Foundation of China (No. 81702833), the Natural Science Foundation of Jiangsu Province (No. BK20170137 and No. BK20170140), Sichuan Science and Technology Program (No. 2018JY0204), Natural Science Foundation of Chengdu Medical College (No. CYZ17-13) and the Science and Technology Development Fund Project of Nanjing Medical University (No. 2016NJMUZD041 and No. 2016NJMUZD043).	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Pharmacol.	SEP	2018	155						366	379		10.1016/j.bcp.2018.07.010			14	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	GU5JZ	WOS:000445323100035	30012462				2022-04-25	
J	Sroda-Pomianek, K; Michalak, K; Swiatek, P; Pola, A; Palko-Labuz, A; Wesolowska, O				Sroda-Pomianek, Kamila; Michalak, Krystyna; Swiatek, Piotr; Pola, Andrzej; Palko-Labuz, Anna; Wesolowska, Olga			Increased lipid peroxidation, apoptosis and selective cytotoxicity in colon cancer cell line LoVo and its doxorubicin-resistant subline LoVo/Dx in the presence of newly synthesized phenothiazine derivatives	BIOMEDICINE & PHARMACOTHERAPY			English	Article						Phenothiazine derivatives; Cytotoxicity; Apoptosis; Lipid peroxidation; Reactive oxygen species (ROS); Doxorubicin-Resistant cancer cells	MULTIDRUG-RESISTANCE; OXIDATIVE STRESS; P-GLYCOPROTEIN; COLLATERAL SENSITIVITY; COLORECTAL-CANCER; INDUCE APOPTOSIS; REVERSAL; CHLORPROMAZINE; ANTIOXIDANT; INHIBITION	Cancer cells often develop the resistance to pro-apoptotic signaling that makes them invulnerable to conventional treatment. Therapeutic strategies that make cancer cells enter the path of apoptosis are desirable due to the avoidance of inflammatory reaction that usually accompanies necrosis. In the present study phenothiazines (fluphenazine and four recently synthesized derivatives) were investigated in order to identify compounds with a potent anticancer activity. Since phenothiazines are known as multidrug resistance modulators the sensitive human colorectal adenocarcinoma cell line (LoVo) and its doxorubicin-resistant, ABCB1 overexpressing, subline (LoVo/Dx) have been employed as a model system. In studied cancer cells cytotoxic effect of the phenothiazine derivatives was accompanied by apoptosis and autophagy induction as well as by the increase of cellular lipid peroxidation and intracellular reactive oxygen species generation. Molecular modelling revealed that reactivity of phenothazines (manifested by their low energy gap) but not lipophilicity was positively correlated with their anticancer potency, pro-oxidant properties and apoptosis induction ability. Additionally, some of the studied compounds turned out to be more potent cytotoxic and pro-apoptotic agents in doxorubicin-resistant (LoVo/Dx) cells than in sensitive ones (LoVo). The hypothesis was assumed that studied phenothiazine derivatives induced apoptotic cell death by increasing the production of reactive oxygen species.	[Sroda-Pomianek, Kamila; Michalak, Krystyna; Pola, Andrzej; Palko-Labuz, Anna; Wesolowska, Olga] Wroclaw Med Univ, Dept Biophys, Ul Chalubinskiego 10, PL-50368 Wroclaw, Poland; [Swiatek, Piotr] Wroclaw Med Univ, Dept Drug Chem, Ul Borowska 211, PL-50556 Wroclaw, Poland		Sroda-Pomianek, K (corresponding author), Wroclaw Med Univ, Dept Biophys, Ul Chalubinskiego 10, PL-50368 Wroclaw, Poland.	kamila.sroda-pomianek@umed.wroc.pl	Świątek, Piotr/K-7423-2019	Wesolowska, Olga/0000-0003-1659-3288; Michalak, Krystyna/0000-0002-4018-8867; Pola, Andrzej/0000-0002-4110-299X; Swiatek, Piotr/0000-0003-4613-025X; Sroda-Pomianek, Kamila/0000-0003-3454-5044; Palko-Labuz, Anna/0000-0002-4246-5717	Polish Ministry of Science and Higher EducationMinistry of Science and Higher Education, Poland	This work was supported by Polish Ministry of Science and Higher Education (funds for Wroclaw Medical University).	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J	Weh, KM; Clarke, J; Kresty, LA				Weh, Katherine M.; Clarke, Jennifer; Kresty, Laura A.			Cranberries and Cancer: An Update of Preclinical Studies Evaluating the Cancer Inhibitory Potential of Cranberry and Cranberry Derived Constituents	ANTIOXIDANTS			English	Review						cranberry; cancer; proanthocyanidin; quercetin; ursolic acid	CELL-CYCLE ARREST; FIMBRIATED ESCHERICHIA-COLI; VACCINIUM-MACROCARPON; DOUBLE-BLIND; PROANTHOCYANIDINS INHIBIT; ANTIADHESION ACTIVITY; CYTOTOXIC PROPERTIES; ANTIOXIDANT STATUS; GUT MICROBIOTA; BREAST-CANCER	Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques, whereas in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy in high risk cohorts should be considered.	[Weh, Katherine M.; Kresty, Laura A.] Med Coll Wisconsin, Div Hematol & Oncol, Dept Med, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA; [Clarke, Jennifer] Univ Nebraska, Dept Food Sci & Technol, 256 Food Innovat Complex, Lincoln, NE 68588 USA; [Clarke, Jennifer] Univ Nebraska, Dept Stat, Lincoln, NE 68583 USA; [Clarke, Jennifer] Univ Nebraska, Quantitat Life Sci Initiat, Lincoln, NE 68583 USA		Kresty, LA (corresponding author), Med Coll Wisconsin, Div Hematol & Oncol, Dept Med, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.	kweh@mcw.edu; jclarke3@unl.edu; lkresty@mcw.edu		Weh, Katherine/0000-0002-7745-5391; Kresty, Laura/0000-0002-4745-0522; Clarke, Jennifer/0000-0002-2723-7249	NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA158319] Funding Source: NIH RePORTER; NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01 CA158319] Funding Source: Medline		Agbarya A, 2014, SAGE OPEN MED, V2, DOI 10.1177/2050312114546924; 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Xiao X, 2015, FOOD CHEM, V167, P438, DOI 10.1016/j.foodchem.2014.07.006; Zhang K, 2004, J AGR FOOD CHEM, V52, P222, DOI 10.1021/jf035073r	80	30	30	4	30	MDPI	BASEL	ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND	2076-3921			ANTIOXIDANTS-BASEL	Antioxidants	SEP	2016	5	3							27	10.3390/antiox5030027			20	Biochemistry & Molecular Biology; Chemistry, Medicinal; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Food Science & Technology	DU9AT	WOS:000382509300007	27548236	Green Published, gold			2022-04-25	
J	da Silva-Camargo, CCV; Baldin, RKS; Polli, NLC; Agostinho, AP; Olandosk, M; de Noronha, L; Sotomaior, VS				Veloso da Silva-Camargo, Claudia Caroline; Svoboda Baldin, Rosimeri Kuhl; Costacurta Polli, Nayanne Louise; Agostinho, Amanda Pereira; Olandosk, Marcia; de Noronha, Lucia; Sotomaior, Vanessa Santos			Parkin protein expression and its impact on survival of patients with advanced colorectal cancer	CANCER BIOLOGY & MEDICINE			English	Article						Parkin; PARK2; advanced colorectal cancer; survival	RECESSIVE JUVENILE PARKINSONISM; MITOPHAGY; MITOCHONDRIA; GENE; CARCINOMA; LIGASE; PROLIFERATION; ACTIVATION; PROGNOSIS; AUTOPHAGY	Objective: Features of colorectal cancer such as natural history, molecular, chromosomal, and epigenetic alterations have been well described. However, there is still a lack of accurate prognostic markers, which is evident by the lower overall survival rates of patients with advanced cancer. Although alterations in parkin protein expression have been described in colorectal cancer, the functional significance of this protein remains unknown. The present study aimed to investigate the involvement of parkin expression in colorectal adenocarcinoma development and progression by evaluating the association between its expression, clinicopathological parameters, and expression of known proteins involved in colorectal cancer. Methods: Tissue microarrays consisting of 73 tumor and 64 normal tissue samples were generated to examine parkin expression and localization by immunohistochemistry. Results: A positive correlation of parkin and APC expression was observed in the superficial, intermediate, and profound regions of all cases (rho = 0.37; P = 0.001). Parkin expression was also significantly associated with tumors in men (P = 0.049), those of the mucinous subtype (P = 0.028), and of advanced stage (III + IV, P = 0.041). In addition, increased parkin expression was observed in the invasive front tumor region (P = 0.013). More importantly, a positive correlation was found between parkin expression and the overall survival of patients with advanced colorectal cancer (P = 0.019). Multivariate analysis showed that parkin expression was independent of any of the clinicopathological parameters evaluated in relation to patient survival. Conclusions: These results suggest that parkin expression status can be used as a potential independent prognostic marker of survival in advanced colorectal cancer.	[Veloso da Silva-Camargo, Claudia Caroline; Costacurta Polli, Nayanne Louise; Agostinho, Amanda Pereira; Olandosk, Marcia; de Noronha, Lucia; Sotomaior, Vanessa Santos] Pontificia Univ Catolica Parana PUCPR, Sch Hlth & Biosci, Grp Adv Mol Invest NIMA, BR-80215901 Curitiba, Parana, Brazil; [Svoboda Baldin, Rosimeri Kuhl; de Noronha, Lucia] Univ Fed Parana UFPR, Hosp Clin, BR-80215901 Curitiba, Parana, Brazil		da Silva-Camargo, CCV (corresponding author), Pontificia Univ Catolica Parana PUCPR, Sch Hlth & Biosci, Grp Adv Mol Invest NIMA, BR-80215901 Curitiba, Parana, Brazil.	claudia.veloso@pucpr.edu.br	Veloso, Claudia/AAJ-6694-2020; Sotomaior, Vanessa/AAX-4818-2020; noronha, lucia/F-6339-2015	Sotomaior, Vanessa/0000-0001-5388-6384; noronha, lucia/0000-0003-0310-7164			ABBAS AK, 2000, CELLULAR MOL IMMUNOL; BLENKINSOPP WK, 1981, J CLIN PATHOL, V34, P509, DOI 10.1136/jcp.34.5.509; Bonhin RG, 2014, BRAZ J OTORHINOLAR, V80, P290, DOI 10.1016/j.bjorl.2014.05.016; Cesari R, 2003, P NATL ACAD SCI USA, V100, P5956, DOI 10.1073/pnas.0931262100; Chen HC, 2009, HUM MOL GENET, V18, pR169, DOI 10.1093/hmg/ddp326; Chen JX, 2012, ASIAN PAC J CANCER P, V13, P3427, DOI 10.7314/APJCP.2012.13.7.3427; Chen JS, 2010, FEBS J, V277, P3028, DOI 10.1111/j.1742-4658.2010.07712.x; Chew MH, 2010, INT J COLORECTAL DIS, V25, P1221, DOI 10.1007/s00384-010-1033-3; Coussens LM, 2002, NATURE, V420, P860, DOI 10.1038/nature01322; Doss-Pepe EW, 2005, J BIOL CHEM, V280, P16619, DOI 10.1074/jbc.M413591200; Fallon L, 2006, NAT CELL BIOL, V8, P834, DOI 10.1038/ncb1441; Geisler S, 2010, NAT CELL BIOL, V12, P119, DOI 10.1038/ncb2012; Gong YX, 2017, NEOPLASIA, V19, P75, DOI 10.1016/j.neo.2016.12.006; Gong YX, 2014, NAT GENET, V46, P588, DOI 10.1038/ng.2981; Gorgoulis VG, 2005, NATURE, V434, P907, DOI 10.1038/nature03485; Hampe C, 2006, HUM MOL GENET, V15, P2059, DOI 10.1093/hmg/ddl131; Hugen N, 2016, NAT REV CLIN ONCOL, V13, P361, DOI 10.1038/nrclinonc.2015.140; Hyngstrom JR, 2012, ANN SURG ONCOL, V19, P2814, DOI 10.1245/s10434-012-2321-7; Ikeuchi K, 2009, INT J CANCER, V125, P2029, DOI 10.1002/ijc.24565; International Agency for Research on Cancer, EST INC MORT PREV WO; Kitada T, 1998, NATURE, V392, P605, DOI 10.1038/33416; Krizhanovsky V, 2008, COLD SH Q B, V73, P513, DOI 10.1101/sqb.2008.73.048; Lee JW, 2005, ONCOGENE, V24, P1477, DOI 10.1038/sj.onc.1208304; Lee S, 2016, ONCOTARGET, V7, P44211, DOI 10.18632/oncotarget.9954; Lim KL, 2005, J NEUROSCI, V25, P2002, DOI 10.1523/JNEUROSCI.4474-04.2005; Love RR, 2016, BREAST, V29, P188, DOI 10.1016/j.breast.2016.06.003; Manzanillo PS, 2013, NATURE, V501, P512, DOI 10.1038/nature12566; Matsuda N, 2010, J CELL BIOL, V189, P211, DOI 10.1083/jcb.200910140; McLelland GL, 2014, EMBO J, V33, P282, DOI 10.1002/embj.201385902; Narendra D, 2008, J CELL BIOL, V183, P795, DOI 10.1083/jcb.200809125; Nitsche U, 2013, ANN SURG, V258, P775, DOI 10.1097/SLA.0b013e3182a69f7e; Poulogiannis G, 2010, P NATL ACAD SCI USA, V107, P15145, DOI 10.1073/pnas.1009941107; Sakata E, 2003, EMBO REP, V4, P301, DOI 10.1038/sj.embor.embor764; Siegel R, 2013, CA-CANCER J CLIN, V63, P11, DOI 10.3322/caac.21166; Staropoli JF, 2003, NEURON, V37, P735, DOI 10.1016/S0896-6273(03)00084-9; Sun XD, 2013, CELL CYCLE, V12, P1133, DOI 10.4161/cc.24215; Tay SP, 2010, J BIOL CHEM, V285, P29231, DOI 10.1074/jbc.M110.108241; Tran TNH, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0025969; Ussakli CH, 2013, JNCI-J NATL CANCER I, V105, P1239, DOI 10.1093/jnci/djt167; Veeriah S, 2010, NAT GENET, V42, P77, DOI 10.1038/ng.491; Verhulst J, 2012, J CLIN PATHOL, V65, P381, DOI 10.1136/jclinpath-2011-200340; Vincow ES, 2013, P NATL ACAD SCI USA, V110, P6400, DOI 10.1073/pnas.1221132110; Vives-Bauza C, 2010, P NATL ACAD SCI USA, V107, P378, DOI 10.1073/pnas.0911187107; Wang F, 2004, GENE CHROMOSOME CANC, V40, P85, DOI 10.1002/gcc.20020; Yang MP, 2015, ONCOTARGET, V6, P7084, DOI 10.18632/oncotarget.3054; Yeo CWS, 2012, CANCER RES, V72, P2543, DOI 10.1158/0008-5472.CAN-11-3060; Zitvogel L, 2004, ADV IMMUNOL, V84, P131, DOI 10.1016/S0065-2776(04)84004-5	47	12	12	0	3	CHINESE ANTI-CANCER ASSOC	TIANJIN	TI-YUAN-BEI, HUANHU XI LU, HEXIQU, TIANJIN, 300060, PEOPLES R CHINA	2095-3941			CANCER BIOL MED	Cancer Biol. Med.	FEB	2018	15	1					61	69		10.20892/j.issn.2095-3941.2017.0136			9	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	FX1WD	WOS:000425841700007	29545969	Green Submitted, gold, Green Published			2022-04-25	
J	Tong, T; Niu, YH; Yue, Y; Wu, SC; Ding, H				Tong, Tao; Niu, Yun-Hui; Yue, Yuan; Wu, Shuang-chan; Ding, Hong			Beneficial effects of anthocyanins from red cabbage (Brassica oleracea L. var. capitata L.) administration to prevent irinotecan-induced mucositis	JOURNAL OF FUNCTIONAL FOODS			English	Article						Anthocyanins; Autophagy; Irinotecan; mTOR; Mucositis; Red cabbage	CLINICAL-PRACTICE GUIDELINES; OXIDATIVE STRESS; GASTROINTESTINAL MUCOSITIS; INTESTINAL MUCOSITIS; COLORECTAL-CANCER; MANAGEMENT; AUTOPHAGY; MICE; CHEMOTHERAPY; DIARRHEA	Intestinal mucositis is a common side effect of Irinotecan (CPT-11). Anthocyanins (ACs) from red cabbage against CPT-11-induced mucositis were studied. Mice were given CPT-11 (75 mg/kg, i.p. for 4 days) and treated with ACs (50, 100 mg/kg, i.g. for 7 days). On day 8, diarrhea and leukocyte count in blood were assessed. Samples of intestine were obtained for morphometric analysis, myeloperoxidase (MPO), TBARS and GSH assay. The effects of ACs on cytoprotection and intestinal permeability were studied in Caco-2 cells. ACs effectively reversed the signs of intestinal injury, including MPO activity, length of ileum and colon, leukopenia, intestinal architecture, and quantity of ileum mucus. In vitro, pretreatment with ACs enhanced transepithelial electrical resistance (TER) and the expression of ZO-1. Furthermore, the protective effects of ACs were associated to modulate autophagy through mTOR pathway. In conclusion, ACs from red cabbage are candidate for supplementary therapy of CPT-11-induced mucositis. (C) 2017 Elsevier Ltd. All rights reserved.	[Niu, Yun-Hui; Yue, Yuan; Wu, Shuang-chan; Ding, Hong] Wuhan Univ, MOE Key Lab Combinatorial Biosynth & Drug Discove, Wuhan 430072, Peoples R China; [Tong, Tao] Yangtze Univ, Affiliated Hosp 1, Dept Oncol, Jingzhou 434000, Peoples R China		Ding, H (corresponding author), Wuhan Univ, MOE Key Lab Combinatorial Biosynth & Drug Discove, Wuhan 430072, Peoples R China.	2313309477@qq.com; 542010762@qq.com; 178354235@qq.com; 1050444595@qq.com; dinghong1106@whu.edu.cn			National Natural Science Funds of ChinaNational Natural Science Foundation of China (NSFC) [81503356]	This work was supported by the National Natural Science Funds of China (81503356).	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Funct. Food.	MAY	2017	32						9	17		10.1016/j.jff.2017.01.051			9	Food Science & Technology; Nutrition & Dietetics	Science Citation Index Expanded (SCI-EXPANDED)	Food Science & Technology; Nutrition & Dietetics	ET4BU	WOS:000400224800002					2022-04-25	
J	Areti, A; Komirishetty, P; Akuthota, M; Malik, RA; Kumar, A				Areti, Aparna; Komirishetty, Prashanth; Akuthota, Manasaveena; Malik, Rayaz A.; Kumar, Ashutosh			Melatonin prevents mitochondrial dysfunction and promotes neuroprotection by inducing autophagy during oxaliplatin-evoked peripheral neuropathy	JOURNAL OF PINEAL RESEARCH			English	Article						autophagy; melatonin; mitochondrial dysfunction; oxaliplatin; oxidative/nitrosative stress; peripheral neuropathy	ROOT GANGLION NEURONS; NF-KAPPA-B; OXIDATIVE STRESS; QUALITY-CONTROL; BIOENERGETIC DEFICITS; NERVOUS-SYSTEM; ANTIOXIDANT; INJURY; SKIN; RATS	Oxaliplatin, an organoplatinum compound, is used in the treatment of colorectal cancer, but its clinical use can be limited due to the development of peripheral neuropathy. Whilst mitochondrial dysfunction has been implicated as a major pathomechanism for oxaliplatin-induced neurotoxicity, the prevention of autophagy may also aggravate neuronal cell death. Melatonin, a well-known mitoprotectant and autophagy inducer, was used to examine its neuroprotective role in oxaliplatin-induced peripheral neuropathy (OIPN). Melatonin prevented the loss of mitochondrial membrane potential (Psi m) and promoted neuritogenesis in oxaliplatin-challenged neuro-2a cells. It did not interfere with the cytotoxic activity of oxaliplatin in human colon cancer cell line, HT-29. Melatonin treatment significantly alleviated oxaliplatin-induced pain behavior and neuropathic deficits in rats. It also ameliorated nitro-oxidative stress mediated by oxaliplatin, thus prevented nitrosylation of proteins and loss of antioxidant enzymes, and therefore, it improved mitochondrial electron transport chain function and maintained cellular bioenergetics by improving the ATP levels. The protective effects of melatonin were attributed to preventing oxaliplatin-induced neuronal apoptosis by increasing the autophagy pathway (via LC3A/3B) in peripheral nerves and dorsal root ganglion (DRG). Hence, it preserved the epidermal nerve fiber density in oxaliplatin-induced neuropathic rats. Taken together, we provide detailed molecular mechanisms for the neuroprotective effect of melatonin and suggest it has translational potential for oxaliplatin-induced neuropathy.	[Areti, Aparna; Komirishetty, Prashanth; Akuthota, Manasaveena; Kumar, Ashutosh] Natl Inst Pharmaceut Educ & Res NIPER Hyderabad, Dept Pharmacol & Toxicol, Balanagar, India; [Komirishetty, Prashanth] Univ Alberta, Div Neurol Med Sci & Med Hlth Inst, Dept Med, Edmonton, AB, Canada; [Malik, Rayaz A.] Weill Cornell Med Qatar, Doha, Qatar; Univ Manchester, Inst Cardiovascular Med, Manchester, Lancs, England		Kumar, A (corresponding author), Natl Inst Pharmaceut Educ & Res NIPER Hyderabad, Dept Pharmacol & Toxicol, Balanagar, India.	ashutosh.niperhyd@gov.in	Kumar, Ashutosh/W-2265-2019; Malik, Rayaz/H-9231-2019; Kumar, Ashutosh/F-2719-2018	Kumar, Ashutosh/0000-0001-6659-4751; Malik, Rayaz/0000-0002-7188-8903; Kumar, Ashutosh/0000-0001-6659-4751	Department of Pharmaceuticals; Ministry of chemical and fertilizers; NIPER-Hyderabad; Department of Science and Technology, Govt of IndiaDepartment of Science & Technology (India) [DST/INT/UK/P-72/2014]; University of Manchester	Department of Pharmaceuticals; 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Pineal Res.	APR	2017	62	3							e12393	10.1111/jpi.12393			17	Endocrinology & Metabolism; Neurosciences; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Endocrinology & Metabolism; Neurosciences & Neurology; Physiology	EP3QS	WOS:000397297400005	28118492				2022-04-25	
J	Panzarini, E; Dini, L				Panzarini, Elisa; Dini, Luciana			Nanomaterial-Induced Autophagy: A New Reversal MDR Tool in Cancer Therapy?	MOLECULAR PHARMACEUTICS			English	Review						autophagy; nanosized drug delivery systems (DDSs); nanomaterials (NMs); cancer therapies; multidrug resistance (MDR)	CELL LUNG-CANCER; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; P-GLYCOPROTEIN; COLON-CANCER; THYMIDYLATE SYNTHASE; CROSS-PRESENTATION; CO-DELIVERY; SHELL NANOPARTICLES; ANTICANCER DRUG	Most of the therapeutic strategies to counteract cancer imply killing of malignant cells. The most exploited cell death mechanism in cancer therapies is apoptosis, but recently, a lot of papers report that other mechanisms, mainly autophagy, could represent a new line of attack in the fight against cancer. One of the limitations for the effectiveness of the approved clinical treatments is the phenomenon of multidrug resistance (MDR) which enables the cancer cells to develop resistance to therapy, especially for chemotherapy. The MDR mechanisms include (a) decreased uptake of drug, (b) reduced intracellular drug concentration by efflux pumps, (c) altered cell cycle checkpoints, (d) altered drug targets, (e) increased metabolism of drugs, (f) induced emergency response genes to impair apoptotic pathway, and (g) altered drug detoxification. Great efforts have been made to reverse MDR. Currently, autophagy and nanosized drug delivery systems (DDSs) belonging to nanomaterials (NMs) provide alternative strategies to circumvent MDR. Nanosized DDSs are very promising tools to accumulate chemotherapeutics at targeting sites and control temporal and spatial drug release into tumor cells. On the other hand, autophagy could overrule drug resistance upon its activation by ensuring cell death via switching its prosurvival role to a prodeath one or by mediating the occurrence of cell death, i.e., apoptosis or necrosis. Likewise, the autophagy inhibition could counteract MDR by sensitizing the cells to anticancer molecules, i.e., Src family tyrosine kinase (SFK) inhibitors or 5-fluorouracil. Noteworthy, autophagy has been recently indicated to be a common cellular response to NMs, corroborating the fascinating idea of the exploitation of NM-induced autophagy in nanomedicine therapy. This review focuses on recently published literature about the relationship between MDR reversal and NMs or autophagy pointing to hypothesize a pivotal role of autophagy modulation induced by NMs in counteracting MDR.	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Pharm.	AUG	2014	11	8					2527	2538		10.1021/mp500066v			12	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	AM6NW	WOS:000339982900004	24921216				2022-04-25	
J	Wu, DJ; Yin, ZH; Ji, YS; Li, L; Li, YX; Meng, FQ; Ren, XH; Xu, M				Wu, Dejun; Yin, Zhenhua; Ji, Yisheng; Li, Lin; Li, Yunxin; Meng, Fanqiang; Ren, Xiaohan; Xu, Ming			Identification of novel autophagy-related lncRNAs associated with a poor prognosis of colon adenocarcinoma through bioinformatics analysis	SCIENTIFIC REPORTS			English	Article							LONG NONCODING RNA; CANCER; CELLS; SUPPRESSION; EXPRESSION; PROMOTES; THERAPY	LncRNAs play a pivotal role in tumorigenesis and development. However, the potential involvement of lncRNAs in colon adenocarcinoma (COAD) needs to be further explored. All the data used in this study were obtained from The Cancer Genome Atlas database, and all analyses were conducted using R software. Basing on the seven prognosis-related lncRNAs finally selected, we developed a prognosis-predicting model with powerful effectiveness (training cohort, 1 year: AUC=0.70, 95% Cl=0.57-0.78; 3 years: AUC=0.71, 95% Cl=0.6-0.8; 5 years: AUC=0.76, 95% Cl=0.66-0.87; validation cohort, 1 year: AUC=0.70, 95% Cl=0.58-0.8; 3 years: AUC=0.73, 95% Cl=0.63-0.82; 5 years: AUC=0.68, 95% Cl=0.5-0.85). The VEGF and Notch pathway were analyzed through GSEA analysis, and low immune and stromal scores were found in high-risk patients (immune score, cor=-0.15, P<0.001; stromal score, cor=-0.18, P<0.001) , which may partially explain the poor prognosis of patients in the high-risk group. We screened lncRNAs that are significantly associated with the survival of patients with COAD and possibly participate in autophagy regulation. This study may provide direction for future research.	[Wu, Dejun; Xu, Ming] Fudan Univ, Shanghai Pudong Hosp, Dept Gen Surg, Pudong Med Ctr, Shanghai 201399, Peoples R China; [Yin, Zhenhua] Fudan Univ, Shanghai Pudong Hosp, Dept Digest, Pudong Med Ctr, 2800 Gongwei Rd, Shanghai 201399, Peoples R China; [Ren, Xiaohan] Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, State Key Lab Reprod, Nanjing 210029, Peoples R China; [Ji, Yisheng; Li, Lin; Li, Yunxin] Nanjing Med Univ, Clin Med Coll 1, Nanjing 210029, Peoples R China; [Meng, Fanqiang] Cent South Univ, Xiangya Med Coll, Changsha 410000, Hunan, Peoples R China		Xu, M (corresponding author), Fudan Univ, Shanghai Pudong Hosp, Dept Gen Surg, Pudong Med Ctr, Shanghai 201399, Peoples R China.; Ren, XH (corresponding author), Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, State Key Lab Reprod, Nanjing 210029, Peoples R China.	xiaohanren@njmu.edu.cn; xuming681025@sina.com			fund of Young Medical Talents Training Program of Pudong Health Committee of Shanghai [PWRq2020-67]; Discipline Construction Promoting Project of Shanghai Pudong Hospital [Zdxk2020-01, Zdzk2020-10]	This work was supported by the fund of Young Medical Talents Training Program of Pudong Health Committee of Shanghai (Grant No. PWRq2020-67); the Discipline Construction Promoting Project of Shanghai Pudong Hospital (Zdxk2020-01), (Zdzk2020-10).	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J	Nazim, UM; Moon, JH; Lee, YJ; Seol, JW; Park, SY				Nazim, Uddin Md.; Moon, Ji-Hong; Lee, You-Jin; Seol, Jae-Won; Park, Sang-Youel			PPAR gamma activation by troglitazone enhances human lung cancer cells to TRAIL-induced apoptosis via autophagy flux	ONCOTARGET			English	Article						troglitazone; PPAR gamma; autophagy; TRAIL; lung cancer cells	HUMAN BREAST-CANCER; DEATH RECEPTORS 4; COLON-CANCER; MEDIATED APOPTOSIS; SURFACE EXPRESSION; DOWN-REGULATION; UP-REGULATION; KAPPA-B; C-FLIP; LIGAND	Members of the tumor necrosis factor (TNF) transmembrane cytokine superfamily, such as TNFa and Fas ligand (FasL), play crucial roles in inflammation and immunity. TRAIL is a member of this superfamily with the ability to selectively trigger cancer cell death but does not motive cytotoxicity to most normal cells. Troglitazone are used in the cure of type II diabetes to reduce blood glucose levels and improve the sensitivity of an amount of tissues to insulin. In this study, we revealed that troglitazone could trigger TRAIL-mediated apoptotic cell death in human lung adenocarcinoma cells. Pretreatment of troglitazone induced activation of PPAR. in a dose-dependent manner. In addition conversion of LC3-I to LC3-II and PPAR. was suppressed in the presence of GW9662, a well-characterized PPAR. antagonist. Treatment with troglitazone resulted in a slight increase in conversion rate of LC3-I to LC3-II and significantly decreased p62 expression levels in a dose-dependent manner. This indicates that troglitazone induced autophagy flux activation in human lung cancer cells. Inhibition of autophagy flux applying a specific inhibitor and genetically modified ATG5 siRNA enclosed troglitazone-mediated enhancing effect of TRAIL. These data demonstrated that activation of PPAR. mediated by troglitazone enhances human lung cancer cells to TRAIL-induced apoptosis via autophagy flux and also suggest that troglitazone may be a combination therapeutic target with TRAIL protein in TRAIL-resistant cancer cells.	[Nazim, Uddin Md.; Moon, Ji-Hong; Lee, You-Jin; Seol, Jae-Won; Park, Sang-Youel] Chonbuk Natl Univ, Biosafety Res Inst, Coll Vet Med, Iksan 54596, Jeonbuk, South Korea		Park, SY (corresponding author), Chonbuk Natl Univ, Biosafety Res Inst, Coll Vet Med, Iksan 54596, Jeonbuk, South Korea.	sypark@chonbuk.ac.kr	Park, Sang-Youel/D-5966-2012	Park, Sang-Youel/0000-0003-0575-6045	National Research Foundation of Korea (NRF) - Korean government (MISP) [2013R1A4A1069486]	This study was supported by a grant from the National Research Foundation of Korea (NRF), funded by the Korean government (MISP) (2013R1A4A1069486).	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J	Zhang, ZY; Zhang, X; Huang, AM				Zhang, Zhiyong; Zhang, Xin; Huang, Aimin			Aggresome-Autophagy Associated Gene HDAC6 Is a Potential Biomarker in Pan-Cancer, Especially in Colon Adenocarcinoma	FRONTIERS IN ONCOLOGY			English	Article						pan-cancer; histone deacetylase 6; immune microenvironment; DNA methylation; immunotherapy	IMMUNE CELLS; EXPRESSION; PROGNOSIS; MORTALITY; BURDEN	Background: Histone deacetylase 6 (HDAC6) regulates cytoplasmic signaling networks through the deacetylation of various cytoplasmic substrates. Recent studies have identified the role of HDAC6 in tumor development and immune metabolism, but its specific function remains unclear. Methods: The current study determined the role of HDAC6 in tumor metabolism and tumor immunity through a multi-database pan-cancer analysis. The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) datasets were used to determine the expression levels, prognosis, tumor progression, immune checkpoints, and immune metabolism of HDAC6 in 33 tumors. Pathways, immune checkpoints, immune neoantigens, immune microenvironment, tumor mutational burden (TMB), microsatellite instability (MSI), DNA mismatch repair (MMR), and the value of methyltransferases. The R package was used for quantitative analysis and panoramic description. Results: In the present study, we determined that HDAC6 is differentially expressed in pan carcinomas, and by survival, we found that HDAC6 was generally associated with the prognosis of pancreatic adenocarcinoma, Thymoma, and uveal melanoma, where low expression of HDAC6 had a significantly worse prognosis. Secondly, through this experiment, we confirmed that HDAC6 expression level was associated with tumor immune infiltration and tumor microenvironment, especially in PAAD. Finally, HDAC6 was associated with immune neoantigen and immune checkpoint gene expression profiles in all cancers in addition to TMB and MSI in pan-cancers. Conclusion: HDAC6 is differentially expressed in pan-cancers and plays an essential role in tumor metabolism and immunity. HDAC6 holds promise as a tumor potential prognostic marker, especially in colon cancer.	[Zhang, Zhiyong; Zhang, Xin] Zhengzhou Univ, Dept Colorectal Surg, Affiliated Hosp 1, Zhengzhou, Peoples R China; [Huang, Aimin] Zhengzhou Univ, Dept Gen Surg, Med Coll, Zhengzhou, Peoples R China		Zhang, ZY (corresponding author), Zhengzhou Univ, Dept Colorectal Surg, Affiliated Hosp 1, Zhengzhou, Peoples R China.; Huang, AM (corresponding author), Zhengzhou Univ, Dept Gen Surg, Med Coll, Zhengzhou, Peoples R China.	zazzy1973@163.com; doctorhuang518@zzu.edu.cn					Banik D, 2020, CANCER RES, V80, P3649, DOI 10.1158/0008-5472.CAN-19-3738; Baretti M, 2018, PHARMACOL THERAPEUT, V189, P45, DOI 10.1016/j.pharmthera.2018.04.004; Bennett MR, 2017, CURR OPIN CHEM BIOL, V37, P97, DOI 10.1016/j.cbpa.2017.01.020; Blum A, 2018, CELL, V173, P530, DOI 10.1016/j.cell.2018.03.059; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Budnik LT, 2019, SCI TOTAL ENVIRON, V660, P593, DOI 10.1016/j.scitotenv.2019.01.055; Caja F, 2020, INT J MOL SCI, V21, DOI 10.3390/ijms21155561; Cerezo-Wallis D, 2016, CURR PHARM DESIGN, V22, P6234, DOI 10.2174/1381612822666160826111041; Chen G, 2018, NATURE, V560, P382, DOI 10.1038/s41586-018-0392-8; Chen L, 2017, ARTIF INTELL MED, V76, P27, DOI 10.1016/j.artmed.2017.02.001; Danilova L, 2019, CANCER IMMUNOL RES, V7, P886, DOI 10.1158/2326-6066.CIR-18-0822; Deskin B, 2016, SCI REP-UK, V6, DOI 10.1038/srep31086; Ding YX, 2019, MOL MED REP, V20, P3363, DOI 10.3892/mmr.2019.10571; Fitzmaurice C, 2017, JAMA ONCOL, V3, P524, DOI 10.1001/jamaoncol.2016.5688; Gajewski TF, 2013, NAT IMMUNOL, V14, P1014, DOI 10.1038/ni.2703; Gentles AJ, 2015, NAT MED, V21, P938, DOI 10.1038/nm.3909; Gupta D, 2019, DNA REPAIR, V78, P60, DOI 10.1016/j.dnarep.2019.03.009; He DD, 2020, CANCER MED-US, V9, P8782, DOI 10.1002/cam4.3486; Ijsselsteijn R, 2020, DNA REPAIR, V93, DOI 10.1016/j.dnarep.2020.102923; Jasiak NM, 2016, CRIT CARE NURS Q, V39, P227, DOI 10.1097/CNQ.0000000000000117; Jemal A, 2010, CANCER EPIDEM BIOMAR, V19, P1893, DOI 10.1158/1055-9965.EPI-10-0437; Kim I, 2018, BMC BIOINFORMATICS, V19, DOI 10.1186/s12859-018-2016-6; Knox T, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-42237-3; Lei X, 2020, CANCER LETT, V470, P126, DOI 10.1016/j.canlet.2019.11.009; Li TW, 2017, CANCER RES, V77, pE108, DOI 10.1158/0008-5472.CAN-17-0307; Liberzon A, 2011, BIOINFORMATICS, V27, P1739, DOI 10.1093/bioinformatics/btr260; Lonsdale J, 2013, NAT GENET, V45, P580, DOI 10.1038/ng.2653; Lv Z, 2016, MOL CARCINOGEN, V55, P1024, DOI 10.1002/mc.22345; Merino DM, 2020, J IMMUNOTHER CANCER, V8, DOI 10.1136/jitc-2019-000147; Miyake Y, 2016, NAT CHEM BIOL, V12, P748, DOI 10.1038/nchembio.2140; Moufarrij S, 2020, SCI REP-UK, V10, DOI 10.1038/s41598-020-60409-4; Nusinow DP, 2020, CELL, V180, P387, DOI 10.1016/j.cell.2019.12.023; Picard E, 2020, FRONT IMMUNOL, V11, DOI 10.3389/fimmu.2020.00369; Powers RK, 2018, BIOINFORMATICS, V34, P555, DOI 10.1093/bioinformatics/bty271; Schrock AB, 2019, ANN ONCOL, V30, P1096, DOI 10.1093/annonc/mdz134; Seymour L, 2017, LANCET ONCOL, V18, pE143, DOI 10.1016/S1470-2045(17)30074-8; Sharif T, 2019, AUTOPHAGY, V15, P686, DOI 10.1080/15548627.2018.1548547; Sokratous G, 2017, HUM VACC IMMUNOTHER, V13, P2575, DOI 10.1080/21645515.2017.1303582; Steg AD, 2014, ONCOTARGET, V5, P7065, DOI 10.18632/oncotarget.2295; Straker Norman, 2020, Psychodyn Psychiatry, V48, P1, DOI 10.1521/pdps.2020.48.1.1; Verdel A, 1999, J BIOL CHEM, V274, P2440, DOI 10.1074/jbc.274.4.2440; Wang ZY, 2020, CANCER MED-US, V9, P8086, DOI 10.1002/cam4.3410; Yang YF, 2018, ONCOL LETT, V16, P7295, DOI 10.3892/ol.2018.9513; Yin ZS, 2018, ONCOL LETT, V16, P7082, DOI 10.3892/ol.2018.9504; Zhang ZJ, 2017, CANCER BIOMARK, V19, P169, DOI 10.3233/CBM-160298; Zhou BL, 2021, FRONT MOL BIOSCI, V8, DOI 10.3389/fmolb.2021.648402	46	1	1	6	8	FRONTIERS MEDIA SA	LAUSANNE	AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND	2234-943X			FRONT ONCOL	Front. Oncol.	AUG 17	2021	11								718589	10.3389/fonc.2021.718589			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	UM6WM	WOS:000693470800001	34485153	gold, Green Published			2022-04-25	
J	Song, FL; Li, LX; Liang, DY; Zhuo, YS; Wang, XY; Dai, HC				Song, Fengling; Li, Lexing; Liang, Danyang; Zhuo, Yisha; Wang, Xueyi; Dai, Hanchuan			Knockdown of long noncoding RNA urothelial carcinoma associated 1 inhibits colorectal cancer cell proliferation and promotes apoptosis via modulating autophagy	JOURNAL OF CELLULAR PHYSIOLOGY			English	Article						apoptosis; autophagy; cell proliferation; colorectal cancer (CRC) cell; long noncoding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1)	PREDICTS POOR-PROGNOSIS; ACTIVATES AUTOPHAGY; TUMOR PROLIFERATION; UCA1; RESISTANCE; METASTASIS; EXPRESSION; MIGRATION; INJURY	Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been implicated in the growth and metastasis of colorectal cancer (CRC), and autophagy contributes to tumorigenesis and cancer cell survival. However, the regulatory role of UCA1 in CRC cell viability by modulating autophagy remains unclear. In the present study, a significant positive correlation was observed between UCA1 and microtubule-associated protein 1 light chain 3 (LC3) levels, and the elevated UCA1 was negatively correlated with the PKB/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in 293T cells. Downregulation of UCA1 inhibited autophagy activation and cell proliferation, whereas the apoptosis was increased and the cell cycle was arrested in G2 stage. The next results showed that UCA1 was markedly upregulated in Caco-2 cells. Knockdown of UCA1 significantly decreased the LC3-II and autophagy-related gene 5 (ATG5) protein levels and resulted in an increase in p62 expression. Conversely, the autophagy activator rapamycin (RAPA) reversed the effects. Furthermore, downregulated UCA1 decreased Caco-2 cells population in the G1 phase and increased the cells number in G2 phage. The cell proliferation was inhibited, and apoptosis rate was promoted. More important, RAPA could also abrogate the changes induced by knockdown of UCA1. Collectively, these data demonstrated that downregulated UCA1 induced autophagy inhibition, resulting in suppressing cell proliferation and promoting apoptosis, which suggested that UCA1 might serve as a potential new oncogene to regulate CRC cells viability by modulating autophagy.	[Song, Fengling; Li, Lexing; Liang, Danyang; Zhuo, Yisha; Wang, Xueyi; Dai, Hanchuan] Huazhong Agr Univ, Coll Vet Med, Dept Basic Vet Med, Wuhan, Hubei, Peoples R China		Dai, HC (corresponding author), Huazhong Agr Univ, Coll Vet Med, 1 Shizishan St, Wuhan 430070, Hubei, Peoples R China.	daihch@mail.hzau.edu.cn			National key RD Program [2016YFD0501210, 2017YFD0502301]; Natural Science Foundation of HubeiNatural Science Foundation of Hubei Province [2018CFB444]; Fundamental Research Funds for Central Universities of China [2011QC004]	National key R&D Program, Grant/Award Numbers: 2016YFD0501210, 2017YFD0502301; Natural Science Foundation of Hubei, Grant/Award Number: 2018CFB444; The Fundamental Research Funds for Central Universities of China, Grant/Award Number: 2011QC004	Amelio I, 2011, BIOCHEM BIOPH RES CO, V414, P277, DOI 10.1016/j.bbrc.2011.09.080; Bian ZH, 2016, SCI REP-UK, V6, DOI 10.1038/srep23892; Bussi C, 2017, SCI REP-UK, V7, DOI 10.1038/srep43153; Damas ND, 2016, NAT COMMUN, V7, DOI 10.1038/ncomms13875; Deng QW, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0103022; Fan Y, 2014, FEBS J, V281, P1750, DOI 10.1111/febs.12737; Fidler MM, 2017, INT J CANCER, V140, P2709, DOI 10.1002/ijc.30686; Gao JF, 2015, INT J CLIN EXP PATHO, V8, P12936; Gewirtz DA, 2014, J CELL PHYSIOL, V229, P6, DOI 10.1002/jcp.24420; Ghiam AF, 2017, ONCOTARGET, V8, P4668, DOI 10.18632/oncotarget.13576; Han F, 2018, J CELL BIOCHEM, V119, P1604, DOI 10.1002/jcb.26320; Hosseinpour-Moghaddam K., 2018, MOL MECH THERAPEUTIC, V233, P6524, DOI DOI 10.1002/jcp.26583; Indran IR, 2011, BBA-BIOENERGETICS, V1807, P735, DOI 10.1016/j.bbabio.2011.03.010; Ishikawa T, 2018, J CELL PHYSIOL, V233, P4825, DOI 10.1002/jcp.26285; Jiao CJ, 2016, ONCOL REP, V36, P2960, DOI 10.3892/or.2016.5121; Kang R, 2011, CELL DEATH DIFFER, V18, P571, DOI 10.1038/cdd.2010.191; Karantza-Wadsworth V, 2007, GENE DEV, V21, P1621, DOI 10.1101/gad.1565707; KASTAN MB, 1995, CANCER METAST REV, V14, P3, DOI 10.1007/BF00690207; Khachane AN, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0010316; Klionsky DJ, 2011, AUTOPHAGY, V7, P1273, DOI 10.4161/auto.7.11.17661; Kyo K, 2016, WORLD J GASTROENTERO, V22, P4604, DOI 10.3748/wjg.v22.i18.4604; Li L, 2016, MOL CANCER THER, V15, P2232, DOI 10.1158/1535-7163.MCT-16-0008; Li ZK, 2014, CANCER SCI, V105, P951, DOI 10.1111/cas.12461; Liu HY, 2016, PLOS ONE, V11, DOI 10.1371/journal.pone.0168406; Lu YH, 2017, GENE, V607, P41, DOI 10.1016/j.gene.2017.01.004; Maejima Y, 2013, NAT MED, V19, P1478, DOI 10.1038/nm.3322; Mercer TR, 2009, NAT REV GENET, V10, P155, DOI 10.1038/nrg2521; Ni BB, 2015, INT J ONCOL, V47, P1329, DOI 10.3892/ijo.2015.3109; Nie W, 2016, CANCER LETT, V371, P99, DOI 10.1016/j.canlet.2015.11.024; Otomo C, 2013, NAT STRUCT MOL BIOL, V20, P59, DOI 10.1038/nsmb.2431; Pawar K, 2016, SCI REP-UK, V6, DOI 10.1038/srep19416; Qiang L, 2014, P NATL ACAD SCI USA, V111, P9241, DOI 10.1073/pnas.1322913111; Ruhle F, 2016, GENOM PROTEOM BIOINF, V14, P191, DOI 10.1016/j.gpb.2016.03.001; Shan TD, 2016, ONCOTARGET, V7, P961, DOI 10.18632/oncotarget.5830; Siegel RL, 2015, CA-CANCER J CLIN, V65, P5, DOI [10.3322/caac.21254, 10.3322/caac.21208, 10.1001/jamaoto.2014.2530, 10.1136/bmj.g1502]; van der Vos KE, 2012, NAT CELL BIOL, V14, P829, DOI 10.1038/ncb2536; Wang J, 2017, AGING DIS, V8, P71, DOI 10.14336/AD.2016.0530; Wang XS, 2006, CLIN CANCER RES, V12, P4851, DOI 10.1158/1078-0432.CCR-06-0134; Wang Y, 2014, ONCOL LETT, V8, P1947, DOI 10.3892/ol.2014.2487; Wen JJ, 2017, EUR REV MED PHARMACO, V21, P498; Wu W, 2013, PLOS ONE, V8, DOI [10.1371/journal.pone.0059749, 10.1371/journal.pone.0059016]; Xiao JN, 2017, J CANCER RES CLIN, V143, P981, DOI 10.1007/s00432-017-2370-1; Xiu YL, 2017, ONCOTARGET, V8, P31727, DOI 10.18632/oncotarget.15955; Xu CG, 2016, EUR REV MED PHARMACO, V20, P4362; Xu ZJ, 2017, ONCOL REP, V37, P1359, DOI 10.3892/or.2017.5416; Yang C, 2012, GENE, V496, P8, DOI 10.1016/j.gene.2012.01.012; Yang F, 2013, J CANCER RES CLIN, V139, P437, DOI 10.1007/s00432-012-1324-x; Yang L, 2016, MOL BIOSYST, V12, P2605, DOI 10.1039/c6mb00114a; Ying L, 2013, MOL BIOSYST, V9, P407, DOI 10.1039/c2mb25386k; Yu WD, 2018, J CELL PHYSIOL, V233, P6518, DOI 10.1002/jcp.26568; Zeng MC, 2017, TOXICOL LETT, V271, P26, DOI 10.1016/j.toxlet.2017.02.023; Zhang J, 2016, BRAIN RES BULL, V125, P152, DOI 10.1016/j.brainresbull.2016.06.007; Zhang K, 2017, BIOSCIENCE REP, V37, DOI 10.1042/BSR20160239; Zhao W, 2017, CLIN TRANSL ONCOL, V19, P735, DOI 10.1007/s12094-016-1597-7; Zheng Q, 2015, CLIN TRANSL ONCOL, V17, P640, DOI 10.1007/s12094-015-1290-2; Zhu QQ, 2017, J CELL MOL MED, V21, P2184, DOI 10.1111/jcmm.13142; Zuo ZK, 2017, DNA CELL BIOL, V36, P159, DOI 10.1089/dna.2016.3553	57	19	19	0	25	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0021-9541	1097-4652		J CELL PHYSIOL	J. Cell. Physiol.	MAY	2019	234	5					7420	7434		10.1002/jcp.27500			15	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	HK7AQ	WOS:000458138600180	30362538				2022-04-25	
J	Shan, TD; Xu, JH; Yu, T; Li, JY; Zhao, LN; Ouyang, H; Luo, S; Lu, XJ; Huang, CZ; Lan, QS; Zhong, W; Chen, QK				Shan, Ti-Dong; Xu, Ji-Hao; Yu, Tao; Li, Jie-Yao; Zhao, Lin-Na; Ouyang, Hui; Luo, Su; Lu, Xi-Ji; Huang, Can-Ze; Lan, Qiu-Shen; Zhong, Wa; Chen, Qi-Kui			Knockdown of linc-POU3F3 suppresses the proliferation, apoptosis, and migration resistance of colorectal cancer	ONCOTARGET			English	Article						linc-POU3F3; colorectal cancer; proliferation; apoptosis; signal pathway	HEPATOCELLULAR-CARCINOMA; NONCODING RNAS; AUTOPHAGY; CELLS; EPIGENETICS; CARCINOGENESIS; TUMORIGENESIS; DEGRADATION; INVOLVEMENT; METASTASIS	Long intergenic noncoding RNAs (lincRNAs) play important roles in regulating the biological functions and underlying molecular mechanisms of colorectal cancer (CRC). Here, we investigated the association of linc-POU3F3 and prognosis in CRC. We demonstrated that linc-POU3F3 was overexpressed in CRC tissues and positively correlated with tumor grade and N stage. Inhibition of linc-POU3F3 resulted in inhibition of cell proliferation and G1 cell cycle arrest, which was mediated by cyclin D1, CDK4, p18, Rb, and phosphorylated Rb. Inhibition of linc-POU3F3 induced apoptosis, and suppressed migration and invasion in LOVO and SW480 cell lines. This inhibition also increased the expressions of epithelial markers and decreased the expressions of mesenchymal markers, thus inhibiting the cancer epithelial-mesenchymal transition. The decreased migration and invasion following linc-POU3F3 knockdown were mediated by an increased BMP signal. Furthermore, autophagy was enhanced by linc-POU3F3 knockdown, suggesting the involvement of autophagy in the induced apoptosis. Collectively, linc-POU3F3 might be crucial in pro-proliferation, anti-apoptosis, and metastasis in LOVO and SW480 cells by regulating the cell cycle, intrinsic apoptosis, BMP signaling and autophagy. Thus, linc-POU3F3 is a potential therapeutic target and novel molecular biomarker for CRC.	[Shan, Ti-Dong; Xu, Ji-Hao; Yu, Tao; Li, Jie-Yao; Ouyang, Hui; Luo, Su; Lu, Xi-Ji; Huang, Can-Ze; Zhong, Wa; Chen, Qi-Kui] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Gastroenterol, Guangzhou 510120, Guangdong, Peoples R China; [Shan, Ti-Dong; Xu, Ji-Hao; Yu, Tao; Li, Jie-Yao; Ouyang, Hui; Luo, Su; Lu, Xi-Ji; Huang, Can-Ze; Zhong, Wa; Chen, Qi-Kui] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Guangdong, Peoples R China; [Lan, Qiu-Shen] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Gen Surg, Guangzhou 510120, Guangdong, Peoples R China; [Zhao, Lin-Na] Guangzhou Univ Tradit Chinese Med, Affiliated Hosp 1, Dept Gastroenterol, Guangzhou 510504, Guangdong, Peoples R China		Yu, T; Chen, QK (corresponding author), Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Gastroenterol, Guangzhou 510120, Guangdong, Peoples R China.; Yu, T; Chen, QK (corresponding author), Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Guangdong, Peoples R China.	yutao2014@126.com; qikuichen@yahoo.com			Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology [[2013]163]; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes [KLB09001]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81270442, 81370475]	All authors read and approved the final manuscript. This work was supported by grants from the Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology (Grant [2013]163); the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes (Grant KLB09001); and the National Natural Science Foundation of China (No.81270442 and No. 81370475).	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J	Claerhout, S; Lim, JY; Choi, W; Park, YY; Kim, K; Kim, SB; Lee, JS; Mills, GB; Cho, JY				Claerhout, Sofie; Lim, Jae Yun; Choi, Woonyoung; Park, Yun-Yong; Kim, KyoungHyun; Kim, Sang-Bae; Lee, Ju-Seog; Mills, Gordon B.; Cho, Jae Yong			Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer	PLOS ONE			English	Article							HISTONE DEACETYLASE INHIBITORS; CONNECTIVITY MAP; SERIAL ANALYSIS; HUMAN COLON; CELL-DEATH; PHASE-II; CARCINOMA; GROWTH; AUTOPHAGY; RISK	Background: Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. Methodology/Principal Findings: Using microarray technology, we generated a gene expression profile of human gastric cancer-specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A) whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern. Conclusions/Significance: We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment.	[Claerhout, Sofie; Lim, Jae Yun; Park, Yun-Yong; Kim, Sang-Bae; Lee, Ju-Seog; Mills, Gordon B.; Cho, Jae Yong] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Div Canc Med, Houston, TX 77030 USA; [Lim, Jae Yun; Cho, Jae Yong] Yonsei Univ, Coll Med, Dept Med Oncol, Gangnam Severance Hosp, Seoul, South Korea; [Choi, Woonyoung] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA; [Kim, KyoungHyun] Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA		Claerhout, S (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Div Canc Med, Houston, TX 77030 USA.	chojy@yuhs.ac	Lee, Ju-Seog/X-1786-2018	Lee, Ju-Seog/0000-0002-5666-9753; Kim, Kyounghyun/0000-0002-7240-2768; Cho, Jae Yong/0000-0002-0926-1819; Claerhout, Sofie/0000-0003-0857-0211	Odyssey Program; University of Texas MD Anderson Cancer Center; National Research Foundation of KoreaNational Research Foundation of Korea; Ministry of Education, Science and TechnologyMinistry of Education, Science and Technology, Republic of Korea [2010-0024248]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA016672, P50CA098258] Funding Source: NIH RePORTER	Funding to SC as an Odyssey Fellow was supported by the Odyssey Program and the Theodore N. Law Endowment for Scientific Achievement at the University of Texas MD Anderson Cancer Center. This work was also supported by funds from the 2009 Internal Medicine Academic Research Fund and Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (No. 2010-0024248). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Alotaibi, MR; Asnake, B; Di, X; Beckman, MJ; Durrant, D; Simoni, D; Baruchello, R; Lee, RM; Schwartz, EL; Gewirtz, DA				Alotaibi, M. R.; Asnake, B.; Di, Xu; Beckman, M. J.; Durrant, D.; Simoni, D.; Baruchello, R.; Lee, R. M.; Schwartz, E. L.; Gewirtz, D. A.			Stilbene 5c, a microtubule poison with vascular disrupting properties that induces multiple modes of growth arrest and cell death	BIOCHEMICAL PHARMACOLOGY			English	Article						Microtubules; Autophagy; Senescence; Angiogenic; Vascular disrupting	COMBRETASTATIN A4 PHOSPHATE; DISSEMINATED MALIGNANT-MELANOMA; NATIONAL-CANCER-INSTITUTE; BREAST-CANCER; PHASE-III; MITOTIC CATASTROPHE; DRUG-RESISTANCE; CLINICAL-TRIALS; BETA-TUBULIN; AUTOPHAGY	The stilbene derivative, cis-3,4',5-trimethoxy-3'-aminostilbene (stilbene 5c), is a potentially potent antitumor agent that acts via binding to the colchicine-binding site in tubulin. The current studies were designed to investigate the effectiveness of stilbene 5c against the HCT-116 human colon cancer cell line and B16/F10 melanoma cells as well as human endothelial cell tube formation and tumor perfusion. Stilbene 5c produced a time-dependent decrease in cell viability in both cell lines and the capacity of the cells to proliferate was not restored upon removal of the drug. Treatment with stilbene 5c also promoted both senescence and autophagy in both cell lines. TUNEL and annexin 5 staining indicated that apoptosis also occurs in stilbene 5c-treated HCT-116 cells, but not in B16/F10 melanoma cells. DAPI staining revealed morphological changes in the cell nuclei (binucleated and micronucleated cells) indicative of mitotic catastrophe in HCT-116 cells but not in the B16/F10 melanoma cells. p53-null HCT-116 cells demonstrated a similar growth arrest/cell death response to stilbene as p53-wild type HCT-116 cells. Stilbene 5c also completely inhibited human endothelial cell tube formation on Matrigel, consistent with potential anti-angiogenic actions. Using a new method developed for monitoring the pharmacodynamic effects of stilbene 5c in vivo, we found that a single injection of stilbene 5c reduced tumor perfusion by 65% at 4 h, returning to baseline by 24 h, while subsequent daily injections of stilbene 5c produced progressively larger reductions and smaller rebounds. This work indicates that stilbene 5c could potentially be effective against melanoma and colon cancer through the promotion of multiple modes of growth arrest and cell death coupled with anti-angiogenic and antivascular actions. (C) 2013 Elsevier Inc. All rights reserved.	[Alotaibi, M. R.; Asnake, B.; Di, Xu; Beckman, M. J.; Lee, R. M.; Gewirtz, D. A.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA; [Alotaibi, M. R.; Asnake, B.; Di, Xu; Beckman, M. J.; Durrant, D.; Lee, R. M.; Gewirtz, D. A.] Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA; [Alotaibi, M. R.; Asnake, B.; Di, Xu; Beckman, M. J.; Durrant, D.; Lee, R. M.; Gewirtz, D. A.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA; [Simoni, D.; Baruchello, R.] Univ Ferrara, I-44100 Ferrara, Italy; [Schwartz, E. L.] Albert Einstein Coll Med, Dept Med Oncol, Bronx, NY 10461 USA		Gewirtz, DA (corresponding author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Med Coll Virginia Campus, Richmond, VA 23298 USA.	gewirtz@vcu.edu			NIH/NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [RO1 CA163907, RO1CA135043]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA135043, P30CA016059, R01CA163907] Funding Source: NIH RePORTER	This study was supported by NIH/NCI grants RO1 CA163907 (ELS) and RO1CA135043 (DAG). The guidance of Dr. Fiorenza lanzini of the University of Iowa Carver College of Medicine relating to studies of mitotic catastrophe is gratefully appreciated.	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Pharmacol.	DEC 15	2013	86	12					1688	1698		10.1016/j.bcp.2013.10.007			11	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	275XQ	WOS:000328713100006	24144631	Green Accepted			2022-04-25	
J	Handerson, T; Pawelek, JM				Handerson, T; Pawelek, JM			beta 1,6-branched oligosaccharides and coarse vesicles: A common, pervasive phenotype in melanoma and other human cancers	CANCER RESEARCH			English	Article							N-ACETYLGLUCOSAMINYLTRANSFERASE-V; BETA-1-6 BRANCHED OLIGOSACCHARIDES; ASPARAGINE-LINKED OLIGOSACCHARIDES; CELL-SURFACE; HUMAN-BREAST; ABERRANT GLYCOSYLATION; INCREASED EXPRESSION; HORIZONTAL TRANSFER; SIGNALING PATHWAY; TUMOR PROGRESSION	We describe a new phenotype of wide occurrence in human cancer: expression of coarse vesicles rich in beta1,6-branched oligosaccharides. beta1,6-branching, catalyzed by GNT-V, is associated with metastasis and predicts poor survival in primary human breast and colon carcinomas. Yet little is known on the histopathology of this phenomenon. We studied beta1,6-branching [determined by leukocytic phytohemagglutinin (LPHA) lectin-histochemistry] in 119 archival specimens of human melanomas and other neoplasms, including carcinomas of the lung, colon, breast, ovary, prostate, kidney, and Hodgkin's lymphoma. At least portions of most tumors (96%) stained to some extent with LPHA. Staining was always, but not exclusively, associated with coarse vesicles. In melanomas, LPHA staining colocalized with CD63 and gp100. In pigmented melanomas, the vesicles were melanized and are known as "coarse melanin." LPHA-positive, coarse melanin was a feature of both tumor cells and melanophages and accounted for the well-known hypermelanotic regions of primary melanomas. LPHA-positive tumor cells varied widely in primaries (melanoma and others), ranging from 0 to 100% for a given tumor, whereas metastases were far more homogeneous (P = 0.0080), with vesicular, LPHA-positive tumor cells comprising >75% of 15 of 16 metastatic melanomas and renal cell carcinomas. In studies by others, GNT-V elicited formation of autophagy-dependent, LPHA-positive vesicles in mink lung alveolar cells (Hariri et aL, Mol. Biol. Cell, 11: 255-268, 2000), suggesting that the coarse vesicles in tumors reported here may have been induced by GNT-V. Expression of the phenotype was so common and pervasive that it appeared to be an integral component of the biology of tumor progression. The origin of this phenotype and its biological significance are as yet unclear and will require considerable further study.	Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06520 USA		Pawelek, JM (corresponding author), Yale Univ, Sch Med, Dept Dermatol, 333 Cedar St, New Haven, CT 06520 USA.	john.pawelek@yale.edu			NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [P30AR041942] Funding Source: NIH RePORTER; NIAMS NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [2 P30 AR41942-06A1] Funding Source: Medline		Asada M, 1997, CANCER RES, V57, P1073; Asao T, 2001, CLIN EXP METASTAS, V18, P605; Aubert M, 2000, INT J CANCER, V88, P558, DOI 10.1002/1097-0215(20001115)88:4<558::AID-IJC7>3.0.CO;2-B; Bergsmedh A, 2002, CANCER RES, V62, P575; Bergsmedh A, 2001, P NATL ACAD SCI USA, V98, P6407, DOI 10.1073/pnas.101129998; 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SEP 1	2003	63	17					5363	5369					7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	722XD	WOS:000185402600030	14500369				2022-04-25	
J	Mujumdar, N; Banerjee, S; Chen, ZY; Sangwan, V; Chugh, R; Dudeja, V; Yamamoto, M; Vickers, SM; Saluja, AK				Mujumdar, Nameeta; Banerjee, Sulagna; Chen, Zhiyu; Sangwan, Veena; Chugh, Rohit; Dudeja, Vikas; Yamamoto, Masato; Vickers, Selwyn M.; Saluja, Ashok K.			Triptolide activates unfolded protein response leading to chronic ER stress in pancreatic cancer cells	AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY			English	Article						endoplasmic reticulum stress; apoptosis; autophagy; pancreatic cancer; triptolide; glucose-regulated protein 78	ENDOPLASMIC-RETICULUM STRESS; HEPATOCELLULAR-CARCINOMA; NEGATIVE REGULATOR; INDUCED APOPTOSIS; BREAST-CANCER; DEATH PROGRAM; COLON-CANCER; GRP78; EXPRESSION; AUTOPHAGY	Pancreatic cancer is a devastating disease with a survival rate of <5%. Moreover, pancreatic cancer aggressiveness is closely related to high levels of prosurvival mediators, which can ultimately lead to rapid disease progression. One of the mechanisms that enables tumor cells to evade cellular stress and promote unhindered proliferation is the endoplasmic reticulum (ER) stress response. Disturbances in the normal functions of the ER lead to an evolutionarily conserved cell stress response, the unfolded protein response (UPR). The UPR initially compensates for damage, but it eventually triggers cell death if ER dysfunction is severe or prolonged. Triptolide, a diterpene triepoxide, has been shown to be an effective compound against pancreatic cancer. Our results show that triptolide induces the UPR by activating the PKR-like ER kinase-eukaryotic initiation factor 2 alpha axis and the inositol-requiring enzyme 1 alpha-X-box-binding protein 1 axis of the UPR and leads to chronic ER stress in pancreatic cancer. Our results further show that glucose-regulated protein 78 (GRP78), one of the major regulators of ER stress, is downregulated by triptolide, leading to cell death by apoptosis in MIA PaCa-2 cells and autophagy in S2-VP10 cells.	[Mujumdar, Nameeta; Banerjee, Sulagna; Chen, Zhiyu; Sangwan, Veena; Chugh, Rohit; Dudeja, Vikas; Yamamoto, Masato; Vickers, Selwyn M.; Saluja, Ashok K.] Univ Minnesota, Dept Surg, Div Basic & Translat Res, Minneapolis, MN 55455 USA; [Yamamoto, Masato; Vickers, Selwyn M.; Saluja, Ashok K.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA		Saluja, AK (corresponding author), 11-214 Malcolm Moos Tower,515 Delaware St SE, Minneapolis, MN 55455 USA.	asaluja@umn.edu			University of Alabama Birmingham/University of Minnesota National Cancer Institute (NCI) Specialized Program of Research Excellence in Pancreatic Cancer Grant [P50 CA-101955]; NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01 CA-170946, CA-124723, T32 CA-132715]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P50CA101955, T32CA132715, R01CA124723, R01CA170946] Funding Source: NIH RePORTER	This study was supported by University of Alabama Birmingham/University of Minnesota National Cancer Institute (NCI) Specialized Program of Research Excellence in Pancreatic Cancer Grant P50 CA-101955 (to S. M. Vickers) and NCI Grants R01 CA-170946 and CA-124723 (to A. K. Saluja). R. Chugh was supported by NCI Training Grant T32 CA-132715.	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J. Physiol.-Gastroint. Liver Physiol.	JUN	2014	306	11					G1011	G1020		10.1152/ajpgi.00466.2013			10	Gastroenterology & Hepatology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology; Physiology	AI9FH	WOS:000337235900010	24699326	Green Published			2022-04-25	
J	Delle Cave, D; Desiderio, V; Mosca, L; Ilisso, CP; Mele, L; Caraglia, M; Cacciapuoti, G; Porcelli, M				Delle Cave, Donatella; Desiderio, Vincenzo; Mosca, Laura; Ilisso, Concetta P.; Mele, Luigi; Caraglia, Michele; Cacciapuoti, Giovanna; Porcelli, Marina			S-Adenosylmethionine-mediated apoptosis is potentiated by autophagy inhibition induced by chloroquine in human breast cancer cells	JOURNAL OF CELLULAR PHYSIOLOGY			English	Article						apoptosis; autophagy; chloroquine; drug combination; human breast cancer cell line MCF-7; S-Adenosylmethionine	IN-VITRO; HYPOMETHYLATION STATUS; OSTEOSARCOMA CELLS; LIVER-DISEASE; COLON-CANCER; GROWTH; METHYLATION; METHIONINE; EXPRESSION; PATHWAYS	The naturally occurring sulfonium compound S-adenosyl-L-methionine (AdoMet) is an ubiquitous sulfur-nucleoside that represents the main methyl donor in numerous methylation reactions. In recent years, it has been shown that AdoMet possesses antiproliferative properties in various cancer cells, but the molecular mechanisms at the basis of the effect induced by AdoMet have been only in part investigated. In the present study, we found that AdoMet strongly inhibited the proliferation of breast cancer cells MCF-7 by inducing both autophagy and apoptosis. AdoMet consistently enhanced the levels of the autophagy markers beclin-1 and LC3B-II, and caused a significant increase of pro-apoptotic Bax/Bcl-2 ratio paralleled by poly (ADP ribose) polymerase (PARP) and caspase 9, and 6 cleavage. Notably, AdoMet, already at low doses, raised the percentage of cells in G(2)/M phase of cell cycle by down-regulating the expression of cell cycle-regulatory proteins cyclin B and cyclin E with a remarkable increase of p53, p27, and p21. We also evaluated the combination of AdoMet and the autophagy inhibitor chloroquine (CLC) showing that autophagy block is synergistic in inducing both growth inhibition and apoptosis. These effects were paralleled by a strong inhibition of the activity of AKT and of the downstream effector mTOR and by an increased cleavage of caspase-6 and PARP. These data suggest, for the first time, that autophagy can act as an escape mechanism from the apoptotic activity of AdoMet, and that AdoMet could be used in combination with CLC or its analogs in the treatment of breast cancer.	[Delle Cave, Donatella; Mosca, Laura; Ilisso, Concetta P.; Caraglia, Michele; Cacciapuoti, Giovanna; Porcelli, Marina] Univ Campania Luigi Vanvitelli, Dept Biochem Biophys & Gen Pathol, Via L De Crecchio 7, I-80138 Naples, Italy; [Desiderio, Vincenzo; Mele, Luigi] Univ Campania Luigi Vanvitelli, Dept Expt Med, Naples, Italy		Caraglia, M (corresponding author), Univ Campania Luigi Vanvitelli, Dept Biochem Biophys & Gen Pathol, Via L De Crecchio 7, I-80138 Naples, Italy.	michele.caraglia@unina2.it	Mele, Luigi/AAC-9887-2019; Delle Cave, Donatella/AAM-2941-2021; desiderio, vincenzo/K-4244-2018; Caraglia, Michele/AAK-4569-2020	Mele, Luigi/0000-0002-6008-0802; Delle Cave, Donatella/0000-0002-4019-2778; Caraglia, Michele/0000-0003-2408-6091; desiderio, vincenzo/0000-0003-1819-6083; Mosca, Laura/0000-0001-7024-9192			Abraham J, 2015, EXPERT REV ANTICANC, V15, P51, DOI 10.1586/14737140.2015.961429; Ansorena E, 2002, HEPATOLOGY, V35, P274, DOI 10.1053/jhep.2002.30419; Anstee QM, 2012, J HEPATOL, V57, P1097, DOI 10.1016/j.jhep.2012.04.041; 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Cell. Physiol.	FEB	2018	233	2					1370	1383		10.1002/jcp.26015			14	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	FL9RB	WOS:000414593500057	28518408				2022-04-25	
J	Behl, T; Sharma, A; Sharma, L; Sehgal, A; Zengin, G; Brata, R; Fratila, O; Bungau, S				Behl, Tapan; Sharma, Aditi; Sharma, Lalit; Sehgal, Aayush; Zengin, Gokhan; Brata, Roxana; Fratila, Ovidiu; Bungau, Simona			Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives	BIOMEDICINES			English	Review						Withaferin A; anticancer; autophagy; chaperone	CELL-CYCLE ARREST; STEM-LIKE CELLS; BREAST-CANCER; WITHANIA-SOMNIFERA; MESENCHYMAL TRANSITION; COLON-CANCER; BETA-CATENIN; APOPTOSIS; WITHANOLIDES; AUTOPHAGY	Withaferin A (WA), a manifold studied, C28-steroidal lactone withanolide found in Withania somnifera. Given its unique beneficial effects, it has gathered attention in the era of modern science. Cancer, being considered a "hopeless case and the leading cause of death worldwide, and the available conventional therapies have many lacunae in the form of side effects. The poly pharmaceutical natural compound, WA treatment, displayed attenuation of various cancer hallmarks by altering oxidative stress, promoting apoptosis, and autophagy, inhibiting cell proliferation, reducing angiogenesis, and metastasis progression. The cellular proteins associated with antitumor pathways were also discussed. WA structural modifications attack multiple signal transduction pathways and enhance the therapeutic outcomes in various diseases. Moreover, it has shown validated pharmacological effects against multiple neurodegenerative diseases by inhibiting acetylcholesterinases and butyrylcholinesterases enzyme activity, antidiabetic activity by upregulating adiponectin and preventing the phosphorylation of peroxisome proliferator-activated receptors (PPAR gamma), cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis. The current review is an extensive survey of various WA associated disease targets, its pharmacokinetics, synergistic combination, modifications, and biological activities.	[Behl, Tapan; Sehgal, Aayush] Chitkara Univ, Chitkara Coll Pharm, Chandigarh 140401, Punjab, India; [Sharma, Aditi; Sharma, Lalit] Shoolini Univ, Sch Pharmaceut Sci, Solan 173229, Himachal Prades, India; [Zengin, Gokhan] Selcuk Univ Campus, Dept Biol, Fac Sci, TR-42250 Konya, Turkey; [Brata, Roxana; Fratila, Ovidiu] Univ Oradea, Fac Med & Pharm, Dept Med Disciplines, Oradea 410073, Romania; [Bungau, Simona] Univ Oradea, Fac Med & Pharm, Dept Pharm, Oradea 410028, Romania		Behl, T (corresponding author), Chitkara Univ, Chitkara Coll Pharm, Chandigarh 140401, Punjab, India.; Bungau, S (corresponding author), Univ Oradea, Fac Med & Pharm, Dept Pharm, Oradea 410028, Romania.	tapanbehl31@gmail.com; aditisharma31790@gmail.com; lalitluckysharma88@gmail.com; aayushsehgal00@gmail.com; biyologzengin@gmail.com; roxana.gavrila@yahoo.com; ovidiufr@yahoo.co.uk; sbungau@uoradea.ro	Fratila, Ovidiu Cristian/AAD-3419-2022; Bungau, Simona Gabriela/C-1831-2015; Brata, Roxana Daniela/AAD-4661-2022	Bungau, Simona Gabriela/0000-0003-3236-1292; Sharma, Dr. Lalit/0000-0001-9855-704X			Agarwalla P, 2016, NANOMEDICINE-UK, V11, P2529, DOI 10.2217/nnm-2016-0224; Alnuqaydan AM, 2020, AM J CANCER RES, V10, P799; Amin H, 2016, MOL CARCINOGEN, V55, P864, DOI 10.1002/mc.22328; Aranganathan S, 2005, CLIN BIOCHEM, V38, P535, DOI 10.1016/j.clinbiochem.2005.01.004; Atluri VSR, 2020, FRONT AGING NEUROSCI, V11, DOI 10.3389/fnagi.2019.00342; Bargagna-Mohan P, 2007, CHEM BIOL, V14, P623, DOI 10.1016/j.chembiol.2007.04.010; Bargagna-Mohan P, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0063881; Bartkova J, 2005, NATURE, V434, P864, DOI 10.1038/nature03482; Batumalaie K, 2016, SCI REP-UK, V6, DOI 10.1038/srep27236; Baud V, 2009, NAT REV DRUG DISCOV, V8, P33, DOI 10.1038/nrd2781; Behl T, 2020, LIFE SCI, V257, DOI 10.1016/j.lfs.2020.118075; Brenner DA, 2000, J HEPATOL, V32, P32, DOI 10.1016/S0168-8278(00)80413-4; Brunetti O, 2020, FRONT ONCOL, V10, DOI 10.3389/fonc.2020.00734; BRYAN TM, 1995, EMBO J, V14, P4240, DOI 10.1002/j.1460-2075.1995.tb00098.x; Cai JC, 2013, J CLIN INVEST, V123, P566, DOI 10.1172/JCI65871; Cereda V, 2014, EXPERT OPIN INV DRUG, V23, P469, DOI 10.1517/13543784.2014.885950; Chandrasekaran B, 2018, CARCINOGENESIS, V39, P1537, DOI 10.1093/carcin/bgy109; Chang HW, 2017, FRONT PHYSIOL, V8, DOI 10.3389/fphys.2017.00634; Chaudhary A, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-53568-6; Choudhary MI, 2004, CHEM PHARM BULL, V52, P1358, DOI 10.1248/cpb.52.1358; Cohen SM, 2012, AM J SURG, V204, P895, DOI 10.1016/j.amjsurg.2012.07.027; Cragg GM, 2013, BBA-GEN SUBJECTS, V1830, P3670, DOI 10.1016/j.bbagen.2013.02.008; Cuspidi C, 2006, NEPHROL DIAL TRANSPL, V21, P20, DOI 10.1093/ndt/gfi237; Dabelsteen E, 1996, J PATHOL, V179, P358; Dai MY, 2020, CANCER DISCOV, V10, P783, DOI 10.1158/2159-8290.CD-20-0422; Dai TM, 2019, BIOMED CHROMATOGR, V33, DOI 10.1002/bmc.4573; Das T, 2014, BIOCHEM PHARMACOL, V91, P31, DOI 10.1016/j.bcp.2014.06.022; Deng YB, 2008, NAT REV CANCER, V8, P450, DOI 10.1038/nrc2393; Deocaris CC, 2013, CURR PHARM DESIGN, V19, P418; Devi P. 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J	Liu, J; Xie, YL; Wu, SS; Lv, D; Wei, XM; Chen, F; Wang, ZL				Liu, Jun; Xie, Yaliu; Wu, Sisi; Lv, Dan; Wei, Xuemei; Chen, Fei; Wang, Zhenling			Combined effects of EGFR and hedgehog signaling blockade on inhibition of head and neck squamous cell carcinoma	INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY			English	Article						Malignant sinonasal tumors; EGFR; Hedgehog; apoptosis; autophagy	GROWTH-FACTOR RECEPTOR; TARGETED THERAPY; TUMOR-GROWTH; COPY NUMBER; HUMAN COLON; CANCER; SURVIVAL; BEHAVIOR; AUTOPHAGY; PATHWAYS	Head and neck cancer, the sixth most common cancer, has poor prognosis and short survival. Antiepidermal growth factor receptor ( EGFR) therapies have been recently developed for the treatment of multiple cancer types. JK184, an inhibitor of Hedgehog pathway, prevents the growth of many tumor cell lines in several studies. Whether it enhances chemosensitivity to block EGFR expression by shEGFR plasmid and blocks the Hedgehog pathway by JK184 remains unclear in sinonasal tumors. The changes in cell apoptosis and proteins have been detected by flow cytometry and Western blotting, respectively. In vivo, the maxillary sinus model was established to detect the inhibition of tumor growth and tumor weight. A synergistic effect has been observed with JK184 combined with shEGFR, which is positively correlated with increased autophagy. The maxillary sinus model results demonstrated that the inhibitory rate of the combined therapy was higher than that of JK184 or shEGFR alone. Our findings suggest that JK184 in combination with shEGFR might have potential as a new therapeutic regimen against sinonasal tumors.	[Liu, Jun; Lv, Dan; Chen, Fei] Sichuan Univ, West China Hosp, Dept Otorhinolaryngol Head & Neck Surg, Chengdu 610041, Sichuan, Peoples R China; [Xie, Yaliu] 7th Hosp Chengdu City, Dept Otorhinolaryngol, Chengdu, Sichuan, Peoples R China; [Wu, Sisi] Sichuan Univ, Core Facil, West China Hosp, Chengdu, Sichuan, Peoples R China; [Wu, Sisi; Wang, Zhenling] Sichuan Univ, Canc Ctr, West China Hosp, Chengdu 610041, Sichuan, Peoples R China; [Wu, Sisi; Wang, Zhenling] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China; [Wei, Xuemei] Chengdu 363 Hosp, Dept Otorhinolaryngol Head & Neck Surg, Chengdu, Sichuan, Peoples R China		Chen, F (corresponding author), Sichuan Univ, West China Hosp, Dept Otorhinolaryngol Head & Neck Surg, Chengdu 610041, Sichuan, Peoples R China.; Wang, ZL (corresponding author), Sichuan Univ, Canc Ctr, West China Hosp, Chengdu 610041, Sichuan, Peoples R China.; Wang, ZL (corresponding author), Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China.	375572059@qq.com; wangzhenling@scu.edu	, 刀客/ABG-3664-2020	Liu, Jun/0000-0003-4800-7749	Science and Technology department of Sichuan Pro-vince [2012SZ0024]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81000056]	The authors thank Shuang Zhang, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China, for providing the ShEGFR plasmid. This work was supported by the Science and Technology department of Sichuan Pro-vince (No. 2012SZ0024) and by a grant from the National Natural Science Foundation of China (No. 81000056).	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J. Clin. Exp. Pathol.		2017	10	9					9816	9828					13	Oncology; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pathology	FI7AU	WOS:000412148800086	31966869				2022-04-25	
J	Boland, CR				Boland, C. Richard			Chronic Inflammation, Colorectal Cancer and Gene Polymorphisms	DIGESTIVE DISEASES			English	Article; Proceedings Paper	173rd Falk Symposium From Chronic Inflammation to Cancer	JUN 04-05, 2010	Brno, CZECH REPUBLIC			Chronic inflammation; Colorectal cancer; Gene polymorphisms	GENOME-WIDE ASSOCIATION; AGE-OF-ONSET; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; ULCERATIVE-COLITIS; BOWEL-DISEASE; COLON-CANCER; RISK LOCI; HEREDITARY; VARIANTS	Chronic inflammation is commonly present in gastrointestinal mucosal sites at increased risk for cancer, such as in inflammatory bowel disease (IBD) or chronic gastritis caused by Helicobacter pylori infection. Why some patients have more mucosal inflammation than others, and why certain individuals with chronic inflammation develop cancer, are problems that have not been solved. Unlike the case for the syndromic forms of familial colorectal cancer (CRC), the risks for IBD and other forms of chronic inflammation have not been linked to highly penetrant single gene mutations. Single nucleotide polymorphisms (SNP) are variations in DNA sequence that can be linked to any phenotype (cancer, chronic inflammation, etc.) in genome-wide association studies (GWAS). CRC has been linked to several highly penetrant single gene loci, as well as multiple SNP. The propensity to develop IBD has not been linked to single gene mutations in most instances, but has been linked to SNP in the NOD2 locus (which appear to create hypomorphic alleles for this bacterial response gene), the IL23R locus, the autophagy gene ATG16L1 and a wide range of other loci including the Toll-like receptors, JAK2 and STAT3, and perhaps 70 more. At present, the problem in predicting risk for chronic inflammation is that there are many genetic polymorphisms with relatively modest individual effects. Our challenge is to understand how the SNPs that are linked to variations in the inflammatory response interact with one another (i.e. to understand the 'epistasis' involved), and to integrate this with the variety of individual environmental exposures. This represents an opportunity for informatics science to help personalize our approach to chronic inflammatory diseases of the gut and identify those at greatest risk for cancer. Copyright (C) 2010 S. Karger AG, Basel	[Boland, C. Richard] Baylor Univ, Med Ctr, Div Gastroenterol, GI Canc Res Lab, Dallas, TX 75246 USA		Boland, CR (corresponding author), Baylor Univ, Med Ctr, Div Gastroenterol, GI Canc Res Lab Hoblitzelle 250, 3500 Gaston Ave, Dallas, TX 75246 USA.	rickbo@baylorhealth.edu			Baylor Foundation; Baylor Research Institute; Sammons Cancer Center of Baylor University Medical Center; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R-01 CA72851]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA072851] Funding Source: NIH RePORTER	This work was supported by the Baylor Foundation, the Baylor Research Institute and the Sammons Cancer Center of Baylor University Medical Center. C.R.B. is the recipient of NIH Grant R-01 CA72851.	Abreu MT, 2002, GASTROENTEROLOGY, V123, P679, DOI 10.1053/gast.2002.35393; Barrett JC, 2008, NAT GENET, V40, P955, DOI 10.1038/ng.175; Boland CR, 2010, GASTROENTEROLOGY, V138, P2073, DOI [10.1053/j.gastro.2009.12.064, 10.1053/j.gastro.2010.04.024]; Campbell PT, 2007, CLIN CANCER RES, V13, P3783, DOI 10.1158/1078-0432.CCR-06-2987; De Jager PL, 2007, GENES IMMUN, V8, P387, DOI 10.1038/sj.gene.6364398; Duerr RH, 2006, SCIENCE, V314, P1461, DOI 10.1126/science.1135245; Esters N, 2004, AM J GASTROENTEROL, V99, P299, DOI 10.1111/j.1572-0241.2004.04040.x; Felix R, 2006, MUTAT RES-FUND MOL M, V602, P175, DOI 10.1016/j.mrfmmm.2006.09.004; Festen EAM, 2009, GUT, V58, P799, DOI 10.1136/gut.2008.166918; Fisher SA, 2008, NAT GENET, V40, P710, DOI 10.1038/ng.145; Frazier ML, 2001, CANCER RES, V61, P1269; Hugot JP, 2001, NATURE, V411, P599, DOI 10.1038/35079107; Imielinski M, 2009, NAT GENET, V41, P1335, DOI 10.1038/ng.489; Jaeger E, 2008, NAT GENET, V40, P26, DOI 10.1038/ng.2007.41; Jasperson KW, 2010, GASTROENTEROLOGY, V138, P2044, DOI 10.1053/j.gastro.2010.01.054; Jones JS, 2004, CLIN CANCER RES, V10, P5845, DOI 10.1158/1078-0432.CCR-03-0590; Jones JS, 2006, CANCER EPIDEM BIOMAR, V15, P886, DOI 10.1158/1055-9965.EPI-05-0644; Kong SM, 2000, CANCER RES, V60, P249; Krueger S, 2007, CANCER LETT, V252, P55, DOI 10.1016/j.canlet.2006.12.006; Libioulle C, 2007, PLOS GENET, V3, DOI 10.1371/journal.pgen.0030058; Martinez ME, 2003, P NATL ACAD SCI USA, V100, P7859, DOI 10.1073/pnas.1332465100; Mayer L, 2010, J GASTROENTEROL, V45, P9, DOI 10.1007/s00535-009-0138-3; McGovern DPB, 2010, NAT GENET, V42, P332, DOI 10.1038/ng.549; Ogura Y, 2001, NATURE, V411, P603, DOI 10.1038/35079114; Pomerantz MM, 2009, NAT GENET, V41, P882, DOI 10.1038/ng.403; Poynter JN, 2007, CANCER RES, V67, P11128, DOI 10.1158/0008-5472.CAN-07-3239; Rioux JD, 2007, NAT GENET, V39, P596, DOI 10.1038/ng2032; Shi Z, 2009, INT J CANCER, V125, P78, DOI 10.1002/ijc.24304; Silverberg MS, 2009, NAT GENET, V41, P216, DOI 10.1038/ng.275; Tenesa A, 2008, NAT GENET, V40, P631, DOI 10.1038/ng.133; Tomlinson IPM, 2010, BRIT J CANCER, V102, P447, DOI 10.1038/sj.bjc.6605338; Tomlinson I, 2007, NAT GENET, V39, P984, DOI 10.1038/ng2085; Tomlinson IPM, 2008, NAT GENET, V40, P623, DOI 10.1038/ng.111; Zanke BW, 2007, NAT GENET, V39, P989, DOI 10.1038/ng2089; Zecevic M, 2006, JNCI-J NATL CANCER I, V98, P139, DOI 10.1093/jnci/djj016	35	13	15	3	9	KARGER	BASEL	ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND	0257-2753	1421-9875		DIGEST DIS	Dig. Dis.		2010	28	4-5					590	595		10.1159/000320053			6	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED); Conference Proceedings Citation Index - Science (CPCI-S)	Gastroenterology & Hepatology	684LK	WOS:000284551200005	21088407	Green Published, Bronze			2022-04-25	
J	Park, SJ; Jo, DS; Jo, SY; Shin, DW; Shim, S; Jo, YK; Shin, JH; Ha, YJ; Jeong, SY; Hwang, JJ; Kim, YS; Suh, YA; Chang, JW; Kim, JC; Cho, DH				Park, So Jung; Jo, Doo Sin; Jo, Se-Young; Shin, Dong Woon; Shim, Sangmi; Jo, Yoon Kyung; Shin, Ji Hyun; Ha, Ye Jin; Jeong, Seong-Yun; Hwang, Jung Jin; Kim, Young Sam; Suh, Young-Ah; Chang, Jong Wook; Kim, Jin Cheon; Cho, Dong-Hyung			Inhibition of never in mitosis A (NIMA)-related kinase-4 reduces survivin expression and sensitizes cancer cells to TRAIL-induced cell death	ONCOTARGET			English	Article						NEK4; survivin; cancer; TRAIL	APOPTOSIS; QUERCETIN; RESISTANCE; AUTOPHAGY; NECROPTOSIS; PROGRESSION; COMPLEXITY; PATHWAYS; FAMILY	The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) preferentially induces apoptosis in cancer cells. However, many tumors are resistant to TRAIL-induced apoptosis, and resistance mechanisms are not fully understood. To identify novel regulatory molecules of TRAIL resistance, we screened a siRNA library targeting the human kinome, and NEK4 (NIMA-related kinase-4) was identified. Knockdown of NEK4 sensitized TRAIL-resistant cancer cells and in vivo xenografts to cell death. In contrast, over expression of NEK4 suppressed TRAIL-induced cell death in TRAIL-sensitive cancer cells. In addition, loss of NEK4 resulted in decrease of the antiapoptotic protein survivin, but an increase in apoptotic cell death. Interestingly, NEK4 was highly upregulated in tumor tissues derived from patients with lung cancer and colon cancer. These results suggest that inhibition of NEK4 sensitizes cancer cells to TRAIL-induced apoptosis by regulation of survivin expression.	[Park, So Jung; Jo, Doo Sin; Shin, Dong Woon; Jo, Yoon Kyung; Shin, Ji Hyun; Cho, Dong-Hyung] Kyung Hee Univ, Grad Sch East West Med Sci, Gyeonggi Do 17104, South Korea; [Jo, Se-Young; Ha, Ye Jin; Jeong, Seong-Yun; Hwang, Jung Jin; Suh, Young-Ah; Kim, Jin Cheon] Univ Ulsan, Coll Med, Asan Med Ctr, Asan Inst Med Res, Seoul 05505, South Korea; [Shim, Sangmi] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 03080, South Korea; [Kim, Young Sam] Yonsei Univ, Coll Med, Dept Internal Med, Seoul 03722, South Korea; [Chang, Jong Wook] Samsung Med Ctr, Res Inst Future Med, Stem Cell & Regenerat Med Inst, Seoul 06351, South Korea; [Chang, Jong Wook] Sungkyunkwan Univ, SAIHST, Dept Hlth Sci & Technol, Seoul 06351, South Korea; [Kim, Jin Cheon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Surg, Seoul 05505, South Korea		Chang, JW (corresponding author), Samsung Med Ctr, Res Inst Future Med, Stem Cell & Regenerat Med Inst, Seoul 06351, South Korea.; Chang, JW (corresponding author), Sungkyunkwan Univ, SAIHST, Dept Hlth Sci & Technol, Seoul 06351, South Korea.; Kim, JC (corresponding author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Surg, Seoul 05505, South Korea.	jongwook.chang@samsung.com; jckim@amc.seoul.kr	Hwang, Jung Jin/F-3424-2014		National Research Foundation [NRF-2013R1A2A1A03070986, 2013R1A1A1058361]; Ministry of Science, ICT, and Future Planning, Republic of Korea; Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea [HI14C3484]	This study was supported by grants from the National Research Foundation (NRF-2013R1A2A1A03070986 and 2013R1A1A1058361), Ministry of Science, ICT, and Future Planning, Republic of Korea, funded by the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI14C3484).	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J	Cosin-Roger, J; Simmen, S; Melhem, H; Atrott, K; Frey-Wagner, I; Hausmann, M; de Valliere, C; Spalinger, MR; Spielmann, P; Wenger, RH; Zeitz, J; Vavricka, SR; Rogler, G; Ruiz, PA				Cosin-Roger, Jesus; Simmen, Simona; Melhem, Hassan; Atrott, Kirstin; Frey-Wagner, Isabelle; Hausmann, Martin; de Valliere, Cheryl; Spalinger, Marianne R.; Spielmann, Patrick; Wenger, Roland H.; Zeitz, Jonas; Vavricka, Stephan R.; Rogler, Gerhard; Ruiz, Pedro A.			Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and autophagy activation	NATURE COMMUNICATIONS			English	Article							GENOME-WIDE ASSOCIATION; HIGH-ALTITUDE JOURNEYS; INDUCIBLE FACTOR-I; BOWEL-DISEASE; CROHNS-DISEASE; HIF HYDROXYLASES; GENE-EXPRESSION; CANCER CELLS; KAPPA-B; COLITIS	Hypoxia regulates autophagy and nucleotide-binding oligomerization domain receptor, pyrin domain containing (NLRP)3, two innate immune mechanisms linked by mutual regulation and associated to IBD. Here we show that hypoxia ameliorates inflammation during the development of colitis by modulating autophagy and mammalian target of rapamycin (mTOR)/NLRP3 pathway. Hypoxia significantly reduces tumor necrosis factor a, interleukin (IL)-6 and NLRP3 expression, and increases the turnover of the autophagy protein p62 in colon biopsies of Crohn's disease patients, and in samples from dextran sulfate sodium-treated mice and Il-10(-/-) mice. In vitro, NF-.kappa signaling and NLRP3 expression are reduced through hypoxia-induced autophagy. We also identify NLRP3 as a novel binding partner of mTOR. Dimethyloxalylglycine-mediated hydroxylase inhibition ameliorates colitis in mice, downregulates NLRP3 and promotes autophagy. We suggest that hypoxia counteracts inflammation through the downregulation of the binding of mTOR and NLRP3 and activation of autophagy.	[Cosin-Roger, Jesus; Simmen, Simona; Melhem, Hassan; Atrott, Kirstin; Frey-Wagner, Isabelle; Hausmann, Martin; de Valliere, Cheryl; Spalinger, Marianne R.; Zeitz, Jonas; Vavricka, Stephan R.; Rogler, Gerhard; Ruiz, Pedro A.] Univ Zurich, Univ Hosp Zurich, Dept Gastroenterol & Hepatol, Ramistr 100, CH-8091 Zurich, Switzerland; [Spielmann, Patrick; Wenger, Roland H.] Univ Zurich, Inst Physiol, Winterthurerstr 190, CH-8057 Zurich, Switzerland; [Spielmann, Patrick; Wenger, Roland H.; Rogler, Gerhard] Univ Zurich, Zurich Ctr Integrat Human Physiol ZIHP, CH-8057 Zurich, Switzerland		Ruiz, PA (corresponding author), Univ Zurich, Univ Hosp Zurich, Dept Gastroenterol & Hepatol, Ramistr 100, CH-8091 Zurich, Switzerland.	PedroAntonio.Ruiz-Castro@usz.ch	Wenger, Roland/B-7953-2009	Wenger, Roland/0000-0001-7592-4839; Hausmann, Martin/0000-0002-0696-0251; Cosin roger, Jesus/0000-0002-2468-4908; Spielmann, Patrick/0000-0001-7056-0351; Ruiz-Castro, Pedro Antonio/0000-0001-7528-1474	Swiss Philanthropy Foundation; Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission [324730_138291, 314730_153380]; Swiss IBD Cohort [314730_153380]; European Crohn's and Colitis Organisation (ECCO) Fellowship	We thank Mirjam Blattmann and Sylvie Scharl for their organizing and collecting the human colon biopsies. Mehdi Madanchi is gratefully acknowledged for his help in collecting the human subject data. We extend our special appreciation to Silvia Lang for her technical support, and the Zurich Integrative Rodent Physiology (ZIRP) core facility of the University of Zurich for their support in the animal experiments. This research was supported by a grant from the Swiss Philanthropy Foundation to GR and research grants from the Swiss National Science Foundation to GR (Grant No. 324730_138291 and 314730_153380), and the Swiss IBD Cohort (Grant No. 314730_153380). J.C.-R. was supported by the European Crohn's and Colitis Organisation (ECCO) Fellowship.	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Commun.	JUL 24	2017	8								98	10.1038/s41467-017-00213-3			13	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	FB5AN	WOS:000406153800001	28740109	Green Accepted, Green Published, gold			2022-04-25	
J	Patel, S; Hurez, V; Nawrocki, ST; Goros, M; Michalek, J; Sarantopoulos, J; Curiel, T; Mahalingam, D				Patel, Sukeshi; Hurez, Vincent; Nawrocki, Steffan T.; Goros, Martin; Michalek, Joel; Sarantopoulos, John; Curiel, Tyler; Mahalingam, Devalingam			Vorinostat and hydroxychloroquine improve immunity and inhibit autophagy in metastatic colorectal cancer	ONCOTARGET			English	Article						vorinostat; hydroxychloroquine; colorectal cancer; autophagy; immunity	REGULATORY T-CELLS; IN-VIVO; MICROSATELLITE INSTABILITY; TARGETING AUTOPHAGY; SOLID TUMORS; IMMUNOTHERAPY; COMBINATION; EXPRESSION; CARCINOMA; APOPTOSIS	Hydroxychloroquine (HCQ) enhances the anti-cancer activity of the histone deacetylase inhibitor, vorinostat (VOR), in pre-clinical models and early phase clinical studies of metastatic colorectal cancer (mCRC). Mechanisms could include autophagy inhibition, accumulation of ubiquitinated proteins, and subsequent tumor cell apoptosis. There is growing evidence that autophagy inhibition could lead to improved anticancer immunity. To date, effects of autophagy on immunity have not been reported in cancer patients. To address this, we expanded an ongoing clinical study to include patients with advanced, refractory mCRC to evaluate further the clinical efficacy and immune effects of VOR plus HCQ. Refractory mCRC patients received VOR 400 milligrams orally with HCQ 600 milligrams orally daily, in a 3-week cycle. The primary endpoint was median progression-free survival (mPFS). Secondary endpoints include median overall survival (mOS), adverse events (AE), pharmacodynamic of inhibition of autophagy in primary tumors, immune cell analyses, and cytokine levels. Twenty patients were enrolled (19 evaluable for survival) with a mPFS of 2.8 months and mOS of 6.7 months. Treatment-related grade 3-4 AEs occurred in 8 patients (40%), with fatigue, nausea/vomiting, and anemia being the most common. Treatment significantly reduced CD4(+)CD25(hi)Foxp3(+) regulatory and PD-1(+) (exhausted) CD4(+) and CD8(+) T cells and decreased CD45RO-CD62L(+) (naive) T cells, consistent with improved anti-tumor immunity. On-study tumor biopsies showed increases in lysosomal protease cathepsin D and p62 accumulation, consistent with autophagy inhibition. Taken together, VOR plus HCQ is active, safe and well tolerated in refractory CRC patients, resulting in potentially improved anti-tumor immunity and inhibition of autophagy.	[Patel, Sukeshi; Hurez, Vincent; Nawrocki, Steffan T.; Goros, Martin; Michalek, Joel; Sarantopoulos, John; Curiel, Tyler; Mahalingam, Devalingam] Univ Texas Hlth Sci Ctr San Antonio, Cancer Therapy & Res Ctr, San Antonio, TX 78229 USA		Mahalingam, D (corresponding author), Univ Texas Hlth Sci Ctr San Antonio, Cancer Therapy & Res Ctr, San Antonio, TX 78229 USA.	mahalingam@uthscsa.edu	Hurez, Vincent/AAF-6765-2019	Patel, Sukeshi/0000-0002-1176-0713; Hurez, Vincent/0000-0003-0271-4157	Cancer Therapy and Research Center (CTRC) Pilot Funding; Holly Beach Public Library Association; William and Ella Owens Foundation; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P30CA054174]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA054174] Funding Source: NIH RePORTER	Cancer Therapy and Research Center (CTRC) Pilot Funding (Devalingam Mahalingam); The Holly Beach Public Library Association (Tyler Curiel); The William and Ella Owens Foundation (Tyler Curiel); NIH grant P30CA054174 (All authors).	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J	Lv, Q; Wang, W; Xue, JF; Hua, F; Mu, R; Lin, H; Yan, J; Lv, XX; Chen, XG; Hu, ZW				Lv, Qi; Wang, Wei; Xue, Jianfei; Hua, Fang; Mu, Rong; Lin, Heng; Yan, Jun; Lv, Xiaoxi; Chen, Xiaoguang; Hu, Zhuo-Wei			DEDD Interacts with PI3KC3 to Activate Autophagy and Attenuate Epithelial-Mesenchymal Transition in Human Breast Cancer	CANCER RESEARCH			English	Article							DOMAIN-CONTAINING PROTEIN; TUMOR-METASTASIS; STEM-CELLS; DEATH; GROWTH; SNAIL; TWIST; PROGRESSION; COMPLEX; FAMILY	Epithelial-to-mesenchymal transition (EMT), a crucial developmental program, contributes to cancer invasion and metastasis. In this study, we show that death-effector domain-containing DNA-binding protein (DEDD) attenuates EMT and acts as an endogenous suppressor of tumor growth and metastasis. We found that expression levels of DEDD were conversely correlated with poor prognosis in patients with breast and colon cancer. Both in vitro and in vivo, overexpression of DEDD attenuated the invasive phenotype of highly metastatic cells, whereas silencing of DEDD promoted the invasion of nonmetastatic cells. Via direct interaction with the class III PI-3-kinase (PI3KC3)/Beclin1, DEDD activated autophagy and induced the degradation of Snail and Twist, two master regulators of EMT. The DEDD-PI3KC3 interaction led to stabilization of PI3KC3, which further contributed to autophagy and the degradation of Snail and Twist. Together, our findings highlight a novel mechanism in which the intracellular signaling protein DEDD functions as an endogenous tumor suppressor. DEDD expression therefore may represent a prognostic marker and potential therapeutic target for the prevention and treatment of cancer metastasis. Cancer Res; 72(13); 3238-50. (c) 2012 AACR.	[Lv, Qi; Wang, Wei; Xue, Jianfei; Hua, Fang; Mu, Rong; Lin, Heng; Yan, Jun; Lv, Xiaoxi; Chen, Xiaoguang; Hu, Zhuo-Wei] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Mol Immunol Grp, Beijing 100050, Peoples R China; [Lv, Qi; Wang, Wei; Xue, Jianfei; Hua, Fang; Mu, Rong; Lin, Heng; Yan, Jun; Lv, Xiaoxi; Chen, Xiaoguang; Hu, Zhuo-Wei] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Canc Pharmacol Grp, Beijing 100050, Peoples R China; [Lv, Qi; Wang, Wei; Xue, Jianfei; Hua, Fang; Mu, Rong; Lin, Heng; Yan, Jun; Lv, Xiaoxi; Chen, Xiaoguang; Hu, Zhuo-Wei] Peking Union Med Coll, Beijing 100050, Peoples R China		Hu, ZW (corresponding author), Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Mol Immunol Grp, Beijing 100050, Peoples R China.	huzhuowei@imm.ac.cn		Lv, Qi/0000-0001-9076-7042	National Major Basic Research Program of China (973)National Basic Research Program of China [2006CB503808]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81030056, 30973557, 81101595]; Creation of Major New Drugs [2009ZX09301-003-13, 2009ZX09301-003-9-1]	This work was supported by grants from National Major Basic Research Program of China (973: #2006CB503808), National Natural Science Foundation of China (81030056, 30973557, 81101595), and Creation of Major New Drugs (2009ZX09301-003-13, 2009ZX09301-003-9-1).	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JUL 1	2012	72	13					3238	3250		10.1158/0008-5472.CAN-11-3832			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	986OB	WOS:000307350700014	22719072	Bronze			2022-04-25	
J	Won, SJ; Yen, CH; Lin, TY; Jiang-Shieh, YF; Lin, CN; Chen, JT; Su, CL				Won, Shen-Jeu; Yen, Cheng-Hsin; Lin, Ting-Yu; Jiang-Shieh, Ya-Fen; Lin, Chun-Nan; Chen, Jyun-Ti; Su, Chun-Li			Autophagy mediates cytotoxicity of human colorectal cancer cells treated with garcinielliptone FC	JOURNAL OF CELLULAR PHYSIOLOGY			English	Article						apoptosis; autophagy; garcinielliptone FC; human colorectal cancer	NF-KAPPA-B; GARCINIA-SUBELLIPTICA; APOPTOSIS; THERAPY; DEATH; INFLAMMATION; EXPRESSION; SURVIVAL; PATHWAY; SYSTEM	The tautomeric pair of garcinielliptone FC (GFC) is a novel tautomeric pair of polyprenyl benzophenonoid isolated from the pericarps of Garcinia subelliptica Merr. (G. subelliptica, Clusiaceae), a tree with abundant sources of polyphenols. Our previous report demonstrated that GFC induced apoptosis on various types of human cancer cell lines including chemoresistant human colorectal cancer HT-29 cells. In the present study, we observed that many autophagy-related genes in GFC-treated HT-29 cells were up- and down-regulated using a cDNA microarray containing oncogenes and kinase genes. GFC-induced autophagy of HT-29 cells was confirmed by observing the formation of acidic vesicular organelles, LC3 puncta, and double-membrane autophagic vesicles using flow cytometry, confocal microscopy, and transmission electron microscopy, respectively. Inhibition of AKT/mTOR/P70S6K signaling as well as formation of Atg5-Atg12 and PI3K/Beclin-1 complexes were observed using Western blot. Administration of autophagy inhibitor (3-methyladenine and shRNA Atg5) and apoptosis inhibitor Z-VAD showed that the GFC-induced autophagy was cytotoxic form and GFC-induced apoptosis enhanced GFC-induced autophagy. Our data suggest the involvement of autophagy and apoptosis in GFC-induced anticancer mechanisms of human colorectal cancer.	[Won, Shen-Jeu; Lin, Ting-Yu] Natl Cheng Kung Univ, Dept Microbiol & Immunol, Coll Med, Tainan, Taiwan; [Yen, Cheng-Hsin; Chen, Jyun-Ti; Su, Chun-Li] Natl Taiwan Normal Univ, Dept Human Dev & Family Studies, 162,Sec 1,He Ping East Rd, Taipei 106, Taiwan; [Jiang-Shieh, Ya-Fen] Natl Cheng Kung Univ, Dept Anat, Coll Med, Tainan, Taiwan; [Lin, Chun-Nan] Kaohsiung Med Univ, Sch Pharm, Kaohsiung, Taiwan		Su, CL (corresponding author), Natl Taiwan Normal Univ, Dept Human Dev & Family Studies, 162,Sec 1,He Ping East Rd, Taipei 106, Taiwan.	chunlisu@ntnu.edu.tw			National Science CouncilMinistry of Science and Technology, Taiwan [98-2313-B-003-002-MY3, 101-2313-B-003-002MY3]; National Taiwan Normal University, Taiwan [103-07-C105T0700]; Ministry of Science and Technology, Taiwan MOST [104-2320-B-003-007]	National Science Council, Grant numbers: 98-2313-B-003-002-MY3, 101-2313-B-003-002MY3; National Taiwan Normal University, Taiwan, Grant number: 103-07-C105T0700; Ministry of Science and Technology, Taiwan MOST, Grant number: 104-2320-B-003-007	Aoki H, 2007, MOL PHARMACOL, V72, P29, DOI 10.1124/mol.106.033167; Burton TR, 2009, CELL DEATH DIFFER, V16, P515, DOI 10.1038/cdd.2008.185; Byun JY, 2009, CARCINOGENESIS, V30, P1880, DOI 10.1093/carcin/bgp235; Chang YP, 2010, J BIOL CHEM, V285, P28715, DOI 10.1074/jbc.M110.133355; Chen JJW, 1998, GENOMICS, V51, P313, DOI 10.1006/geno.1998.5354; Degenhardt K, 2006, CANCER CELL, V10, P51, DOI 10.1016/j.ccr.2006.06.001; Downward J, 2004, SEMIN CELL DEV BIOL, V15, P177, DOI 10.1016/j.semcdb.2004.01.002; Gewirtz DA, 2014, CANCER RES, V74, P647, DOI 10.1158/0008-5472.CAN-13-2966; Ito T, 2013, CHEM PHARM BULL, V61, P551, DOI 10.1248/cpb.c12-01057; Kang R, 2011, CELL DEATH DIFFER, V18, P571, DOI 10.1038/cdd.2010.191; Klionsky DJ, 2007, AUTOPHAGY, V3, P181, DOI 10.4161/auto.3678; Koehler BC, 2014, WORLD J GASTROENTERO, V20, P1923, DOI 10.3748/wjg.v20.i8.1923; Kondo Y, 2005, NAT REV CANCER, V5, P726, DOI 10.1038/nrc1692; Kondo Y, 2006, AUTOPHAGY, V2, P85, DOI 10.4161/auto.2.2.2463; Lan SH, 2014, HEPATOLOGY, V59, P505, DOI 10.1002/hep.26659; Lee JC, 2005, CARCINOGENESIS, V26, P1716, DOI 10.1093/carcin/bgi133; Lin KW, 2012, FOOD CHEM, V135, P851, DOI 10.1016/j.foodchem.2012.04.133; Lindqvist LM, 2014, AUTOPHAGY, V10, P1474, DOI 10.4161/auto.29639; Papandreou I, 2008, CELL DEATH DIFFER, V15, P1572, DOI 10.1038/cdd.2008.84; Rubinstein AD, 2012, J CELL SCI, V125, P5259, DOI 10.1242/jcs.115865; Saeed AI, 2003, BIOTECHNIQUES, V34, P374, DOI 10.2144/03342mt01; Tsai PC, 2008, ENVIRON RES, V108, P247, DOI 10.1016/j.envres.2008.07.006; Vaiopoulos AG, 2013, J MOL MED, V91, P1029, DOI 10.1007/s00109-013-1045-x; Won SJ, 2016, J FUNCT FOODS, V24, P568, DOI 10.1016/j.jff.2016.05.003; Won SJ, 2015, J CELL PHYSIOL, V230, P930, DOI 10.1002/jcp.24825; Wu CC, 2008, J NAT PROD, V71, P246, DOI 10.1021/np070507o; Xiao GT, 2007, CYTOKINE GROWTH F R, V18, P233, DOI 10.1016/j.cytogfr.2007.04.006; Yang N, 2008, PLOS ONE, V3, DOI 10.1371/journal.pone.0001758; Zhang Y, 2012, CLIN EXP MED, V12, P97, DOI 10.1007/s10238-011-0146-5	29	3	3	0	54	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0021-9541	1097-4652		J CELL PHYSIOL	J. Cell. Physiol.	JAN	2018	233	1					497	505		10.1002/jcp.25910			9	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	FI3BF	WOS:000411829600043	28294332				2022-04-25	
J	Liu, J; Hu, XJ; Jin, B; Qu, XJ; Hou, KZ; Liu, YP				Liu, Jing; Hu, Xue-Jun; Jin, Bo; Qu, Xiu-Juan; Hou, Ke-Zuo; Liu, Yun-Peng			ss-Elemene induces apoptosis as well as protective autophagy in human non-small-cell lung cancer A549 cells	JOURNAL OF PHARMACY AND PHARMACOLOGY			English	Article						apoptosis; autophagy; ss-elemene; lung cancer; mTOR	BETA-ELEMENE; GLIOBLASTOMA CELLS; MTOR PATHWAY; COLON-CANCER; ARREST; CYCLE; INHIBITION; THERAPY	Objectives beta-Elemene, a novel traditional Chinese medicine, has been shown to be effective against a wide range of tumours. In this study, the antitumour effect of beta-elemene on human non-small-cell lung cancer (NSCLC) A549 cells and the mechanism involved have been investigated. Methods Cell viability and apoptosis were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by Western blotting. Autophagy was evaluated under fluorescence microscopy and transmission electron microscopy. Key findings beta-Elemene inhibited the viability of A549 cells in a dose-dependent manner. This suppression of cell viability was due to the induction of apoptosis. Further study showed that beta-elemene inhibited the activity of the PI3K/Akt/mTOR/p70S6K1 signalling pathway, and at the same time it triggered a robust autophagy. The autophagy was characterized by the accumulation of punctate LC3 dots in the cytoplasm, morphological changes, and the increased levels of LC3-II as well as Atg5-Atg12 conjugated proteins. Inhibition of autophagy with chlorochine significantly enhanced the antitumour effect of beta-elemene. Conclusions Our data indicated that beta-elemene inhibited the activity of the PI3K/Akt/mTOR/p70S6K1 signalling pathway in human NSCLC A549 cells, which resulted in apoptosis as well as protective autophagy. A combination of beta-elemene with autophagy inhibitor might be an effective therapeutic option for advanced NSCLC.	[Liu, Jing; Jin, Bo; Qu, Xiu-Juan; Hou, Ke-Zuo; Liu, Yun-Peng] China Med Univ, Hosp 1, Dept Med Oncol, Shenyang 110001, Peoples R China; [Hu, Xue-Jun] China Med Univ, Hosp 1, Dept Resp Med, Shenyang 110001, Peoples R China		Liu, YP (corresponding author), China Med Univ, Hosp 1, Dept Med Oncol, Shenyang 110001, Peoples R China.	cmuliuyunpeng@yahoo.cn			First Hospital of China Medical University [fsfh1002]; Education Department of Liaoning Province [2008S246, 2008RC55, 20060945, 20060992]	This work was supported by the Fund for Scientific Research of The First Hospital of China Medical University, fsfh1002; Fund of The Education Department of Liaoning Province (NO. 2008S246, NO. 2008RC55, NO. 20060945, NO. 20060992).	Amaravadi RK, 2007, J CLIN INVEST, V117, P326, DOI 10.1172/JCI28833; Baldo P, 2008, CURR CANCER DRUG TAR, V8, P647, DOI 10.2174/156800908786733513; Beadsmoore CJ, 2003, EUR J RADIOL, V45, P8, DOI 10.1016/S0720-048X(02)00287-5; Chen WX, 2011, CANCER CHEMOTH PHARM, V67, P799, DOI 10.1007/s00280-010-1378-x; Cortes-Funes H, 2002, SEMIN ONCOL, V29, P26, DOI 10.1053/sonc.2002.33530; Dunn EF, 2011, ONCOGENE, V30, P561, DOI 10.1038/onc.2010.430; Guo R, 2010, BIOMED PHARMACOTHER, V64, P249, DOI 10.1016/j.biopha.2009.06.007; Houghton PJ, 2003, CURR TOP MICROBIOL, V279, P339; Jung CH, 2010, FEBS LETT, V584, P1287, DOI 10.1016/j.febslet.2010.01.017; Li J, 2010, J ASIAN NAT PROD RES, V12, P992, DOI 10.1080/10286020.2010.513034; Li QDQ, 2009, ONCOL REP, V22, P161, DOI 10.3892/or_00000420; Li QQ, 2010, J PHARM PHARMACOL, V62, P1018, DOI 10.1111/j.2042-7158.2010.01135.x; Li X, 2005, CELL MOL LIFE SCI, V62, P894, DOI 10.1007/s00018-005-5027-1; Li XQ, 2010, AUTOPHAGY, V6, P1066, DOI 10.4161/auto.6.8.13366; Mizushima N, 2007, GENE DEV, V21, P2861, DOI 10.1101/gad.1599207; Saiki S, 2011, AUTOPHAGY, V7, P176, DOI 10.4161/auto.7.2.14074; Sasaki K, 2010, BMC CANCER, V10, DOI 10.1186/1471-2407-10-370; Sun YH, 2009, BIOORGAN MED CHEM, V17, P1118, DOI 10.1016/j.bmc.2008.12.040; Tan P, 2000, Zhongguo Zhong Xi Yi Jie He Za Zhi, V20, P645; Thorburn A, 2008, APOPTOSIS, V13, P1, DOI 10.1007/s10495-007-0154-9; Thyagarajan A, 2010, NUTR CANCER, V62, P630, DOI 10.1080/01635580903532390; Wang G, 2005, CELL MOL LIFE SCI, V62, P881, DOI 10.1007/s00018-005-5017-3; Wang J, 1996, Zhonghua Zhong Liu Za Zhi, V18, P464; Wong TF, 2011, GYNECOL ONCOL, V122, P141, DOI 10.1016/j.ygyno.2011.03.001; Yang PM, 2010, CANCER RES, V70, P7699, DOI 10.1158/0008-5472.CAN-10-1626; Yang ZF, 2010, CURR OPIN CELL BIOL, V22, P124, DOI 10.1016/j.ceb.2009.11.014; Yao YQ, 2008, CANCER LETT, V264, P127, DOI 10.1016/j.canlet.2008.01.049; Zhao J, 2007, INT J ONCOL, V31, P241; Zhu K, 2010, ONCOGENE, V29, P451, DOI 10.1038/onc.2009.343; Zhu TZ, 2011, INT J ONCOL, V38, P419, DOI 10.3892/ijo.2010.855	30	45	53	1	14	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0022-3573	2042-7158		J PHARM PHARMACOL	J. Pharm. Pharmacol.	JAN	2012	64	1					146	153		10.1111/j.2042-7158.2011.01371.x			8	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	861ID	WOS:000298011700017	22150682				2022-04-25	
J	Yoshie, T; Nishiumi, S; Izumi, Y; Sakai, A; Inoue, J; Azuma, T; Yoshida, M				Yoshie, Tomoo; Nishiumi, Shin; Izumi, Yoshihiro; Sakai, Aya; Inoue, Jun; Azuma, Takeshi; Yoshida, Masaru			Regulation of the metabolite profile by an APC gene mutation in colorectal cancer	CANCER SCIENCE			English	Article							ADENOMATOUS POLYPOSIS; COLON; AUTOPHAGY; SERUM; METABOLOMICS; EXPRESSION; SARCOSINE; SURVIVAL; IDENTIFY; PROTEIN	Mutation of the APC gene occurs during the early stages of colorectal cancer development. To obtain new insights into the mechanisms underlying the aberrant activation of the Wnt pathway that accompanies APC mutation, we carried out a gas chromatographymass spectrometry-based semiquantitative metabolome analysis. In vitro experiments comparing SW480 cells expressing normal APC and truncated APC indicated that the levels of metabolites involved in the latter stages of the intracellular tricarboxylic acid cycle, including succinic acid, fumaric acid, and malic acid, were significantly higher in the SW480 cells expressing the truncated APC. In an in vivo study, we found that the levels of most amino acids were higher in the non-polyp tissues of APCmin/+ mice than in the normal tissues of the control mice and the polyp tissues of APCmin/+ mice. Ribitol, the levels of which were decreased in the polyp lesions of the APCmin/+ mice and the SW480 cells expressing the truncated APC, reduced the growth of SW480 cells with the APC mutation, but did not affect the growth of SW480 transfectants expressing full-length APC. The level of sarcosine was found to be significantly higher in the polyp tissues of APCmin/+ mice than in their non-polyp tissues and the normal tissues of the control mice, and the treatment of SW480 cells with 50 mu M sarcosine resulted in a significant increase in their growth rate. These findings suggest that APC mutation causes changes in energetic metabolite pathways and that these alterations might be involved in the development of colorectal cancer. (Cancer Sci 2012; 103: 10101021)	[Yoshie, Tomoo; Nishiumi, Shin; Izumi, Yoshihiro; Sakai, Aya; Inoue, Jun; Azuma, Takeshi; Yoshida, Masaru] Kobe Univ, Grad Sch Med, Dept Internal Med, Div Gastroenterol, Kobe, Hyogo 657, Japan; [Yoshida, Masaru] Kobe Univ, Grad Sch Med, Integrated Ctr Mass Spectrometry, Kobe, Hyogo 657, Japan; [Yoshida, Masaru] Kobe Univ, Grad Sch Med, Div Metabol Res, Kobe, Hyogo 657, Japan		Yoshida, M (corresponding author), Kobe Univ, Grad Sch Med, Dept Internal Med, Div Gastroenterol, Kobe, Hyogo 657, Japan.	myoshida@med.kobe-u.ac.jp	Nishiumi, Shin/ABD-5775-2020	Nishiumi, Shin/0000-0003-2126-3013	Global COE (Global Center of Excellence for Education and Research on Signal Transduction Medicine in the Coming Generation) from the Ministry of Education, Culture, Sports, Science, and Technology of JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Ministry of Agriculture, Forestry and Fisheries of JapanMinistry of Agriculture Forestry & Fisheries - Japan	This study was supported by grants from the Research Fellows of the Global COE Program (Global Center of Excellence for Education and Research on Signal Transduction Medicine in the Coming Generation) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to T.Y., M.Y., and T. A.), and from the Ministry of Agriculture, Forestry and Fisheries of Japan (Development of fundamental technology for analysis and evaluation of functional agricultural products and functional foods) (to M.Y.).	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JUN	2012	103	6					1010	1021		10.1111/j.1349-7006.2012.02262.x			12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	951ZA	WOS:000304758200006	22380946	Bronze, Green Published			2022-04-25	
J	Hu, YF; Li, X; Lin, L; Liang, ST; Yan, J				Hu, Yefang; Li, Xi; Lin, Ling; Liang, Siting; Yan, Jian			Puerarin inhibits non-small cell lung cancer cell growth via the induction of apoptosis	ONCOLOGY REPORTS			English	Article						puerarin; non-small cell lung cancer; cell growth; apoptosis; autophagy	COLON-CANCER; PRESSURE-OVERLOAD; NATURAL COMPOUNDS; IN-VIVO; ACTIVATION; ISOFLAVONES; PATHWAYS; HOMOLOG; BAX	Puerarin, an isoflavone isolated from Kudzu roots, has been demonstrated to have beneficial effect on cardiovascular and cerebral vascular diseases. Recently research has revealed that puerarin exerts an anticancer role in many different types of cancer. The aim of the present study was to investigate the antitumor effects of puerarin on non-small cell lung cancer (NSCLC). Treatment of puerarin significantly inhibited the growth of NSCLC cell lines as determined by CCK-8 kit in vitro. Flow cytometry results indicated that puerarin treatments promoted NSCLC cell apoptosis. This result was further confirmed by western blot analysis of expression levels of proteins involved in the mitochondrial-mediated apoptosis pathway. Moreover, puerarin slightly induced cell autophagy through the PI3K/Akt and MAPK/Erk1/2 signaling pathways. In addition, a tumor xenograft model was established using nude mice, and the inhibitory effects on tumor growth by puerarin treatment were also detected. Taken together, these findings demonstrated that puerarin has anticancer activities and puerarin is a potential therapeutic agent for lung cancer.	[Hu, Yefang; Lin, Ling; Liang, Siting; Yan, Jian] Guilin Tradit Chinese Med Hosp, Pharm Dept, Guilin 541002, Guangxi, Peoples R China; [Li, Xi] Guangxi Normal Univ, Key Lab Chem & Mol Engn Med Resources, 2 Lingui Rd, Guilin 541004, Guangxi, Peoples R China		Li, X (corresponding author), Guangxi Normal Univ, Key Lab Chem & Mol Engn Med Resources, 2 Lingui Rd, Guilin 541004, Guangxi, Peoples R China.	xi_li_china@hotmail.com			Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University) [CMEMR2016-B01]	This study was supported by the Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University) (CMEMR2016-B01).	Allemani C, 2015, LANCET, V385, P977, DOI 10.1016/S0140-6736(14)62038-9; Angulo P, 2017, J HEMATOL ONCOL, V10, DOI 10.1186/s13045-016-0373-z; Chanvorachote P, 2016, ANTICANCER RES, V36, P5707, DOI 10.21873/anticanres.11154; Choi YH, 2003, INT J ONCOL, V23, P1657; Devesa SS, 2005, INT J CANCER, V117, P294, DOI 10.1002/ijc.21183; Ferlay J, 2015, INT J CANCER, V136, pE359, DOI 10.1002/ijc.29210; Gross A, 1999, GENE DEV, V13, P1899, DOI 10.1101/gad.13.15.1899; Guo XF, 2015, MOL MED REP, V11, P2562, DOI 10.3892/mmr.2014.3016; Gupta SK, 2014, SOUTH ASIAN J CANCER, V3, P138, DOI 10.4103/2278-330X.130468; Han Jie, 2009, Zhongguo Zhong Xi Yi Jie He Za Zhi, V29, P632; Howlader N, SEER CANC STAT REV 1; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; Klionsky DJ, 2016, AUTOPHAGY, V12, P1, DOI 10.1080/15548627.2015.1100356; Lin YJ, 2009, BIOCHEM BIOPH RES CO, V378, P683, DOI 10.1016/j.bbrc.2008.10.178; Liu B, 2015, BIOCHEM BIOPH RES CO, V464, P908, DOI 10.1016/j.bbrc.2015.07.065; Ma YY, 2016, MED SCI MONITOR, V22, P977, DOI 10.12659/MSM.897379; National Research Council of the National Academies, 2011, GUID CAR US LAB AN 2; OLTVAI ZN, 1993, CELL, V74, P609, DOI 10.1016/0092-8674(93)90509-O; Pan MH, 2011, MOL NUTR FOOD RES, V55, P32, DOI 10.1002/mnfr.201000412; Schiller JH, 2002, NEW ENGL J MED, V346, P92, DOI 10.1056/NEJMoa011954; Shanmugam MK, 2016, SEMIN CANCER BIOL, V40-41, P35, DOI 10.1016/j.semcancer.2016.03.005; Swiatkowska B, 2015, LUNG CANCER, V89, P243, DOI 10.1016/j.lungcan.2015.06.013; Tian F, 2011, J ETHNOPHARMACOL, V134, P892, DOI 10.1016/j.jep.2011.01.055; Wang YC, 2013, INT J PHARMACEUT, V441, P728, DOI 10.1016/j.ijpharm.2012.10.021; Wei SY, 2014, CHIN J NAT MEDICINES, V12, P407, DOI 10.1016/S1875-5364(14)60064-9; Wong KH, 2011, J ETHNOPHARMACOL, V134, P584, DOI 10.1016/j.jep.2011.02.001; YANAGIHARA K, 1993, CANCER RES, V53, P5815; Yeung DKY, 2006, EUR J PHARMACOL, V552, P105, DOI 10.1016/j.ejphar.2006.08.078; Yu ZL, 2006, CANCER LETT, V238, P53, DOI 10.1016/j.canlet.2005.06.022; Yuan Y, 2014, J CARDIOL, V63, P73, DOI 10.1016/j.jjcc.2013.06.008; Zeng YP, 2014, ONCOL LETT, V8, P2436, DOI 10.3892/ol.2014.2534; Zhang SF, 2014, ASIAN PAC J CANCER P, V15, P10557, DOI 10.7314/APJCP.2014.15.24.10557; Zhang WG, 2014, MOL MED REP, V10, P2752, DOI 10.3892/mmr.2014.2512; Zhu GQ, 2012, NEUROCHEM INT, V60, P400, DOI 10.1016/j.neuint.2012.01.003	34	16	19	5	33	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1021-335X	1791-2431		ONCOL REP	Oncol. Rep.	APR	2018	39	4					1731	1738		10.3892/or.2018.6234			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GA2ZB	WOS:000428195300020	29393465	Bronze			2022-04-25	
J	Ropolo, A; Catrinacio, C; Renna, FJ; Boggio, V; Orquera, T; Gonzalez, CD; Vaccaro, MI				Ropolo, Alejandro; Catrinacio, Cintia; Renna, Felipe Javier; Boggio, Veronica; Orquera, Tamara; Gonzalez, Claudio D.; Vaccaro, Maria, I			A Novel E2F1-EP300-VMP1 Pathway Mediates Gemcitabine-Induced Autophagy in Pancreatic Cancer Cells Carrying Oncogenic KRAS	FRONTIERS IN ENDOCRINOLOGY			English	Article						pancreatic cancer; gemcitabine; autophagy; VMP1	VMP1 EXPRESSION; RESISTANCE; E2F1; ADENOCARCINOMA; APOPTOSIS; TRANSCRIPTION; CHEMOTHERAPY; PROGRESSION; MACHINERY; OVERCOME	Autophagy is an evolutionarily preserved degradation process of cytoplasmic cellular constituents, which participates in cell response to disease. We previously characterized VMP1 (Vacuole Membrane Protein 1) as an essential autophagy related protein that mediates autophagy in pancreatic diseases. We also demonstrated that VMP1-mediated autophagy is induced by HIF-1A (hypoxia inducible factor 1 subunit alpha) in colon-cancer tumor cell lines, conferring resistance to photodynamic treatment. Here we identify a new molecular pathway, mediated by VMP1, by which gemcitabine is able to trigger autophagy in human pancreatic tumor cell lines. We demonstrated that gemcitabine requires the VMP1 expression to induce autophagy in the highly resistant pancreatic cancer cells PANC-1 and MIAPaCa-2 that carry activatedKRAS. E2F1 is a transcription factor that is regulated by the retinoblastoma pathway. We found that E2F1 is an effector of gemcitabine-induced autophagy and regulates the expression and promoter activity of VMP1. Chromatin immunoprecipitation assays demonstrated that E2F1 binds to theVMP1promoter in PANC-1 cells. We have also identified the histone acetyltransferase EP300 as a modulator of VMP1 promoter activity. Our data showed that the E2F1-EP300 activator/co-activator complex is part of the regulatory pathway controlling the expression and promoter activity of VMP1 triggered by gemcitabine in PANC-1 cells. Finally, we found that neither VMP1 nor E2F1 are induced by gemcitabine treatment in BxPC-3 cells, which do not carry oncogenic KRAS and are sensitive to chemotherapy. In conclusion, we have identified the E2F1-EP300-VMP1 pathway that mediates gemcitabine-induced autophagy in pancreatic cancer cells. These results strongly support that VMP1-mediated autophagy may integrate the complex network of events involved in pancreatic ductal adenocarcinoma chemo-resistance. Our experimental findings point at E2F1 and VMP1 as novel potential therapeutic targets in precise treatment strategies for pancreatic cancer.	[Ropolo, Alejandro; Catrinacio, Cintia; Renna, Felipe Javier; Boggio, Veronica; Orquera, Tamara; Gonzalez, Claudio D.; Vaccaro, Maria, I] Univ Buenos Aires, Sch Pharm & Biochem, Inst Biochem & Mol Med, Dept Pathophysiol,UBA CONICET, Buenos Aires, DF, Argentina; [Gonzalez, Claudio D.] CEMIC Univ Inst, Buenos Aires, DF, Argentina		Ropolo, A (corresponding author), Univ Buenos Aires, Sch Pharm & Biochem, Inst Biochem & Mol Med, Dept Pathophysiol,UBA CONICET, Buenos Aires, DF, Argentina.	aropolo@ffyb.uba.ar		Gonzalez, Claudio/0000-0002-3772-8850	Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) [PIP 2015-2017 GI-11220150100160CO]; Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT)ANPCyT [PICT20132048, PICT2016-1032]; Universidad de Buenos AiresUniversity of Buenos Aires [UBACYT 2014-2017 GC-20020130100764BA, UBACyT 2018-2020-20020170100082BA]	This work was supported by grants from: Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) [PIP 2015-2017 GI-11220150100160CO]; Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT) [PICT20132048; PICT2016-1032] and Universidad de Buenos Aires [UBACYT 2014-2017 GC-20020130100764BA; UBACyT 2018-2020-20020170100082BA].	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Endocrinol.	JUN 23	2020	11								411	10.3389/fendo.2020.00411			14	Endocrinology & Metabolism	Science Citation Index Expanded (SCI-EXPANDED)	Endocrinology & Metabolism	MK3DM	WOS:000548664100001	32655498	Green Published, gold			2022-04-25	
J	Chu, CA; Lee, CT; Lee, JC; Wang, YW; Huang, CT; Lan, SH; Lin, PC; Lin, BW; Tian, YF; Liu, HS; Chow, NH				Chu, Chien-An; Lee, Chung-Ta; Lee, Jenq-Chang; Wang, Yi-Wen; Huang, Ching-Tang; Lan, Sheng-Hui; Lin, Peng-Chan; Lin, Bo-Wen; Tian, Yu-Feng; Liu, Hsiao-Sheng; Chow, Nan-Haw			MiR-338-5p promotes metastasis of colorectal cancer by inhibition of phosphatidylinositol 3-kinase, catalytic subunit type 3-mediated autophagy pathway	EBIOMEDICINE			English	Article						miR-338-5p; PIK3C3; Autophagy and colorectal cancer	SUPPRESSES TUMORIGENESIS; SIGNALING PATHWAY; CELL-MIGRATION; EXPRESSION; MICRORNA; IDENTIFICATION; PROLIFERATION; PROGNOSIS; CARCINOMA; INVASION	Background: In our preliminary screening, expression of miR-338-5p was found to be higher in primary colorectal cancer (CRC) with metastasis. The autophagy related gene- phosphatidylinositol 3-kinase, catalytic subunit type 3 (PIK3C3) appeared to be targeted by miR-338-5p. Here, we provide solid evidence in support of PIK3C3 involved in miR-338-5p related metastasis of CRC in vitro and in vivo. Methods: The potential clinical relevance of miR-338-5p and its target gene was analysed on benign colorectal polyps and primary CRCs by QPCR Mouse spleen xenograft experiment was performed to examine the importance of miR-338-5p for metastasis. Findings: PIK3C3 was one of target genes of miR-338-5p. In primary CRCs, expression of miR-338-5p is positively related to tumour staging, distant metastasis and poor patient survival. Patients with higher ratios of miR-338-5p/PIK3C3 also had significantly poor overall survival, supporting their significance in the progression of CRC. Over-expression of miR-338-5p promotes CRC metastasis to the liver and lung in vivo, in which PIK3C3 was down-regulated in the metastatic tumours. In contrast, overexpression of PIK3C3 in miR-338-5p stable cells inhibited the growth of metastatic tumours. Both migration and invasion of CRC in vitro induced by miR-338-5p are mediated by suppression of PIK3C3. Using forward and reverse approaches, autophagy was proved to involve in CRC migration and invasion induced by miR-338-5p. Interpretation: MiR-338-5p induces migration, invasion and metastasis of CRC in part through PIK3C3-related autophagy pathway. The miR-338-5p/PIK3C3 ratio may become a prognostic biomarker for CRC patients. (C) 2019 Published by Elsevier B.V.	[Chu, Chien-An; Huang, Ching-Tang; Lan, Sheng-Hui; Liu, Hsiao-Sheng; Chow, Nan-Haw] Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan, Taiwan; [Lee, Chung-Ta; Wang, Yi-Wen; Chow, Nan-Haw] Natl Cheng Kung Univ Hosp, Dept Pathol, Tainan, Taiwan; [Lee, Chung-Ta; Wang, Yi-Wen; Chow, Nan-Haw] Natl Cheng Kung Univ, Coll Med, Tainan, Taiwan; [Lee, Chung-Ta] Natl Cheng Kung Univ Hosp, Dept Pathol, Dou Liou Branch, Douliou City, Yunlin, Taiwan; [Lee, Jenq-Chang; Lin, Bo-Wen] Natl Cheng Kung Univ Hosp, Coll Med, Dept Surg, Tainan, Taiwan; [Lan, Sheng-Hui] Natl Yang Ming Univ, Dept Life Sci, Taipei, Taiwan; [Lan, Sheng-Hui] Natl Yang Ming Univ, Inst Genome Sci, Taipei, Taiwan; [Liu, Hsiao-Sheng] Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, 1 Univ Rd, Tainan 701, Taiwan; [Lin, Peng-Chan] Natl Cheng Kung Univ, Coll Med, Dept Internal Med, Tainan, Taiwan; [Tian, Yu-Feng] Chia Nan Univ Pharm & Sci, Dept Hlth & Nutr, Tainan, Taiwan; [Tian, Yu-Feng] Chi Mei Med Ctr, Dept Surg, Div Colorectal Surg, Tainan, Taiwan		Liu, HS (corresponding author), Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, 1 Univ Rd, Tainan 701, Taiwan.; Chow, NH (corresponding author), Natl Cheng Kung Univ, Coll Med, Dept Pathol, 1 Univ Rd, Tainan 701, Taiwan.	a713@mail.ncku.edu.tw; chownh@mail.ncku.edu.tw	Lan, Sheng-Hui/AAV-1662-2021	Liu, Hsiao-Sheng/0000-0003-0576-7203	National Cheng Kung University Hospital, Tainan, TAIWAN [NCKUH-10704015]; Ministry of Science and Technology, TAIWANMinistry of Science and Technology, Taiwan [MOST-105-2320-B-006 -029 -MY3]	This work was supported by research grant NCKUH-10704015 from the National Cheng Kung University Hospital, Tainan, TAIWAN and grant MOST-105-2320-B-006 -029 -MY3 from the Ministry of Science and Technology, TAIWAN. The funders have no role in the study design, data collection, data analysis, interpretation, and writing of the report.U	Balgi AD, 2009, PLOS ONE, V4, DOI 10.1371/journal.pone.0007124; Barik S, 2008, NUCLEIC ACIDS RES, V36, P5232, DOI 10.1093/nar/gkn513; Besse A, 2016, TUMOR BIOL, V37, P7719, DOI 10.1007/s13277-015-4654-x; Bilegsaikhan E, 2018, J DIGEST DIS, V19, P404, DOI 10.1111/1751-2980.12643; Budhu A, 2008, HEPATOLOGY, V47, P897, DOI 10.1002/hep.22160; Carthew RW, 2009, CELL, V136, P642, DOI 10.1016/j.cell.2009.01.035; Chen CH, 2018, CLIN CANCER RES, V24, P1176, DOI 10.1158/1078-0432.CCR-17-2066; Chen R, 2016, CELL DEATH DIS, V7, DOI 10.1038/cddis.2016.407; Chen ZH, 2013, DIGEST DIS SCI, V58, P2887, DOI 10.1007/s10620-013-2732-8; Cho DH, 2012, ANTICANCER RES, V32, P4091; Choi JH, 2014, GASTROENT RES PRACT, V2014, DOI 10.1155/2014/179586; DeVita VT, 2005, CANC PRINCIPLES PRAC; Du ML, 2014, CARCINOGENESIS, V35, P2723, DOI 10.1093/carcin/bgu189; Fitzmaurice C, 2017, JAMA ONCOL, V3, P524, DOI 10.1001/jamaoncol.2016.5688; Gulhati P, 2009, CLIN CANCER RES, V15, P7207, DOI 10.1158/1078-0432.CCR-09-1249; Hansen TF, 2012, BMC CANCER, V12, DOI 10.1186/1471-2407-12-83; Hur K, 2015, JNCI-J NATL CANCER I, V107, DOI 10.1093/jnci/dju492; Igarashi H, 2015, ANN SURG ONCOL, V22, P2640, DOI 10.1245/s10434-014-4264-7; Itakura E, 2008, MOL BIOL CELL, V19, P5360, DOI 10.1091/mbc.E08-01-0080; Ju J. 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J	Mellor, HR; Harris, AL				Mellor, Howard R.; Harris, Adrian L.			The role of the hypoxia-inducible BH3-only proteins BNIP3 and BNIP3L in cancer	CANCER AND METASTASIS REVIEWS			English	Review						hypoxia; tumor; cell death; BH3; apoptosis; autophagy	AUTOPHAGIC CELL-DEATH; TRANSMEMBRANE DOMAIN; BREAST-CANCER; UP-REGULATION; GENE-EXPRESSION; GXXXG MOTIF; BH3 DOMAIN; IN-SITU; MITOCHONDRIAL; APOPTOSIS	In this review, we summarize current knowledge of the biological functions of the atypical BH3-only proteins BNIP3 and BNIP3L, focusing on the role of these proteins in cancer. Hypoxia increases the expression of BNIP3 through the transcription factor HIF-1, but despite a considerable number of investigations, it has proven difficult to establish a clear role for BNIP3 in the cellular hypoxic response. BNIP3 can induce a form of cell death that shows features of both necrosis and apoptosis, but unusually for a BH3-only protein, death occurs independently of the BH3 domain and is critically dependent on a C-terminal transmembrane domain, which also localizes the protein to the mitochondria. BNIP3 expression does not always result in cell death, suggesting that additional factors may suppress BNIP3 or cooperate with it to induce death. BNIP3 is highly expressed in some tumors, including those of the breast, lung and cervix. However, in colorectal and pancreatic cancers BNIP3 is frequently epigenetically silenced, possibly reflecting different functions for BNIP3 in different tissues. Recent reports have shown that BNIP3 can induce autophagy and there is some evidence to suggest this may represent an emerging role for BH3-only proteins in general. However, the mechanism through which BNIP3 induces autophagy and the cellular consequences of this are yet to be established.	Univ Oxford, John Radcliffe Hosp, Canc Res UK Mol Oncol Labs, Growth Factor Grp, Oxford OX3 9DS, England		Harris, AL (corresponding author), Univ Oxford, John Radcliffe Hosp, Canc Res UK Mol Oncol Labs, Growth Factor Grp, Oxford OX3 9DS, England.	howard.mellor@imm.ox.ac.uk; aharris.lab@cancer.org.uk	Harris, Adrian/ABA-3343-2020	Harris, Adrian/0000-0003-1376-8409			Abe T, 2005, J GASTROENTEROL, V40, P504, DOI 10.1007/s00535-005-1576-1; Akada M, 2005, CLIN CANCER RES, V11, P3094, DOI 10.1158/1078-0432.CCR-04-1785; Bacon AL, 2007, ONCOGENE, V26, P132, DOI 10.1038/sj.onc.1209761; Bandyopadhyay S, 2006, CANCER RES, V66, P5934, DOI 10.1158/0008-5472.CAN-05-3197; Bocharov EV, 2007, J BIOL CHEM, V282, P16256, DOI 10.1074/jbc.M701745200; BOYD JM, 1994, CELL, V79, P341, DOI 10.1016/0092-8674(94)90202-X; Bruick RK, 2000, P NATL ACAD SCI USA, V97, P9082, DOI 10.1073/pnas.97.16.9082; Burton TR, 2006, INT J CANCER, V118, P1660, DOI 10.1002/ijc.21547; Chen G, 1999, J BIOL CHEM, V274, P7, DOI 10.1074/jbc.274.1.7; 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DEC	2007	26	3-4					553	566		10.1007/s10555-007-9080-0			14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	230MC	WOS:000250879600016	17805942				2022-04-25	
J	Matrone, A; Grossi, V; Chiacchiera, F; Fina, E; Cappellari, M; Caringella, AM; Di Naro, E; Loverro, G; Simone, C				Matrone, Antonio; Grossi, Valentina; Chiacchiera, Fulvio; Fina, Emanuela; Cappellari, Marianna; Caringella, Anna Maria; Di Naro, Edoardo; Loverro, Giuseppe; Simone, Cristiano			p38 alpha Is Required for Ovarian Cancer Cell Metabolism and Survival	INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER			English	Article						Ovarian cancer; p38 alpha; HIF1 alpha; AMPK; FoxO3A; Autophagy	POSITRON-EMISSION-TOMOGRAPHY; HYPOXIA; TUMOR; DEATH; AUTOPHAGY; FOXO; PHOSPHORYLATION; TRANSCRIPTION; EXPRESSION; APOPTOSIS	Introduction: Ovarian cancer is highly sensitive to chemotherapy but also shows a high rate of recurrence and drug resistance. These negative outcomes mostly depend on altered apoptotic pathways, making the design of new therapeutic strategies based on the induction of other types of cell death highly desirable. Several lines of research are now addressing cancer-specific features to specifically target tumor cells, thus reducing adverse effects. In this light, a great deal of attention has been devoted to the metabolic reprogramming occurring in cancer cells, which display increased levels of glycolysis compared with their normal counterparts. We recently showed that inhibition of p38 alpha impairs key metabolic functions of colorectal cancer cells, inducing growth arrest, autophagy, and cell death both in vivo and in vitro. These effects are mediated by a switch from hypoxia-inducible factor 1 alpha (HIF1 alpha) to forkhead transcription factor O (Fox)-dependent transcription. Methods: We first characterized p38 expression in OVCAR-3, A2780, and SKOV-3 ovarian cancer cell lines. Then, we treated these cells with the p38 alpha/p38A-specific inhibitor SB202190 and performed a morphological, proliferation, and survival analyses. Finally, we studied HIF1 alpha and FoxO3A expressions and signaling pathways to evaluate their role in SB202190-induced effects. Results: p38 alpha blockade induces the formation of intracellular autophagic vacuoles and reduces growth and viability of ovarian cancer cells. As in colorectal cancer, the underlying molecular mechanism seems to rely on a shift from HIF1 alpha- to FoxO3A-dependent transcription, which is promoted by the activation of the adenosine monophosphate-activated protein kinase pathway. Conclusions: These data corroborate the hypothesis that pharmacological modulation of genes involved in cancer-specific homeostasis, such as p38 alpha, might be exploited to design new therapeutic approaches to cancer treatment.	[Matrone, Antonio; Grossi, Valentina; Chiacchiera, Fulvio; Fina, Emanuela; Cappellari, Marianna; Simone, Cristiano] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Translat Pharmacol, Lab Signal Dependent Transcript, I-66030 Santa Maria Imbaro, Italy; [Caringella, Anna Maria; Di Naro, Edoardo; Loverro, Giuseppe] Univ Bari, Sch Med, Dept Obstet & Gynecol, Bari, Italy		Simone, C (corresponding author), Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Translat Pharmacol, Lab Signal Dependent Transcript, I-66030 Santa Maria Imbaro, Italy.	simone@negrisud.it	GROSSI, Valentina/O-6546-2019; Chiacchiera, Fulvio/ABD-6137-2020; Chiacchiera, Fulvio/K-6740-2016; Grossi, Valentina/K-9821-2016; Simone, Cristiano/K-3452-2018; Fina, Emanuela/E-2828-2017	GROSSI, Valentina/0000-0003-3843-1618; Chiacchiera, Fulvio/0000-0003-3830-2090; Grossi, Valentina/0000-0003-3843-1618; Simone, Cristiano/0000-0002-2628-7658; Fina, Emanuela/0000-0002-9837-4320; di naro, edoardo/0000-0001-7675-7171; loverro, giuseppe/0000-0002-8192-9959	Italian Association for Cancer ResearchFondazione AIRC per la ricerca sul cancro; Progetti di Ricerca Scientifica di Ateneo-es. fin. 2009, Universita degli Studi di Bari	This work was partially supported by a My First Grant (to C. S.) from the Italian Association for Cancer Research and the Progetti di Ricerca Scientifica di Ateneo-es. fin. 2009, Universita degli Studi di Bari (to G. L.).	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J. Gynecol. Cancer	FEB	2010	20	2					203	211		10.1111/IGC.0b013e3181c8ca12			9	Oncology; Obstetrics & Gynecology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Obstetrics & Gynecology	562NT	WOS:000275059300003	20169663				2022-04-25	
S	Vegliante, R; Ciriolo, MR		Litwack, G		Vegliante, Rolando; Ciriolo, Maria R.			Autophagy and Autophagic Cell Death: Uncovering New Mechanisms Whereby Dehydroepiandrosterone Promotes Beneficial Effects on Human Health	DEHYDROEPIANDROSTERONE	Vitamins and Hormones		English	Review; Book Chapter							COLONIC ADENOCARCINOMA CELLS; PREVENTS OXIDATIVE INJURY; GENE-EXPRESSION; SIGNALING PATHWAY; DHEA TREATMENT; CANCER CELLS; BONE-MARROW; AGING BRAIN; APOPTOSIS; PROLIFERATION	Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in human serum and a precursor of sexual hormones. Its levels, which are maximum between the age of 20 and 30, dramatically decline with aging thus raising the question that many pathological conditions typical of the elderly might be associated with the decrement of circulating DHEA. Moreover, since its very early discovery, DHEA and its metabolites have been shown to be active in many pathophysiological contexts, including cardiovascular disease, brain disorders, and cancer. Indeed, treatment with DHEA has beneficial effects for the cure of these and many other pathologies in vitro, in vivo, and in patient studies. However, the molecular mechanisms underlying DHEA effects have been only partially elucidated. Autophagy is a self-digestive process, by which cell homeostasis is maintained, damaged organelles removed, and cell survival assured upon stress stimuli. However, high rate of autophagy is detrimental and leads to a form of programmed cell death known as autophagic cell death (ACD). In this chapter, we describe the process of autophagy and the morphological and biochemical features of ACD. Moreover, we analyze the beneficial effects of DHEA in several pathologies and the molecular mechanisms with particular emphasis on its regulation of cell death processes. Finally, we review data indicating DHEA and structurally related steroid hormones as modulators of both autophagy and ACD, a research field that opens new avenues in the therapeutic use of these compounds.	[Vegliante, Rolando] Hop Civil, Inst Hematol & Immunol, Microenvironm Niche Tumorigenesis & Targeted Ther, MN3T, Strasbourg, France; [Ciriolo, Maria R.] Univ Roma Tor Vergata, Rome, Italy; [Ciriolo, Maria R.] IRCCS San Raffaele La Pisana, Rome, Italy		Ciriolo, MR (corresponding author), Univ Roma Tor Vergata, Rome, Italy.; Ciriolo, MR (corresponding author), IRCCS San Raffaele La Pisana, Rome, Italy.	ciriolo@bio.uniroma2.it					Abounit Kadija, 2012, World J Biol Chem, V3, P1, DOI 10.4331/wjbc.v3.i1.1; Allolio B, 2002, TRENDS ENDOCRIN MET, V13, P288, DOI 10.1016/S1043-2760(02)00617-3; Anagnostopoulou V, 2013, ENDOCRINOLOGY, V154, P2446, DOI 10.1210/en.2012-2249; Aragno M, 2000, DIABETES, V49, P1924, DOI 10.2337/diabetes.49.11.1924; Arnold JT, 2007, PROSTATE, V67, P1152, DOI 10.1002/pros.20585; Azad MB, 2008, AUTOPHAGY, V4, P195, DOI 10.4161/auto.5278; BARRETTCONNOR E, 1986, NEW ENGL J MED, V315, P1519, DOI 10.1056/NEJM198612113152405; Bastianetto S, 1999, MOL BRAIN RES, V66, P35, DOI 10.1016/S0169-328X(99)00002-9; 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Horm.		2018	108						273	307		10.1016/bs.vh.2018.01.006			35	Biochemistry & Molecular Biology; Endocrinology & Metabolism	Book Citation Index – Science (BKCI-S); Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Endocrinology & Metabolism	BL5NS	WOS:000452381500011	30029730				2022-04-25	
J	Song, XX; Lee, DH; Dilly, AK; Lee, YS; Choudry, HA; Kwon, YT; Bartlett, DL; Lee, YJ				Song, Xinxin; Lee, Dae-Hee; Dilly, Ashok-Kumar; Lee, Young-Sun; Choudry, Haroon Asif; Kwon, Yong Tae; Bartlett, David L.; Lee, Yong J.			Crosstalk Between Apoptosis and Autophagy Is Regulated by the Arginylated BiP/Beclin-1/p62 Complex	MOLECULAR CANCER RESEARCH			English	Article							UNFOLDED PROTEIN RESPONSE; BECLIN 1; PERITONEAL CARCINOMATOSIS; CELL-DEATH; ER STRESS; PROTEASOME INHIBITION; SELECTIVE AUTOPHAGY; COLORECTAL-CANCER; MULTIPLE-MYELOMA; MITOMYCIN-C	Emerging evidence demonstrates that autophagy and apoptosis are interconnected and their interplay greatly affects cell death. However, the key regulators in this crosstalk remain elusive. Therefore, the role of N-terminal arginylated BiP (R-BiP)/Beclin-1/p62 complex was examined in the crosstalk between apoptosis and autophagy during combination chemotherapy with mitomycin C and bortezomib using immunoblot, immunoprecipitation, and cellular imaging assays in wild-type (WT) and genetically engineered colorectal cancer cells. In addition, the tumoricidal efficacy of the combinatorial treatment in a nude mouse tumor xenograft model of colorectal cancer was assessed. Bortezomib combined with mitomycin C synergistically induced cytotoxicity and apoptosis rather than autophagy. Mechanistically, this combination inactivated Akt and subsequently induced Beclin-1 (BECN1) dephosphorylation at Ser 234/295. Dephos-phorylation of Beclin-1 resulted in increased cleavage of Beclin-1 and disruption of the R-BiP/Beclin-1/p62 complex, which led to switching autophagy to the synergistic induction of apoptosis. Importantly, the combination significantly suppressed LS174T intraperitoneal xenograft tumor growth, induced Akt inactivation and Beclin-1 cleavage, and decreased autophagy in vivo. Moreover, the tumoricidal efficacy of the combinatorial treatment was less effective, in vitro and in vivo, in HCT116 tumors harboring a Beclin-1 caspase 8 cleavage site mutant knock-in. Implications: This study uncovers that the R-BiP/Beclin-1/p62 complex has an important role in the crosstalk between apoptosis and autophagy. The results also propose how mono-drug resistance can be overcome using potent combinations to improve anticancer therapy.	[Song, Xinxin; Dilly, Ashok-Kumar; Lee, Young-Sun; Choudry, Haroon Asif; Bartlett, David L.; Lee, Yong J.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA; [Lee, Dae-Hee] Korea Univ, Coll Med, Dept Internal Med, Div Med Oncol, Seoul, South Korea; [Lee, Dae-Hee] Korea Univ, Coll Med, Brain Korea Program Biomed Sci 21, Seoul, South Korea; [Kwon, Yong Tae] Seoul Natl Univ, Prot Metab Med Res Ctr, Seoul, South Korea; [Lee, Dae-Hee] Seoul Natl Univ, Dept Biomed Sci, Coll Med, Seoul, South Korea		Lee, YJ (corresponding author), Univ Pittsburgh, Dept Surg, Hillman Canc Ctr, 5117 Ctr Ave,Room 1-46C, Pittsburgh, PA 15213 USA.	leeyj@upmc.edu			NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA205267, CA212125]; National Research Foundation of KoreaNational Research Foundation of Korea [NRF-2013R1A2A2A01014170, NRF-2016R1A2B3011389]; Nobel Laureates Invitation Program of Seoul National University;  [P30CA047904]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R03CA205267, P30CA047904, R03CA212125] Funding Source: NIH RePORTER	This work was supported by the following grants: NCI grants CA205267 and CA212125 to Y.J. Lee; National Research Foundation of Korea Program grants NRF-2013R1A2A2A01014170 and NRF-2016R1A2B3011389 to Y.T. Kwon; and Nobel Laureates Invitation Program of Seoul National University to Y.T. Kwon. This project used the UPCI Core Facility and was supported in part by award P30CA047904 to the University of Pittsburgh Cancer Institute.	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Cancer Res.	JUL	2018	16	7					1077	1091		10.1158/1541-7786.MCR-17-0685			15	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	GL6EC	WOS:000437272500002	29669822	Green Accepted, Bronze			2022-04-25	
J	Koyuncu, I; Gonel, A; Temiz, E; Karaogul, E; Uyar, Z				Koyuncu, Ismail; Gonel, Ataman; Temiz, Ebru; Karaogul, Eyyup; Uyar, Zafer			Pistachio Green Hull Extract Induces Apoptosis through Multiple Signaling Pathways by Causing Oxidative Stress on Colon Cancer Cells	ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY			English	Article						Apoptosis; cytotoxicity; colorectal cancer; anti-cancer agent; oxidative stress; phenolic compounds		Background: Pistachio is considered to be one of the fifty foods with the highest antioxidant effect. However, the anticancer effect mechanisms of this plant extracts are unknown. Objective: The aim of this study was to investigate the anticancer effect of different extracts from the green hull of pistachio. Methods: The cytotoxic effects of different solvent extracts on cancer and normal cells were examined by cell viability assay and flow cytometric analysis. The levels of the apoptotic gene and protein were investigated by Western Blot and ELISA, and qPCR. The intracellular free radical exchange was determined by oxidative and nitric oxide analyses. DNA damage level was measured by the 8-OHdG test. Phenolic and free fatty acid components were examined by LC-MS/MS and GC-MS, respectively. Results: It was determined that the n-hexane fraction showed a higher cytotoxic effect on cancer cells. Oxidative and cell cycle analyses indicated that the n-hexane fraction arrested cell cycle of HT-29 at the sub-G(1) phase by increasing DNA damage through oxidative stress. In addition, gene expression analysis of the HT-29 treated with the n-hexane fraction indicated that apoptotic and autophagic gene expressions were significantly upregulated. LC-MS/MS analysis of the n-hexane fraction revealed the presence of 15 phenolic compounds, containing mainly gallic acid and catechin hydrate, and GC-MS analysis determined the presence of the following fatty acids: 9-octadecenoic acid, 9,12-octadecadienoic acid and hexadecenoic acid. Conclusion: Based on these grounds, we suggest that the n-hexane fraction of pistachio green hull damages DNA, arrests the cell cycle at the G(1) subphase, and induces apoptosis through oxidative pathways in colon cancer.	[Koyuncu, Ismail; Gonel, Ataman; Temiz, Ebru] Harran Univ, Med Fac, Dept Med Biochem, Sanliurfa, Turkey; [Karaogul, Eyyup] Harran Univ, Engn Fac, Food Sci & Technol, Sanliurfa, Turkey; [Uyar, Zafer] Harran Univ, Sci Fac, Dept Chem, Sanliurfa, Turkey		Koyuncu, I (corresponding author), Harran Univ, Med Fac, Dept Med Biochem, Sanliurfa, Turkey.	ismailkoyuncu1@gmail.com	Uyar, Zafer/AAF-5391-2021; Temiz, Ebru/ABF-6573-2021	Uyar, Zafer/0000-0002-6310-8823; 	HUBAK department of Harran University [15057]; GAP institution, Turkey [19001]	This research was supported by the HUBAK department of Harran University (Project number: 15057) and GAP institution (Grand number: 19001) , Turkey.	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Chem.		2021	21	6					725	737		10.2174/1871520620999200730155524			13	Oncology; Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	RB0XJ	WOS:000631840600006	32748756				2022-04-25	
J	Liao, D; Li, T; Ye, CG; Zeng, LY; Li, HH; Pu, XX; Ding, CC; He, ZW; Huang, GL				Liao, Dan; Li, Tong; Ye, Caiguo; Zeng, Liuyan; Li, Huahui; Pu, Xingxiang; Ding, Congcong; He, Zhiwei; Huang, Guo-Liang			miR-221 inhibits autophagy and targets TP53INP1 in colorectal cancer cells	EXPERIMENTAL AND THERAPEUTIC MEDICINE			English	Article						autophagy; colorectal cancer; miR-221; tumor protein 53-induced nuclear protein 1	HEPATOCELLULAR-CARCINOMA; PROMOTES AUTOPHAGY; MICRORNA; DEATH; RADIOSENSITIVITY; MARKER; LC3	Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer-associated mortalities worldwide. MicroRNAs (miRNAs/miRs) serve important roles in tumor development, progression and metastasis. miR-221 has been reported to modulate proliferation, apoptosis, cell cycle distribution and cell migration in a variety of cancers. However, the function of miR-221 in the autophagy of cancer is unclear. In the present study, the role of miR-221 in the autophagy of CRC cells was investigated and its associated target was identified. Survival analysis using The Cancer Genome Atlas data suggested that a higher expression of miR-221 was associated with poor survival in patients with CRC. A Cell Counting kit-8 assay revealed that miR-221 promoted CRC cell proliferation. Autophagy flux analyzed by microtubule-associated protein 1 light chain 3 (LC3) turnover indicated that miR-221 reduced autophagy in CRC cells using different protease inhibitors (E64d and pepstatin A; Bafilomycin A1) in nutrient-rich medium or under starvation conditions. Tumor protein 53-induced nuclear protein 1 (TP53INP1) was identified as a potential novel target of miR-221 by bioinformative prediction. The protein expression of TP53INP1 was inversely regulated by miR-221 in CRC cells. Furthermore, luciferase activity assays were performed and indicated that miR-221 may regulate the luciferase activity of wild-type TP53INP1 without interfering with the activity of mutant TP53INP1. These data suggested that miR-221 may promote the cell proliferation of CRC via the inhibition of autophagy and targeted TP53INP1.	[Liao, Dan; Li, Tong; Ye, Caiguo; Li, Huahui; Ding, Congcong; He, Zhiwei; Huang, Guo-Liang] Guangdong Med Univ, Guangdong Prov Key Lab Med Mol Diagnost, Key Lab Epigenet Dongguan City, China Amer Canc Res Inst,Dongguan Sci Res Ctr, Dongguan 523808, Guangdong, Peoples R China; [Liao, Dan] Southern Med Univ, Dept Gynaecol & Obstet, Dongguan Peoples Hosp 3, Affiliated Dongguan Shilong Peoples Hosp, Dongguan 523326, Guangdong, Peoples R China; [Zeng, Liuyan] Guangdong Med Univ, Affiliated Hosp, Dept Hlth Management Ctr, Zhanjiang 524001, Guangdong, Peoples R China; [Pu, Xingxiang] Cent South Univ, Dept Chest Internal Med 2, Hunan Canc Hosp, Affiliated Canc Hosp,Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China		He, ZW; Huang, GL (corresponding author), Guangdong Med Univ, China Amer Canc Res Inst, Dongguan Sci Res Ctr, 1 Xincheng Rd, Dongguan 523808, Guangdong, Peoples R China.	zhiweihe688@yahoo.com; huangguoliang@gdmu.edu.cn	Huang, Guoliang/H-1625-2011	Huang, Guoliang/0000-0002-8902-8100	Science and Technology Planning Project of Guangdong Province [2013B021800070]; Training Plan for Outstanding Young Teachers in Higher Education Institutions of Guangdong Province [YQ201403/YQ2014086]; Hunan Provincial Natural Science Foundation of ChinaNatural Science Foundation of Hunan Province [2015jj6066]; Project of Hunan Provincial Department of Health [B2012-095]	This study was supported by the Science and Technology Planning Project of Guangdong Province (grant no. 2013B021800070), the Training Plan for Outstanding Young Teachers in Higher Education Institutions of Guangdong Province (grant no. YQ201403/YQ2014086), the Hunan Provincial Natural Science Foundation of China (grant no. 2015jj6066), and the Project of Hunan Provincial Department of Health (grant no. B2012-095).	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Ther. Med.	FEB	2018	15	2					1712	1717		10.3892/etm.2017.5522			6	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	FT5VP	WOS:000423221600076	29434757	Green Published, gold			2022-04-25	
J	Wang, JG; Zhang, CJ; Zhang, JB; He, YK; Lee, YM; Chen, SB; Lim, TK; Ng, SK; Shen, HM; Lin, QS				Wang, Jigang; Zhang, Chong-Jing; Zhang, Jianbin; He, Yingke; Lee, Yew Mun; Chen, Songbi; Lim, Teck Kwang; Ng, Shukie; Shen, Han-Ming; Lin, Qingsong			Mapping sites of aspirin-induced acetylations in live cells by quantitative acid-cleavable activity-based protein profiling (QA-ABPP)	SCIENTIFIC REPORTS			English	Article							CHEMICAL PROTEOMICS APPROACH; MULTIPLE CELLULAR-PROTEINS; ACTIVITY-BASED PROBES; COLON-CANCER CELLS; COLORECTAL-CANCER; TARGET IDENTIFICATION; AUTOPHAGY; MTOR; MOLECULES; STRATEGY	Target-identification and understanding of mechanism-of-action (MOA) are challenging for development of small-molecule probes and their application in biology and drug discovery. For example, although aspirin has been widely used for more than 100 years, its molecular targets have not been fully characterized. To cope with this challenge, we developed a novel technique called quantitative acid-cleavable activity-based protein profiling (QA-ABPP) with combination of the following two parts: (i) activity-based protein profiling (ABPP) and iTRAQ (TM) quantitative proteomics for identification of target proteins and (ii) acid-cleavable linker-based ABPP for identification of peptides with specific binding sites. It is known that reaction of aspirin with its target proteins leads to acetylation. We thus applied the above technique using aspirin-based probes in human cancer HCT116 cells. We identified 1110 target proteins and 2775 peptides with exact acetylation sites. By correlating these two sets of data, 523 proteins were identified as targets of aspirin. We used various biological assays to validate the effects of aspirin on inhibition of protein synthesis and induction of autophagy which were elicited from the pathway analysis of Aspirin target profile. This technique is widely applicable for target identification in the field of drug discovery and biology, especially for the covalent drugs.	[Wang, Jigang; Lee, Yew Mun; Lim, Teck Kwang; Lin, Qingsong] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore; [Zhang, Chong-Jing; Chen, Songbi] Chinese Acad Trop Agr Sci, Trop Crops Genet Resources Inst, Danzhou, Hainan, Peoples R China; [Zhang, Jianbin; Ng, Shukie; Shen, Han-Ming] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117597, Singapore; [He, Yingke] Singapore Gen Hosp, Dept Anaesthesiol, Singapore 169608, Singapore		Shen, HM (corresponding author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Block MD9,2 Med Dr, Singapore 117597, Singapore.	han-ming_shen@nuhs.edu.sg; dbslinqs@nus.edu.sg	SHEN, Han-Ming/B-5942-2011; Lin, Qingsong/H-9794-2012; Zhang, Chong-Jing/AAO-5782-2021; Lee, Yew Mun/G-8891-2017	SHEN, Han-Ming/0000-0001-7369-5227; Lin, Qingsong/0000-0001-9117-8514; Lee, Yew Mun/0000-0002-8360-7689; Zhang, Chong-Jing/0000-0002-3396-9999	NUS research scholarshipNational University of Singapore; Initial Fund of High-level Creative Talents in Hainan Province	J.W. and J.Z. were supported by NUS research scholarship. We would like to thank Prof. Kim Chu-Young for helpful discussions and proofreading of this manuscript. We acknowledge the financial support from the Initial Fund of High-level Creative Talents in Hainan Province (Chen Songbi).	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J	Maioli, E; Torricelli, C; Valacchi, G				Maioli, E.; Torricelli, C.; Valacchi, G.			Rottlerin and Cancer: Novel Evidence and Mechanisms	SCIENTIFIC WORLD JOURNAL			English	Review							PROTEIN-KINASE-C; NF-KAPPA-B; ENDOPLASMIC-RETICULUM STRESS; DELTA-INDEPENDENT PATHWAY; MALIGNANT GLIOMA-CELLS; COLON-CARCINOMA CELLS; NECROSIS-FACTOR-ALPHA; PKC-DELTA; INDUCED APOPTOSIS; BREAST-CANCER	Because cancers are caused by deregulation of hundreds of genes, an ideal anticancer agent should target multiple gene products or signaling pathways simultaneously. Recently, extensive research has addressed the chemotherapeutic potential of plant-derived compounds. Among the ever-increasing list of naturally occurring anticancer agents, Rottlerin appears to have great potentiality for being used in chemotherapy because it affects several cell machineries involved in survival, apoptosis, autophagy, and invasion. The underlying mechanisms that have been described are diverse, and the final, cell-specific, Rottlerin outcome appears to result from a combination of signaling pathways at multiple levels. This paper seeks to summarize the multifocal signal modulatory properties of Rottlerin, which merit to be further exploited for successful prevention and treatment of cancer.	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World J.		2012									350826	10.1100/2012/350826			11	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	916FT	WOS:000302085700001	22272173	Green Published, gold, Green Submitted			2022-04-25	
J	Lin, BW; Gong, CC; Song, HF; Cui, YY				Lin, Bo-Wen; Gong, Cheng-Chen; Song, Hai-Fei; Cui, Ying-Yu			Effects of anthocyanins on the prevention and treatment of cancer	BRITISH JOURNAL OF PHARMACOLOGY			English	Review							MASSONIANA BARK EXTRACT; NF-KAPPA-B; RECEPTOR TYROSINE KINASES; OXIDATIVE STRESS MARKERS; BLACK RICE ANTHOCYANINS; SUPPRESS TUMOR-GROWTH; CELLS IN-VITRO; CONCISE GUIDE; COLON-CANCER; BLUEBERRY ANTHOCYANINS	Anthocyanins are a class of water-soluble flavonoids, which show a range of pharmacological effects, such as prevention of cardiovascular disease, obesity control and antitumour activity. Their potential antitumour effects are reported to be based on a wide variety of biological activities including antioxidant; anti-inflammation; anti-mutagenesis; induction of differentiation; inhibiting proliferation by modulating signal transduction pathways, inducing cell cycle arrest and stimulating apoptosis or autophagy of cancer cells; anti-invasion; anti-metastasis; reversing drug resistance of cancer cells and increasing their sensitivity to chemotherapy. In this review, the latest progress on the anticancer activities of anthocyanins and the underlying molecular mechanisms is summarized using data from basic research in vitro and in vivo, from clinical trials and taking into account theory and practice.	[Cui, Ying-Yu] Tongji Univ, Minist Educ, Key Lab Arrhythmias, Shanghai, Peoples R China; [Cui, Ying-Yu] Tongji Univ, Inst Med Genet, Sch Med, Shanghai, Peoples R China		Cui, YY (corresponding author), Tongji Univ, Sch Med, Dept Regenerat Med, Shanghai 200092, Peoples R China.	yycui@tongji.edu.cn	Andrew, Ruth/C-2727-2008; Cui, Ying-Yu/G-6386-2011	Andrew, Ruth/0000-0002-6916-2994; Cui, Ying-Yu/0000-0002-6324-0795	University Students Innovation Training Program of Shanghai Municipal Government [201610247134]; Yangfan Project of Tongji University School of Medicine [2012YF05]	This work was supported by the University Students Innovation Training Program of Shanghai Municipal Government [grant number 201610247134 to HF Song] and the Yangfan Project of Tongji University School of Medicine [grant number 2012YF05 to YY Cui]. The authors thank the staff of the Key Laboratory of Arrhythmias, Ministry of Education (Tongji University) for their technical assistance. We also thank the editor and reviewers for their comments and suggestions, which have improved this review considerably.	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J	Lee, M; Choi, H; Kim, KS; Kim, DH; Kim, CH; Lee, YC				Lee, Miri; Choi, Hyunju; Kim, Kyoung-Sook; Kim, Dong-Hyun; Kim, Cheorl-Ho; Lee, Young-Choon			Curcumin Downregulates Human GM3 Synthase (hST3Gal V) Gene Expression with Autophagy Induction in Human Colon Carcinoma HCT116 Cells	EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE			English	Article							TRANSCRIPTIONAL REGULATION; VALPROIC ACID; DIFFERENTIATION; GANGLIOSIDES; GLYCOSPHINGOLIPIDS; INVOLVEMENT; CANCER; ORGANIZATION; ACTIVATION; DEATH	Our recent report showed that curcumin, polyphenolic compound isolated from the herb Curcuma longa, upregulated the gene expression of human GD3 synthase (hST8Sia I) responsible for ganglioside GD3 synthesis with autophagy induction in human lung adenocarcinoma A549 cells. In this study, on the contrary to this finding, we demonstrated that curcumin downregulated the gene expression of human GM3 synthase (hST3Gal V) catalyzing ganglioside GM3 synthesis with autophagy induction in human colon carcinoma HCT116 cells. To clarify the mechanism leading to the downregulation of hST3Gal V gene expression in curcumin-treated HCT116 cells, we analyzed the curcumin-inducible promoter of the hST3Gal V gene by luciferase reporter assays. Promoter deletion analysis demonstrated that the -177 to -83 region, which includes putative binding sites for transcription factors NFY, CREB/ATF, SP1, EGR3, and MZF1, acts as the curcumin-responsive promoter of the hST3Gal V gene. Site-directed mutagenesis and chromatin immunoprecipitation analysis demonstrated that the CREB/ATF binding site at -143 is pivotal for curcumin-induced downregulation of hST3Gal V gene in HCT116 cells. The transcriptional activation of hST3Gal V in HCT116 cells was significantly repressed by an inhibitor of AMP-activated protein kinase (AMPK). These results suggest that AMPK signal pathway mediates hST3Gal V gene expression in HCT116 cells.	[Lee, Miri; Kim, Kyoung-Sook; Kim, Dong-Hyun; Lee, Young-Choon] Dong A Univ, Coll Hlth Sci, Dept Med Biotechnol, Busan 49315, South Korea; [Choi, Hyunju; Kim, Cheorl-Ho] Sungkyunkwan Univ, Dept Biol Sci, Mol & Cellular Glycobiol Unit, Kyunggi Do 16419, South Korea		Lee, YC (corresponding author), Dong A Univ, Coll Hlth Sci, Dept Med Biotechnol, Busan 49315, South Korea.; Kim, CH (corresponding author), Sungkyunkwan Univ, Dept Biol Sci, Mol & Cellular Glycobiol Unit, Kyunggi Do 16419, South Korea.	chkimbio@skku.edu; yclee@dau.ac.kr	Kim, Cheorl-Ho/T-6753-2019	Kim, Cheorl-Ho/0000-0002-6323-0714	Dong-A University	This work was supported by the Dong-A University research fund.	Bektas M, 2003, GLYCOCONJUGATE J, V20, P39, DOI 10.1023/B:GLYC.0000016741.88476.8b; Choi HJ, 2004, BIOCHEM BIOPH RES CO, V313, P142, DOI 10.1016/j.bbrc.2003.11.103; Choi HJ, 2003, FEBS LETT, V555, P204, DOI 10.1016/S0014-5793(03)01227-4; Chung TW, 2005, GLYCOBIOLOGY, V15, P233, DOI 10.1093/glycob/cwh156; D'Angelo G, 2013, FEBS J, V280, P6338, DOI 10.1111/febs.12559; Ghidoni R, 1996, EUR J BIOCHEM, V237, P454, DOI 10.1111/j.1432-1033.1996.0454k.x; Hakomori S, 2003, CURR OPIN HEMATOL, V10, P16, DOI 10.1097/00062752-200301000-00004; Hwang J, 2010, J NEUROIMMUNOL, V226, P66, DOI 10.1016/j.jneuroim.2010.05.037; Hwang J, 2010, BRIT J PHARMACOL, V159, P586, DOI 10.1111/j.1476-5381.2009.00563.x; Kim SW, 2002, BBA-GENE STRUCT EXPR, V1578, P84, DOI 10.1016/S0167-4781(02)00505-5; Kwon HY, 2008, ACTA PHARMACOL SIN, V29, P999, DOI 10.1111/j.1745-7254.2008.00847.x; Lee M, 2018, INT J MOL SCI, V19, DOI 10.3390/ijms19071943; Lee YJ, 2011, KOREAN J PHYSIOL PHA, V15, P1, DOI 10.4196/kjpp.2011.15.1.1; Maccioni HJF, 2007, J NEUROCHEM, V103, P81, DOI 10.1111/j.1471-4159.2007.04717.x; Matarrese P, 2014, AUTOPHAGY, V10, P750, DOI 10.4161/auto.27959; Mosieniak G, 2012, MECH AGEING DEV, V133, P444, DOI 10.1016/j.mad.2012.05.004; Pan W, 2008, ONCOL REP, V20, P1553, DOI 10.3892/or_00000179; Puissant A, 2012, AM J CANCER RES, V2, P397; Schengrund CL, 2015, TRENDS BIOCHEM SCI, V40, P397, DOI 10.1016/j.tibs.2015.03.007; Song N, 2011, BMB REP, V44, P405, DOI 10.5483/BMBRep.2011.44.6.405; Sonnino S, 2010, ADV EXP MED BIOL, V688, P165; Tong WH, 2016, ONCOL LETT, V12, P4139, DOI 10.3892/ol.2016.5148; Vyas KA, 2001, BIOL CHEM, V382, P241, DOI 10.1515/BC.2001.031; Yoon HK, 2016, INT J MOL SCI, V17, DOI 10.3390/ijms17010035; Zhang XJ, 2013, ACTA PHARMACOL SIN, V34, P595, DOI 10.1038/aps.2012.184	25	2	2	0	0	HINDAWI LTD	LONDON	ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND	1741-427X	1741-4288		EVID-BASED COMPL ALT	Evid.-based Complement Altern. Med.		2018	2018								6746412	10.1155/2018/6746412			7	Integrative & Complementary Medicine	Science Citation Index Expanded (SCI-EXPANDED)	Integrative & Complementary Medicine	HB5XC	WOS:000451135900001	30534177	Green Published, Green Submitted, gold			2022-04-25	
J	Tan, H; Li, X; Yang, WH; Kang, Y				Tan, Hao; Li, Xiang; Yang, Wei-Han; Kang, Yong			A flavone, Wogonin from Scutellaria baicalensis inhibits the proliferation of human colorectal cancer cells by inducing of autophagy, apoptosis and G2/M cell cycle arrest via modulating the PI3K/AKT and STAT3 signalling pathways	JOURNAL OF BUON			English	Article						wogonin; colorectal cancer; autophagy; apoptosis	NATURAL-PRODUCTS; ACTIVATION	Purpose: The purpose of this study was to examine the anticancer effects of a flavone from Scutellaria baicalensis wogonin against a panel of colorectal cancer cells. Methods: The SW1417, SW48, DLD-1, HCT-I5, LS-180 and CCD-18Co cell lines were used for the evaluation of the anticancer effects of wogonin. WST-1 and colony formation assays were used for cell viability assessment. Cell cycle analysis was assessed by flow cytometry. Autophagy was detected by electron microscopy. Apoptosis was detected by acridine orange (AO)/ethidium bromide (EB) staining. Cell protein expression was checked by western blotting. Results: The cytotoxic effects of wogonin were comparatively negligible against the normal CCD-18Co cells with an IC50 of >100 mu M. Investigation of the mechanism of action revealed that wogonin exerts growth inhibitory effects on the SW48 colorectal cancer cells by autophagic and apoptotic cell death. This was also accompanied with upregulation of autophagic proteins such as LC3II and Beclin 1 as well as the apoptotic proteins such as caspase 3, 8 and 9 and Bax expressions. Wogonin also induced arrest of the SW48 cells at the G2/M check point of the cell cycle. In addition, wogonin could also inhibit the PI3K/AKT and STAT3 signal transduction pathways. Conclusion: These results suggest that wogonin exerts potent anticancer effects on colorectal cancer cells and may prove essential in the management of colorectal cancer.	[Tan, Hao; Li, Xiang; Yang, Wei-Han; Kang, Yong] Shanxi Prov Acad Tradit Chinese Med, Bing Zhouxi St 46, Taiyuan 030012, Shanxi, Peoples R China		Kang, Y (corresponding author), Shanxi Prov Acad Tradit Chinese Med, Bing Zhouxi St 46, Taiyuan 030012, Shanxi, Peoples R China.	KNanceylse@yahoo.com					Aran V, 2016, CLIN COLORECTAL CANC, V15, P195, DOI 10.1016/j.clcc.2016.02.008; Arnold M, 2017, GUT, V66, P683, DOI 10.1136/gutjnl-2015-310912; Huynh DL, 2017, BMC COMPLEM ALTERN M, V17, DOI 10.1186/s12906-017-1788-y; Fu P, 2015, CELL MOL BIOL, V61, P123; Gao JC, 2009, CANCER SCI, V100, P389, DOI 10.1111/j.1349-7006.2008.01053.x; Go JH, 2018, INT J MOL MED, V42, P1899, DOI 10.3892/ijmm.2018.3776; Guinney J, 2015, NAT MED, V21, P1350, DOI 10.1038/nm.3967; Harvey AL, 2015, NAT REV DRUG DISCOV, V14, P111, DOI 10.1038/nrd4510; Huang KF, 2012, INT IMMUNOPHARMACOL, V12, P334, DOI 10.1016/j.intimp.2011.12.004; Khan NM, 2017, FREE RADICAL BIO MED, V106, P288, DOI 10.1016/j.freeradbiomed.2017.02.041; Kim MS, 2013, CELL BIOL TOXICOL, V29, P259, DOI 10.1007/s10565-013-9251-4; Koff JL, 2015, INT J MOL SCI, V16, P2942, DOI 10.3390/ijms16022942; Lee DH, 2012, CELL SIGNAL, V24, P2216, DOI 10.1016/j.cellsig.2012.07.019; Li HB, 2005, J CHROMATOGR A, V1074, P107, DOI 10.1016/j.chroma.2005.03.088; NAKAMURA N, 1990, RADIAT RES, V123, P224, DOI 10.2307/3577549; Newman DJ, 2016, J NAT PROD, V79, P629, DOI 10.1021/acs.jnatprod.5b01055; Patridge E, 2016, DRUG DISCOV TODAY, V21, P204, DOI 10.1016/j.drudis.2015.01.009; Romano B, 2013, PHYTOTHER RES, V27, P1588, DOI 10.1002/ptr.5023; Saleem M, 2018, ANTI-CANCER AGENT ME, V18, P1650, DOI 10.2174/1871520618666180105161136; Siegel R, 2014, CA-CANCER J CLIN, V64, P104, DOI 10.3322/caac.21220; Van Cutsem E, 2016, ANN ONCOL, V27, P1386, DOI 10.1093/annonc/mdw235; White E, 2015, J CLIN INVEST, V125, P42, DOI 10.1172/JCI73941; Yang L, 2009, BIOCHEM CELL BIOL, V87, P933, DOI [10.1139/O09-060, 10.1139/o09-060]	23	19	21	1	3	IMPRIMATUR PUBLICATIONS	ATHENS	30 DEM POLIORKETES ST, ATHENS, 136 76, GREECE	1107-0625	2241-6293		J BUON	J. BUON	MAY-JUN	2019	24	3					1143	1149					7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	ID6CK	WOS:000471764000038	31424673				2022-04-25	
J	Zhang, JX; Tan, P; Guo, L; Gong, J; Ma, JJ; Li, J; Lee, M; Fang, SH; Jing, J; Johnson, G; Sun, DQ; Cao, WM; Dashwood, R; Han, L; Zhou, YB; Dong, WG; Huang, Y				Zhang, Jixiang; Tan, Peng; Guo, Lei; Gong, Jing; Ma, Jingjing; Li, Jia; Lee, Minjung; Fang, Shaohai; Jing, Ji; Johnson, Gavin; Sun, Deqiang; Cao, Wen-ming; Dashwood, Roderick; Han, Leng; Zhou, Yubin; Dong, Wei-Guo; Huang, Yun			p53-dependent autophagic degradation of TET2 modulates cancer therapeutic resistance	ONCOGENE			English	Article							DNA-DAMAGE; STEM-CELLS; P53; 5-HYDROXYMETHYLCYTOSINE; 5-METHYLCYTOSINE; ANTICANCER; MUTATIONS; MOUSE; REPLICATION; METHYLATION	Tumor cells with p53 inactivation frequently exhibit chemotherapy resistance, which poses a long-standing challenge to cancer treatment. Here we unveiled a previously unrecognized role of TET2 in mediating p53-loss induced chemotherapy resistance in colon cancer. Deletion of TET2 in p53-null colon cancer cells enhanced DNA damage and restored chemotherapy sensitivity. By taking a two-pronged approach that combined pharmacological inhibition with genetic depletion, we discovered that p53 destabilized TET2 at the protein level by promoting its autophagic degradation. At the molecular level, we further revealed a physical association between TET2 and p53 that facilitated the nucleoplasmic shuttling of TET2, as well as its recruitment to the autophagosome for degradation. Our study has unveiled a functional interplay between TET2 and p53 during anti-cancer therapy. Our findings establish the rationale for targeting TET2 to overcome chemotherapy resistance associated with mutant p53 tumors.	[Zhang, Jixiang; Guo, Lei; Li, Jia; Lee, Minjung; Fang, Shaohai; Johnson, Gavin; Sun, Deqiang; Dashwood, Roderick; Huang, Yun] Texas A&M Univ, Ctr Epigenet & Dis Prevent, Inst Biosci & Technol, Houston, TX 77030 USA; [Zhang, Jixiang; Ma, Jingjing; Dong, Wei-Guo] Wuhan Univ, Dept Gastroenterol, Renmin Hosp, Wuhan 430060, Hubei, Peoples R China; [Tan, Peng; Guo, Lei; Jing, Ji; Zhou, Yubin] Texas A&M Univ, Inst Biosci & Technol, Ctr Translat Canc Res, Houston, TX 77030 USA; [Gong, Jing; Han, Leng] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Biochem & Mol Biol, Houston, TX 77030 USA; [Cao, Wen-ming] Zhejiang Canc Hosp, Dept Breast Med Oncol, Hangzhou 310022, Zhejiang, Peoples R China; [Dashwood, Roderick; Huang, Yun] Texas A&M Univ, Coll Med, Dept Mol & Cellular Med, College Stn, TX 77843 USA; [Zhou, Yubin] Texas A&M Univ, Coll Med, Dept Med Physiol, Temple, TX 76504 USA		Huang, Y (corresponding author), Texas A&M Univ, Ctr Epigenet & Dis Prevent, Inst Biosci & Technol, Houston, TX 77030 USA.; Dong, WG (corresponding author), Wuhan Univ, Dept Gastroenterol, Renmin Hosp, Wuhan 430060, Hubei, Peoples R China.; Zhou, YB (corresponding author), Texas A&M Univ, Inst Biosci & Technol, Ctr Translat Canc Res, Houston, TX 77030 USA.; Huang, Y (corresponding author), Texas A&M Univ, Coll Med, Dept Mol & Cellular Med, College Stn, TX 77843 USA.; Zhou, YB (corresponding author), Texas A&M Univ, Coll Med, Dept Med Physiol, Temple, TX 76504 USA.	yzhou@ibt.tamhsc.edu; dwg@whu.edu.cn; yun.huang@ibt.tamhsc.edu	Zhou, Yubin/D-4748-2011; Dashwood, Roderick/AAF-2025-2020; Tan, Peng/ABD-8190-2020	Zhou, Yubin/0000-0001-7962-0517; Cao, Wen-Ming/0000-0002-5644-3156; Tan, Peng/0000-0001-6992-9000; sun, deqiang/0000-0002-5806-7289; Fang, Shaohai/0000-0003-3940-9586	Cancer Prevention and Research Institute of Texas [RR140053, RP170660, RR150085]; American Heart AssociationAmerican Heart Association [16IRG27250155]; John S. Dunn Foundation; Center for Translational Environmental Health Research (CTEHR); National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01HL134780, R01GM112003]; Welch FoundationThe Welch Foundation [BE-1913]; American Cancer SocietyAmerican Cancer Society [RSG-18-043-01-LIB, RSG-16-215-01-TBE]; Texas AM University; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL134780] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM112003] Funding Source: NIH RePORTER	This work was supported by grants from Cancer Prevention and Research Institute of Texas (RR140053 to YH, to RP170660 to YZ, RR150085 to LH), the Innovation Award from American Heart Association (16IRG27250155 to YH), the John S. Dunn Foundation Collaborative Research Award (to YH), the Center for Translational Environmental Health Research (CTEHR) Seed Grant to YH, the National Institute of Health grants (R01HL134780 to YH, R01GM112003 to YZ), the Welch Foundation (BE-1913 to YZ), the American Cancer Society (RSG-18-043-01-LIB to YH, RSG-16-215-01-TBE to YZ), and by an allocation from the Texas A&M University start-up funds (YH).	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J	Li, TY; Liu, DN; Lei, X; Jiang, QG				Li, Taiyuan; Liu, Dongning; Lei, Xiong; Jiang, Qunguang			Par3L enhances colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						Par3L; CRISPR/Cas; Colorectal cancer; AMPIC pathway; Lkb1	HEPATOCELLULAR-CARCINOMA; POOR-PROGNOSIS; LKB1; EXPRESSION; AMPK; METASTASIS; METABOLISM; AUTOPHAGY; PAR-3	Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells. Consistent with previous studies, we showed that Par3L interacts with a tumor suppressor protein liver kinase B1 (Lkb1). Moreover, Par3L depletion resulted in abnormal activation of Lkb1 /AMPKsignaling cascade. Knockdown of Lkb1 in these cells could significantly reduce AMPK activity and partially rescue cell death caused by Par3L knockdown. Furthermore, we showed that Par3L KO cells were more sensitive to chemotherapies and irradiation. Together, these results suggest that Par3L is essential for colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway, and is a putative therapeutic target for CRC. (C) 2016 Elsevier Inc. All rights reserved.	[Li, Taiyuan; Liu, Dongning; Lei, Xiong; Jiang, Qunguang] Nanchang Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Nanchang, Jiangxi, Peoples R China		Jiang, QG (corresponding author), Nanchang Univ, Hosp Nanchang 1, 17 Yongwai St, Nanchang 330006, Jiangxi, Peoples R China.	JiangQG168@gmail.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81560397]	This work was supported by the National Natural Science Foundation of China (81560397).	Bouchekioua-Bouzaghou K, 2014, INT J CANCER, V135, P1307, DOI 10.1002/ijc.28781; Dagher J, 2014, HUM PATHOL, V45, P1639, DOI 10.1016/j.humpath.2014.03.018; Denison FC, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0028306; Dupuy F, 2013, CANCER METAB, V1, DOI 10.1186/2049-3002-1-18; Huang YH, 2013, ASIAN PAC J CANCER P, V14, P1985, DOI 10.7314/APJCP.2013.14.3.1985; Huo YL, 2014, NAT CELL BIOL, V16, P526, DOI 10.1038/ncb2969; Jan YJ, 2013, INT J MOL SCI, V14, P1684, DOI 10.3390/ijms14011684; Kim YW, 2009, FREE RADICAL BIO MED, V47, P1082, DOI 10.1016/j.freeradbiomed.2009.07.018; Law BYK, 2016, ONCOTARGET, V7, P8090, DOI 10.18632/oncotarget.6980; Lu JL, 2015, MED SCI MONITOR, V21, P3722, DOI 10.12659/MSM.894847; McCaffrey LM, 2012, CANCER CELL, V22, P601, DOI 10.1016/j.ccr.2012.10.003; Mihaylova MM, 2011, NAT CELL BIOL, V13, P1016, DOI 10.1038/ncb2329; Ran FA, 2013, NAT PROTOC, V8, P2281, DOI 10.1038/nprot.2013.143; Shackelford DB, 2013, CANCER CELL, V23, P143, DOI 10.1016/j.ccr.2012.12.008; Shen Z, 2002, CLIN CANCER RES, V8, P2085; Thapalia BA, 2016, AM J TRANSL RES, V8, P3251; Xue B, 2013, NAT CELL BIOL, V15, P189, DOI 10.1038/ncb2663; Yang JY, 2015, SCI REP-UK, V5, DOI 10.1038/srep10575	18	10	11	1	15	ACADEMIC PRESS INC ELSEVIER SCIENCE	SAN DIEGO	525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA	0006-291X	1090-2104		BIOCHEM BIOPH RES CO	Biochem. Biophys. Res. Commun.	JAN 22	2017	482	4					1037	1041		10.1016/j.bbrc.2016.11.154			5	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	EK1XB	WOS:000393720000079	27908725				2022-04-25	
J	Chen, MC; Lin, YC; Liao, YH; Liou, JP; Chen, CH				Chen, Mei-Chuan; Lin, Yu-Chen; Liao, Yu-Hsuan; Liou, Jing-Ping; Chen, Chun-Han			MPT0G612, a Novel HDAC6 Inhibitor, Induces Apoptosis and Suppresses IFN-gamma-Induced Programmed Death-Ligand 1 in Human Colorectal Carcinoma Cells	CANCERS			English	Article						HDAC6; apoptosis; autophagy; PD-L1; colorectal cancer	HISTONE DEACETYLASE INHIBITORS; CANCER; GROWTH; IDENTIFICATION; DEXAMETHASONE; RICOLINOSTAT; ACETYLATION; COMBINATION; EXPRESSION; BORTEZOMIB	Colorectal cancer (CRC) is the third most common cancer and the leading cause of cancer-associated death worldwide. Histone deacetylases (HDACs) have been implicated in regulating complex cellular mechanisms to influence tumor biology and immunogenicity in various types of cancer. The potential of selective inhibition of HDAC6 has been widely discussed for the treatment of hematologic malignancies. We previously identified that MPT0G612 is a novel HDAC6 inhibitor exhibiting a promising antitumor activity against several solid tumors. The purpose of the present study was to evaluate the feasibility and pharmacological mechanisms of MPT0G612 as a potential therapy for CRC patients. Results revealed that MPT0G612 significantly suppresses the proliferation and viability, as well as induces apoptosis in CRC cells. Autophagy activation with LC3B-II formation and p62 degradation was observed, and the inhibition of autophagy by pharmacological inhibitor or Atg5 knockdown enhances MPT0G612-induced cell death. In addition, HDAC6 knockdown reduces MPT0G612-mediated autophagy and further potentiates apoptotic cell death. Furthermore, MPT0G612 downregulates the expression of PD-L1 induced by IFN-gamma in CRC cells. These results suggest that MPT0G612 is a potent cell death inducer through inhibiting HDAC6-associated pathway, and a potential agent for combination strategy with immune checkpoint inhibitors for the treatment of CRC.	[Chen, Mei-Chuan; Liao, Yu-Hsuan] Taipei Med Univ, Coll Pharm, PhD Program Clin Drug Dev Herbal Med, Taipei 110, Taiwan; [Chen, Mei-Chuan] Taipei Med Univ Hosp, Tradit Herbal Med Res Ctr, Taipei 110, Taiwan; [Lin, Yu-Chen; Chen, Chun-Han] Taipei Med Univ, Coll Med, Sch Med, Dept Pharmacol, Taipei 110, Taiwan; [Liou, Jing-Ping] Taipei Med Univ, Coll Pharm, Sch Pharm, Taipei 110, Taiwan; [Chen, Chun-Han] Taipei Med Univ, Wan Fang Hosp, Cell Physiol & Mol Image Res Ctr, Taipei 110, Taiwan		Chen, CH (corresponding author), Taipei Med Univ, Coll Med, Sch Med, Dept Pharmacol, Taipei 110, Taiwan.; Chen, CH (corresponding author), Taipei Med Univ, Wan Fang Hosp, Cell Physiol & Mol Image Res Ctr, Taipei 110, Taiwan.	mcchen1250@tmu.edu.tw; amylin0083@tmu.edu.tw; a0916143813@gmail.com; jpl@tmu.edu.tw; brianchc@tmu.edu.tw			Ministry of Science and Technology of the Republic of ChinaMinistry of Science and Technology, China [MOST 107-2320-B-038-039]; Taipei Medical University [TMU104-AE1-B32]	This research was funded by the Ministry of Science and Technology of the Republic of China, grant number MOST 107-2320-B-038-039, and by Taipei Medical University, grand number TMU104-AE1-B32.	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J	Zhidkov, ME; Smirnova, PA; Tryapkin, OA; Kantemirov, AV; Khudyakova, YV; Malyarenko, OS; Ermakova, SP; Grigorchuk, VP; Kaune, M; von Amsberg, G; Dyshlovoy, SA				Zhidkov, Maxim E.; Smirnova, Polina A.; Tryapkin, Oleg A.; Kantemirov, Alexey V.; Khudyakova, Yuliya V.; Malyarenko, Olesya S.; Ermakova, Svetlana P.; Grigorchuk, Valeria P.; Kaune, Moritz; von Amsberg, Gunhild; Dyshlovoy, Sergey A.			Total Syntheses and Preliminary Biological Evaluation of Brominated Fascaplysin and Reticulatine Alkaloids and Their Analogues	MARINE DRUGS			English	Article						total synthesis; 14-bromoreticulatine; 3; 10-dibromofascaplysin; bioactivity	1ST SYNTHESES; MARINE; PIGMENT; APOPTOSIS; SESTERTERPENE; ANGIOGENESIS; INHIBITION; AUTOPHAGY; CARBOLINE; PRODUCTS	A simple approach toward the synthesis of the marine sponge derived pigment fascaplysin was used to obtain the marine alkaloids 3-bromofascaplysin and 3,10-dibromofascaplysin. These compounds were used for first syntheses of the alkaloids 14-bromoreticulatate and 14-bromoreticulatine. Preliminary bioassays showed that 14-bromoreticulatine has a selective antibiotic (to Pseudomonas aeruginosa) activity and reveals cytotoxicity toward human melanoma, colon, and prostate cancer cells. 3,10-Dibromofascaplysin was able to target metabolic activity of the prostate cancer cells, without disrupting cell membrane's integrity and had a wide therapeutic window amongst the fascaplysin alkaloids.	[Zhidkov, Maxim E.; Smirnova, Polina A.; Tryapkin, Oleg A.; Kantemirov, Alexey V.; Dyshlovoy, Sergey A.] Far Eastern Fed Univ, Sch Nat Sci, Dept Organ Chem, 8 Sukhanov Str, Vladivostok 690950, Russia; [Zhidkov, Maxim E.; Smirnova, Polina A.; Tryapkin, Oleg A.; Kantemirov, Alexey V.; Dyshlovoy, Sergey A.] Far Eastern Fed Univ, Sch Nat Sci, Lab Biol Act Cpds, 8 Sukhanov Str, Vladivostok 690950, Russia; [Khudyakova, Yuliya V.; Malyarenko, Olesya S.; Ermakova, Svetlana P.; Dyshlovoy, Sergey A.] GB Elyakov Pacific Inst Bioorgan Chem, 159 Prospekt 100 Let Vladivostoku, Vladivostok 690022, Russia; [Grigorchuk, Valeria P.] Russian Acad Sci, Inst Biol & Soil Sci, Fed Sci Ctr East Asia Terr Biodivers, Far Eastern Branch, 159 Prospect 100 Let Vladivostoku, Vladivostok 690022, Russia; [Kaune, Moritz; von Amsberg, Gunhild; Dyshlovoy, Sergey A.] Univ Med Ctr Hamburg Eppendorf, Hubertus Wald Tumorzentrum, Dept Oncol Hematol & Bone Marrow Transplantat, Sect Pneumol, D-20246 Hamburg, Germany; [von Amsberg, Gunhild; Dyshlovoy, Sergey A.] Univ Hosp Hamburg Eppendorf, Martini Klin, Prostate Canc Ctr, D-20246 Hamburg, Germany		Zhidkov, ME (corresponding author), Far Eastern Fed Univ, Sch Nat Sci, Dept Organ Chem, 8 Sukhanov Str, Vladivostok 690950, Russia.; Zhidkov, ME (corresponding author), Far Eastern Fed Univ, Sch Nat Sci, Lab Biol Act Cpds, 8 Sukhanov Str, Vladivostok 690950, Russia.	mzhidkov@rambler.ru	Grigorchuk, Valeria/T-3780-2018; Tryapkin, Oleg/AAP-7891-2021; Ermakova, Svetlana P/G-2766-2013; Malyarenko, Olesya/AAQ-6336-2021; Dyshlovoy, Sergey A./B-3586-2013; , Maxim/F-1272-2014	Malyarenko, Olesya/0000-0002-3262-0373; Dyshlovoy, Sergey A./0000-0002-7155-9245; Tryapkin, Oleg/0000-0001-8732-0055; , Maxim/0000-0001-5754-2554	FEFU Endowment Foundation [D-349-17]	This research was funded by the FEFU Endowment Foundation grant number D-349-17. And the APC was funded by grant D-349-17.	Bharate SB, 2012, MINI-REV MED CHEM, V12, P650; Bharate SB, 2012, MEDCHEMCOMM, V3, P1098, DOI 10.1039/c2md20076g; Bilay T. 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Drugs	SEP	2019	17	9							496	10.3390/md17090496			12	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	JA6NS	WOS:000487959700026	31450717	Green Published, gold			2022-04-25	
J	Martinez-Delgado, G; Felix, R				Martinez-Delgado, Gustavo; Felix, Ricardo			Emerging Role of Ca(V)1.2 Channels in Proliferation and Migration in Distinct Cancer Cell Lines	ONCOLOGY			English	Review						Ca2+ channels; Ca(V)1.2 channels; Cancer; Cell proliferation; Autophagy	CALCIUM-CHANNEL; ION CHANNELS; FIBROBLAST CELL; COLON-CANCER; CA2+; GROWTH; PROGRESSION; ANTAGONISTS; EXPRESSION; PROTEIN	Extensive research is currently underway, seeking better diagnostic methods and treatments and a better understanding of the molecular mechanisms involved in cancer, from the role of specific genetic mutations to the intricate biochemical and molecular pathways involved. Because of their role in regulating relevant physiological events such as cell proliferation, migration, and invasion, ion channels have recently been recognized as important elements in cancer initiation and progression. Moreover, it has been reported that pharmacological intervention in ion channel activity might provide protection against diverse types of cancer, and that ion channels could be used as targets to counteract tumor growth, prevent metastasis, and overcome the therapy resistance of tumor cells. In this context, Ca2+ channels have been found to play a role in tumorigenesis and tumor progression. Specifically, L-type Ca2+ channel inhibition may affect cell proliferation, differentiation, and apoptosis. This review aims to provide insights into the potential role of these channels in cancer cell lines, emphasizing their participation in cell proliferation, migration, and autophagy induction, as well as their potential as rational targets for new cancer therapeutics. (C) 2017 S. Karger AG, Basel	[Martinez-Delgado, Gustavo] Inst Nacl Med Genom, Consejo Nacl Ciencia & Tecnol CONACYT, Lab Genom Enfermedades Cardiovasc, Mexico City, DF, Mexico; [Felix, Ricardo] IPN, Ctr Res & Adv Studies, Dept Cell Biol, Natl Polytech Inst Cinvestav, Mexico City, DF, Mexico		Martinez-Delgado, G (corresponding author), INMEGEN, Lab Genom Enfermedades Cardiovasc, Perifer Sur 4809, Mexico City 14610, DF, Mexico.; Felix, R (corresponding author), IPN, CINVESTAV, Dept Cell Biol, Ave IPN 2508, Mexico City 07360, DF, Mexico.	gmartinezd@inmegen.gob.mx; rfelix@cinvestav.mx	Felix, Ricardo/A-6989-2008; Martinez-Delgado, Gustavo/X-7033-2019	Felix, Ricardo/0000-0002-5383-7176; Martinez-Delgado, Gustavo/0000-0003-4655-3770	Conacyt-MexicoConsejo Nacional de Ciencia y Tecnologia (CONACyT) [221660]	The authors appreciate the critical review of Dr. Maria T. Villarreal. Work in the Genomics of Cardiovascular Diseases Laboratory is founded by the National Institute of Genomic Medicine (INMEGEN) and the National Council for Science and Technology (Conacyt-Mexico). Work in the Felix laboratory is partially founded by Conacyt-Mexico (grant 221660). Finally, we also thank the 3 anonymous reviewers commissioned by Oncology for their insightful comments and criticisms.	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J	Zhou, L; Li, S; Sun, J				Zhou, L.; Li, S.; Sun, J.			Ginkgolic acid induces apoptosis and autophagy of endometrial carcinoma cells via inhibiting PI3K/Akt/mTOR pathway in vivo and in vitro	HUMAN & EXPERIMENTAL TOXICOLOGY			English	Article						Ginkgolic acid; PI3K; Akt; MTOR; endometrial cancer; apoptosis; autophagy	BREAST-CANCER; COLON-CANCER; PHOSPHATIDYLINOSITOL; EXPRESSION; GROWTH	Endometrial cancer (EC) is the fourth most common malignancy in women in developed countries. The prognosis of EC is extremely poor, and it is an important factor that contributes to the death of patients. Therefore, studying EC pathogenesis and therapeutic targets, and exploring effective drugs are the primary tasks to improve the prognosis of EC. In the present study, we aimed to explore the function of ginkgolic acid (GA) in EC cell apoptosis and autophagy through PI3K/Akt/mTOR signal pathway in vitro and in vivo. Firstly, MTT assay and clone formation assay were employed to analyze the Ishikawa and HEC-1-B cell viabilities and proliferation after treatment with GA. The results showed that GA inhibited endometrial cancer cell survival. Flow cytometry assay and western blot assay were applied to examine the apoptosis and apoptosis related protein Bcl-2, Bax, Cleaved caspase-3 expression levels of Ishikawa and HEC-1-B cells after treatment with GA. Next, we applied western blot assay to analyze the autophagy associated proteins LC3I, LC3II, p62 and Beclin-1 in GA treated Ishikawa and HEC-1-B cells. We found that GA promoted apoptosis and induced autophagy of endometrial cancer cells. Meanwhile, western blot assay was also used to determine the expression levels of the PI3K/Akt/mTOR signal pathway related protein and the results revealed that GA inhibited the activity of PI3K/Akt/mTOR pathway. Finally, we found that GA inhibited tumor growth in vivo through immunohistochemistry assay. In conclusion, GA induces apoptosis and autophagy of EC cells via inhibiting PI3K/Akt/mTOR pathway in vivo and vitro.	[Zhou, L.; Li, S.] Henan Univ Chinese Med, Dept Obstet & Gynaecol, Affiliated Hosp 1, 19 Renmin Rd, Zhengzhou 450000, Henan, Peoples R China; [Sun, J.] Henan Univ Chinese Med, Dept Obstet & Gynaecol, Zhengzhou, Henan, Peoples R China		Li, S (corresponding author), Henan Univ Chinese Med, Dept Obstet & Gynaecol, Affiliated Hosp 1, 19 Renmin Rd, Zhengzhou 450000, Henan, Peoples R China.	lishurong54321@163.com			Youth fund of National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [82004412]	The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Youth fund of National Natural Science Foundation of China (Grant No. 82004412).	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Exp. Toxicol.	DEC	2021	40	12					2156	2164	09603271211023789	10.1177/09603271211023789		JUN 2021	9	Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Toxicology	XG8WY	WOS:000669076300001	34132136				2022-04-25	
J	Zhang, N; Peng, F; Wang, YJ; Yang, L; Wu, FB; Wang, XY; Ye, C; Han, B; He, G				Zhang, Nan; Peng, Fu; Wang, Yujia; Yang, Li; Wu, Fengbo; Wang, Xiaoyun; Ye, Cui; Han, Bo; He, Gu			Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis	INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES			English	Article						Shikonin; Colorectal carcinoma; Galectin-1; apoptosis; autophagy	CANCER-CELLS; ACTIVATION; JNK; DERIVATIVES; INHIBITOR; DEATH; IDENTIFICATION; GLYCOSYLATION; INFLAMMATION; MODULATION	Colorectal carcinoma (CRC) is the third most common malignant tumor pathology worldwide. Despite progress in surgical procedures and therapy options, CRC is still a considerable cause of cancer-related mortality. In this study, we tested the antitumor effects of shikonin in CRC and tried to identify its potential mechanism. The potential target, molecular mechanism as well as in vitro and in vivo antitumor effects of shikonin in CRC cells were determined by an integrative protocol including quantitative proteomics, RT-PCR, western blotting, RNA interference and overexpression, apoptosis and autophagy assays, etc. Galectin-1 was a potential target of shikonin from the iTRAQ-based proteomic analysis in shikonin-treated SW620 cell. The overexpression and RNA silencing of galectin-1 in two CRC cells suggested that the shikonin sensitivity was correlation to galectin-1 levels. The ROS accumulation induced by shikonin was important to the formation of galectin-1 dimers. Dimer galectin-1 was found to be associated with the activation of JNK and downstream apoptosis or autophagy. Moreover, through functional in vitro studies, we showed that differences in galectin-1 level affected tumor cell proliferation, migration, and invasion. In summary, shikonin induced CRC cells apoptosis and autophagy by targeting galectin-1 and JNK signaling pathway both in vitro and in vivo, which suggested a potential novel therapy target for CRC.	[Zhang, Nan; Ye, Cui; Han, Bo] Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Sichuan, Peoples R China; [Peng, Fu; Wang, Yujia; Yang, Li; Wu, Fengbo; Wang, Xiaoyun; He, Gu] Sichuan Univ, State Key Lab Biotherapy, West China Hosp, Chengdu 610041, Sichuan, Peoples R China; [Peng, Fu; Wang, Yujia; Yang, Li; Wu, Fengbo; Wang, Xiaoyun; He, Gu] Sichuan Univ, Ctr Canc, West China Hosp, Chengdu 610041, Sichuan, Peoples R China; [Peng, Fu; Wang, Yujia; Yang, Li; Wu, Fengbo; Wang, Xiaoyun; He, Gu] Sichuan Univ, West China Sch Pharm, Chengdu 610041, Sichuan, Peoples R China		Han, B (corresponding author), Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Sichuan, Peoples R China.; He, G (corresponding author), Sichuan Univ, State Key Lab Biotherapy, West China Hosp, Chengdu 610041, Sichuan, Peoples R China.; He, G (corresponding author), Sichuan Univ, Ctr Canc, West China Hosp, Chengdu 610041, Sichuan, Peoples R China.; He, G (corresponding author), Sichuan Univ, West China Sch Pharm, Chengdu 610041, Sichuan, Peoples R China.	hanbo@cdutcm.edu.cn; hegu@scu.edu.cn	He, Gu/G-5446-2015	He, Gu/0000-0002-1536-8882	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21772131, 81630101, 81891012, 81573588, 81773889]; Science & Technology Department of Sichuan Province [2017JZYD0001, 2017JY0323, 2019YFSY0004]	We are grateful for financial support from the National Natural Science Foundation of China (21772131, 81630101, 81891012, 81573588 and 81773889), the Science & Technology Department of Sichuan Province (2017JZYD0001, 2017JY0323 and 2019YFSY0004).	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J. Biol. Sci.		2020	16	1					147	161		10.7150/ijbs.36955			15	Biochemistry & Molecular Biology; Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics	JR4VF	WOS:000499624000012	31892852	Green Published, gold			2022-04-25	
J	Xing, Y; Wang, ZH; Ma, DH; Han, Y				Xing, Ying; Wang, Zhi Hong; Ma, Dong Hong; Han, Ying			FTY720 enhances chemosensitivity of colon cancer cells to doxorubicin and etoposide via the modulation of P-glycoprotein and multidrug resistance protein 1	JOURNAL OF DIGESTIVE DISEASES			English	Article						apoptosis; multidrug resistance protein 1; P-glycoprotein; chemotherapy; multidrug resistance; FTY720	HEPATOCELLULAR-CARCINOMA CELLS; GASTRIC-CANCER; TUMOR-GROWTH; IN-VITRO; FINGOLIMOD FTY720; ABC TRANSPORTERS; DRUG-RESISTANCE; APOPTOSIS; EXPRESSION; AUTOPHAGY	Objective This study aimed to investigate the effects of FTY720 on inducing cell growth inhibition and enhancing the cytotoxicity of anti-cancer drugs in the human colon cancer cell line HCT-8 and its multidrug-resistant cell line HCT-8/5-fluorouracil (HCT-8/5-Fu). Methods Cell viability and apoptosis after being treated with FTY720 alone or in combination with doxorubicin (DOX) and etoposide (VP16) were tested in HCT-8 and HCT-8/5-Fu cells. The changes in P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) were determined at the mRNA and functional levels. Results FTY720 showed anti-proliferative activity against cancer cells in a dose-dependent and time-dependent manner and could enhance the cytotoxicity of DOX and VP16 in both HCT-8 and HCT-8/5-Fu cell lines. In addition, treatment with FTY720 resulted in the promotion of VP16-induced cell apoptosis and an increased accumulation of intracellular DOX and two specific fluorescent substrates of P-gp and MRP1 through the inhibition of efflux and the suppression of gene expression. Conclusion FTY720 exerts its chemosensitization effect in HCT-8 and HCT-8/5-Fu cell lines by promoting cell apoptosis and inhibiting P-gp and MRP1, which could be applied as a potential co-adjuvant therapeutic modality.	[Xing, Ying] Gen Hosp Beijing Mil Command, Med Sch Chinese PLA, Beijing 100700, Peoples R China; [Wang, Zhi Hong; Ma, Dong Hong; Han, Ying] Gen Hosp Beijing Mil Command, Dept Gastroenterol, Beijing 100700, Peoples R China		Han, Y (corresponding author), Gen Hosp Beijing Mil Command, Dept Gastroenterol, 5 Nanmencang, Beijing 100700, Peoples R China.	yh721303@sina.com					Alinari L, 2011, BLOOD, V118, P6893, DOI 10.1182/blood-2011-06-363879; Azuma H, 2002, CANCER RES, V62, P1410; Azuma H, 2003, J UROLOGY, V169, P2372, DOI 10.1097/01.ju.0000064938.32318.91; Berdyshev EV, 2009, J BIOL CHEM, V284, P5467, DOI 10.1074/jbc.M805186200; Cannon RE, 2012, P NATL ACAD SCI USA, V109, P15930, DOI 10.1073/pnas.1203534109; [陈洁 Chen Jie], 2013, [电力系统保护与控制, Power System Protection and Control], V41, P7; Chen ZS, 2011, FEBS J, V278, P3226, DOI 10.1111/j.1742-4658.2011.08235.x; Choi YH, 2014, CURR PHARM DESIGN, V20, P793, DOI 10.2174/138161282005140214165212; Du JP, 2005, INT J CANCER, V113, P213, DOI 10.1002/ijc.20570; Estrada-Bernal A, 2012, NEURO-ONCOLOGY, V14, P405, DOI 10.1093/neuonc/nos005; Gottesman MM, 2002, NAT REV CANCER, V2, P48, DOI 10.1038/nrc706; Gouaze-Andersson V, 2007, BBA-MOL CELL BIOL L, V1771, P1407, DOI 10.1016/j.bbalip.2007.09.005; Han Z, 2007, J EXP CLIN CANC RES, V26, P261; Hao ZM, 2006, CANCER BIOL THER, V5, P261, DOI 10.4161/cbt.5.3.2381; HIDALGO IJ, 1989, GASTROENTEROLOGY, V96, P736; Honig SM, 2003, J CLIN INVEST, V111, P627, DOI 10.1172/JCI200316200; Hung JH, 2008, CANCER RES, V68, P1204, DOI 10.1158/0008-5472.CAN-07-2621; Ingwersen J, 2012, CLIN IMMUNOL, V142, P15, DOI [10.1016/j.clim.2011.05.005, 10.1016/j.clim.2011.10.008]; Kappos L, 2006, NEW ENGL J MED, V355, P1124, DOI 10.1056/NEJMoa052643; Lahiri S, 2009, J BIOL CHEM, V284, P16090, DOI 10.1074/jbc.M807438200; Lainey E, 2012, CELL CYCLE, V11, P4079, DOI 10.4161/cc.22382; Lebedeva IV, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0022429; Li MH, 2013, PEDIATR BLOOD CANCER, V60, P1418, DOI 10.1002/pbc.24564; Liao AJ, 2012, EUR J PHARM SCI, V45, P600, DOI 10.1016/j.ejps.2011.12.014; Limtrakul P, 2007, MOL CELL BIOCHEM, V296, P85, DOI 10.1007/s11010-006-9302-8; Liscovitch M, 2000, TRENDS BIOCHEM SCI, V25, P530, DOI 10.1016/S0968-0004(00)01668-6; Lohoff M, 1998, J CLIN INVEST, V101, P703, DOI 10.1172/JCI824; Matloubian M, 2004, NATURE, V427, P355, DOI 10.1038/nature02284; MOSMANN T, 1983, J IMMUNOL METHODS, V65, P55, DOI 10.1016/0022-1759(83)90303-4; Neviani P, 2007, J CLIN INVEST, V117, P2408, DOI 10.1172/JCI31095; Patel A, 2013, CANCER CHEMOTH PHARM, V72, P189, DOI 10.1007/s00280-013-2184-z; Pchejetski D, 2010, CANCER RES, V70, P8651, DOI 10.1158/0008-5472.CAN-10-1388; Pyne NJ, 2010, NAT REV CANCER, V10, P489, DOI 10.1038/nrc2875; Rocha GD, 2012, INT J MOL SCI, V13, P6757, DOI 10.3390/ijms13066757; ROSS DD, 1993, BLOOD, V82, P1288; Saida T, 2012, MULT SCLER J, V18, P1269, DOI 10.1177/1352458511435984; Schnab KL, 2009, BRIT J NUTR, V101, P694, DOI 10.1017/S0007114508048289; Sui H, 2012, J INT MED RES, V40, P426, DOI 10.1177/147323001204000204; Szakacs G, 2006, NAT REV DRUG DISCOV, V5, P219, DOI 10.1038/nrd1984; Tang JL, 2013, CANCER LETT, V336, P149, DOI 10.1016/j.canlet.2013.04.020; Ubai T, 2007, ANTICANCER RES, V27, P75; Wang HL, 2013, ONCOL REP, V29, P676, DOI 10.3892/or.2012.2156; Wang J, 2012, AAPS ANN M EXP; Yang L, 2011, PHYTOMEDICINE, V18, P710, DOI 10.1016/j.phymed.2010.11.017; Yasui H, 2005, CANCER RES, V65, P7478, DOI 10.1158/0008-5472.CAN-05-0850; Ye CG, 2011, CANCER LETT, V304, P90, DOI 10.1016/j.canlet.2011.01.025; Yin X, 2013, INT J GYNECOL CANCER, V23, P630, DOI 10.1097/IGC.0b013e3182892cee; Zhang N, 2010, AUTOPHAGY, V6, P1157, DOI 10.4161/auto.6.8.13614; Zheng TS, 2010, J CELL BIOCHEM, V111, P218, DOI 10.1002/jcb.22691	49	20	22	0	12	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1751-2972	1751-2980		J DIGEST DIS	J. Dig. Dis.	MAY	2014	15	5					246	259		10.1111/1751-2980.12131			14	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	AF4LT	WOS:000334684800005	24868599				2022-04-25	
J	Gao, L; Sun, X; Zhang, Q; Chen, XC; Zhao, TW; Lu, LQ; Zhang, JB; Hong, YP				Gao, Liang; Sun, Xin; Zhang, Qi; Chen, Xiaochen; Zhao, Tongwei; Lu, Liqing; Zhang, Jianbin; Hong, Yupeng			Histone deacetylase inhibitor trichostatin A and autophagy inhibitor chloroquine synergistically exert anti-tumor activity in H-ras transformed breast epithelial cells	MOLECULAR MEDICINE REPORTS			English	Article						trichostatin A; histone deacetylase inhibitor; apoptosis; autophagy; MCF10A-ras cells; chloroquine	APOPTOSIS; CANCER; DEATH; MECHANISMS; EXPRESSION; CARCINOMA; SURVIVAL; THERAPY	Histone deacetylase inhibitors (HDACIs) cause oncogene-transformed mammalian cell death. Our previous study indicated that HDACIs activate forkhead box O1 (FOXO1) and induce autophagy in liver and colon cancer cells. However, whether FOXO1 is involved in HDACI-mediated oncogene-transformed mammalian cell death remains unclear. In the present study, H-ras transformed MCF10A cells were used to investigate the role of FOXO1 in this pathway. Results showed that trichostatin A (TSA), a HDACI, activated apoptosis in MCF10A-ras cells, but not in MCF10A cells. Furthermore, TSA activated FOXO1 via P21 upregulation, whereas the knockdown of FOXO1 reduced TSA-induced cell death. In addition, TSA induced autophagy in MCF10A and MCF10A-ras cells by blocking the mammailian target of rapamycin signaling pathway. Furthermore, autophagy inhibition lead to higher MCF10A-ras cell death by TSA, thus indicating that autophagy is essential in cell survival. Taken together, the present study demonstrated that TSA causes oncogene-transformed cell apoptosis via activation of FOXO1 and HDACI-mediated autophagy induction, which served as important cell survival mechanisms. Notably, the present findings imply that a combination of HDACIs and autophagy inhibitors produce a synergistic anticancer effect.	[Gao, Liang; Sun, Xin; Chen, Xiaochen; Zhao, Tongwei; Lu, Liqing; Zhang, Jianbin; Hong, Yupeng] Hangzhou Med Coll, Peoples Hosp, Zhejiang Prov Peoples Hosp, Dept Oncol, 158 Shangtang Rd, Hangzhou 310014, Zhejiang, Peoples R China; [Zhang, Qi] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Hepatobiliary & Pancreat Surg, Hangzhou 310002, Zhejiang, Peoples R China		Zhang, JB; Hong, YP (corresponding author), Hangzhou Med Coll, Peoples Hosp, Zhejiang Prov Peoples Hosp, Dept Oncol, 158 Shangtang Rd, Hangzhou 310014, Zhejiang, Peoples R China.	zhangjianbin@hmc.edu.cn; hypbdn@zju.edu.cn			Science Technology Department of Zhejiang Province, China [2015C33173]; Traditional Chinese Medicine Fund of Zhejiang Province, China [2011ZA010]; Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [LQ18H280006]	This study was financially supported by the Science Technology Department of Zhejiang Province, China (grant no. 2015C33173), the Traditional Chinese Medicine Fund of Zhejiang Province, China (grant no. 2011ZA010) and the Zhejiang Provincial Natural Science Foundation of China (grant no. LQ18H280006).	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Med. Rep.	MAR	2018	17	3					4345	4350		10.3892/mmr.2018.8446			6	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	FV2MB	WOS:000424400000116	29344672	hybrid, Green Submitted, Green Published			2022-04-25	
J	Zhuang, PW; Zhang, JB; Wang, Y; Zhang, MX; Song, LL; Lu, ZQ; Zhang, L; Zhang, FQ; Wang, J; Zhang, YJ; Wei, HJ; Li, HY				Zhuang, Pengwei; Zhang, Jinbao; Wang, Yan; Zhang, Mixia; Song, Lili; Lu, Zhiqiang; Zhang, Lu; Zhang, Fengqi; Wang, Jing; Zhang, Yanjun; Wei, Hongjun; Li, Hongyan			Reversal of muscle atrophy by Zhimu and Huangbai herb pair via activation of IGF-1/Akt and autophagy signal in cancer cachexia	SUPPORTIVE CARE IN CANCER			English	Article						Cancer cachexia; Skeletal muscle atrophy; Zhimu and Huangbai herb pair; Autophagy; IGF-1/Akt	GROWTH-FACTOR-I; SKELETAL-MUSCLE; MICE; MASS; ADENOCARCINOMA; IDENTIFICATION; INTERLEUKIN-6; DOWNSTREAM; EXPRESSION; BERBERINE	Muscle atrophy is the prominent clinical feature of cancer-induced cachexia. Zhimu and Huangbai herb pair (ZBHP) has been used since ancient China times and have been phytochemically investigated for constituents that might cause anti-cancer, diabetes, and their complication. In this study, the effects and mechanisms of ZBHP on reversal of muscle atrophy were explored. C57BL/6 mice implanted with colon-26 adenocarcinoma were chosen to develop cancer cachexia for evaluating the effects of ZBHP on reversal of muscle atrophy. The body weight, survival time, inflammatory cytokines, and pathological changes of muscle were monitored. In addition, IGF-1/Akt and autophagy pathway members were analyzed to interpret the mechanism of drug response. The function and morphology of skeletal muscle in cachexia model were significantly disturbed, and the survival time was shortened. Consistently, inflammatory cytokines and muscle atrophy-related atrogin-1, MuRF1, and FOXO3 were significantly increased, and IGF-1/Akt and autophagy signal pathways were depressed. Treatment with ZBHP significantly alleviated tumor-free body weight reduction and cachexia-induced changes in cytokines and prolonged survival. ZBHP treatment not only inhibited the muscle atrophy-related genes but also activated the IGF-1/Akt and autophagy signal pathways to facilitate the protein synthesis. The results revealed that ZBHP treatment could inhibit the muscle atrophy induced by cancer cachexia and prolong the survival time, and ZBHP may be of value as a pharmacological alternative in treatment of cancer cachexia.	[Zhuang, Pengwei; Zhang, Jinbao; Wang, Yan; Zhang, Mixia; Song, Lili; Lu, Zhiqiang; Zhang, Lu; Zhang, Fengqi; Wang, Jing; Zhang, Yanjun] Tianjin Univ Tradit Chinese Med, Chinese Mat Med Coll, 312 Anshanxi Rd, Tianjin 300193, Peoples R China; [Zhuang, Pengwei; Wang, Yan; Zhang, Mixia; Song, Lili; Zhang, Yanjun] Tianjin Univ Tradit Chinese Med, Tianjin State Key Lab Modern Chinese Med, 312 Anshanxi Rd, Tianjin 300193, Peoples R China; [Zhuang, Pengwei; Wei, Hongjun; Li, Hongyan] Tianjin JF Pharmaland Technol Dev Co Ltd, Tianjin, Peoples R China; [Zhang, Jinbao] Gansu Univ Chinese Med, Lanzhou, Gansu, Peoples R China		Zhang, YJ (corresponding author), Tianjin Univ Tradit Chinese Med, Chinese Mat Med Coll, 312 Anshanxi Rd, Tianjin 300193, Peoples R China.; Zhang, YJ (corresponding author), Tianjin Univ Tradit Chinese Med, Tianjin State Key Lab Modern Chinese Med, 312 Anshanxi Rd, Tianjin 300193, Peoples R China.	zyjsunye@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81403213]; Program for Changjiang Scholars and Innovative Research Team in University ("PCSIRT")Program for Changjiang Scholars & Innovative Research Team in University (PCSIRT) [IRT 14R41]	This work was supported by the National Natural Science Foundation of China (no. 81403213) and Program for Changjiang Scholars and Innovative Research Team in University ("PCSIRT", IRT 14R41).	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Care Cancer	MAR	2016	24	3					1189	1198		10.1007/s00520-015-2892-5			10	Oncology; Health Care Sciences & Services; Rehabilitation	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Health Care Sciences & Services; Rehabilitation	DC1WY	WOS:000369010000021	26280404				2022-04-25	
J	Yang, L; Cai, YS; Xu, K; Zhu, JL; Li, YB; Wu, XQ; Sun, J; Lu, SM; Xu, P				Yang, Le; Cai, Yong-Song; Xu, Ke; Zhu, Jia-Lin; Li, Yuan-Bo; Wu, Xiao-Qing; Sun, Jian; Lu, She-Min; Xu, Peng			Sodium selenite induces apoptosis and inhibits autophagy in human synovial sarcoma cell line SW982 in vitro	MOLECULAR MEDICINE REPORTS			English	Article						synovial sarcoma; SW982 cell line; sodium selenite; apoptosis; autophagy	COLON-CANCER CELLS; MITOCHONDRIAL PATHWAY; CARCINOMA-CELLS; DOWN-REGULATION; NB4 CELLS; CHEMOTHERAPY; SUPPRESSION; ACTIVATION; RAPAMYCIN; TOXICITY	The present study aimed to examine the effects of sodium selenite on the SW982 human synovial sarcoma cell line in relation to cell viability, apoptosis and autophagy. The results indicated that sodium selenite reduced cell viability and induced apoptosis by activating caspase-3 and members of the poly (ADP-ribose) polymerase and Bcl-2 protein families in SW982 cells. Furthermore, autophagy was also suppressed by sodium selenite treatment in SW982 cells, and apoptosis was upregulated in cells co-treated with sodium selenite and the autophagy inhibitor 3-methyladenine. By contrast, apoptosis was downregulated when sodium selenite was combined with rapamycin, an inducer of autophagy. The results indicated that autophagy may protect cells from the cytotoxicity of sodium selenite. The present study results demonstrated that sodium selenite induced apoptosis and inhibited autophagy and autophagy-protected cells from death by antagonizing sodium selenite-induced apoptosis in SW982 cells in vitro.	[Yang, Le; Cai, Yong-Song; Xu, Ke; Zhu, Jia-Lin; Li, Yuan-Bo; Wu, Xiao-Qing; Xu, Peng] Xi An Jiao Tong Univ, Hlth Sci Ctr, Xian Hong Hui Hosp, Dept Joint Surg, 76 Nanguo Rd, Xian 710054, Shaanxi, Peoples R China; [Sun, Jian; Lu, She-Min] Xi An Jiao Tong Univ, Hlth Sci Ctr, Dept Genet & Mol Biol, Xian 710061, Shaanxi, Peoples R China		Xu, P (corresponding author), Xi An Jiao Tong Univ, Hlth Sci Ctr, Xian Hong Hui Hosp, Dept Joint Surg, 76 Nanguo Rd, Xian 710054, Shaanxi, Peoples R China.	sousou369@163.com	Lu, Shemin/M-3350-2018; Lu, Shemin/AAI-6479-2021	Lu, Shemin/0000-0001-8250-850X; Lu, Shemin/0000-0002-5535-8320	National Natural Science Foundations of ChinaNational Natural Science Foundation of China (NSFC) [81271948, 81601877]	This study was supported by The National Natural Science Foundations of China (grant nos. 81271948 and 81601877).	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Med. Rep.	MAY	2018	17	5					6560	6568		10.3892/mmr.2018.8679			9	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	GD5OR	WOS:000430556800041	29512717	hybrid, Green Published, Green Submitted			2022-04-25	
J	Ballaro, R; Penna, F; Pin, F; Gomez-Cabrera, MC; Vina, J; Costelli, P				Ballaro, Riccardo; Penna, Fabio; Pin, Fabrizio; Carmen Gomez-Cabrera, Mari; Vina, Jose; Costelli, Paola			Moderate Exercise Improves Experimental Cancer Cachexia by Modulating the Redox Homeostasis	CANCERS			English	Article						muscle wasting; oxidative stress; autophagy; chemotherapy; mitochondria	SKELETAL-MUSCLE; OXIDATIVE STRESS; ANIMAL-MODEL; CHEMOTHERAPY; ANTIOXIDANT; AUTOPHAGY; EXPRESSION; PREVENTION; PLASTICITY; INDUCTION	Cachexia is a debilitating syndrome that complicates the management of cancer patients. Muscle wasting, one of the main features of cachexia, is associated with hyper-activation of protein degradative pathways and altered mitochondrial function that could both result from impaired redox homeostasis. This study aimed to investigate the contribution of oxidative stress to cancer-induced cachexia in the presence or in the absence of moderate exercise training. Mice bearing the colon C26 carcinoma, either sedentary or exercised, were used. The former showed muscle wasting and redox imbalance, with the activation of an antioxidant response and with upregulation of markers of proteasome-dependent protein degradation and autophagy. Moderate exercise was able to relieve muscle wasting and prevented the loss of muscle strength; such a pattern was associated with reduced levels of Reactive Oxygen Species (ROS), carbonylated proteins and markers of autophagy and with improved antioxidant capacity. The muscle of sedentary tumor hosts also showed increased levels of molecular markers of mitophagy and reduced mitochondrial mass. Conversely, exercise in the C26 hosts led to increased mitochondrial mass. In conclusion, moderate exercise could be an effective non-pharmacological approach to prevent muscle wasting in cancer patients, decreasing muscle protein catabolism and oxidative stress and preserving mitochondria.	[Ballaro, Riccardo; Penna, Fabio; Pin, Fabrizio; Costelli, Paola] Univ Torino, Expt Med & Clin Pathol Unit, Dept Clin & Biol Sci, I-10125 Turin, Italy; [Ballaro, Riccardo; Penna, Fabio; Pin, Fabrizio; Costelli, Paola] Interuniv Inst Myol, I-61029 Urbino, Italy; [Pin, Fabrizio] Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA; [Carmen Gomez-Cabrera, Mari; Vina, Jose] Univ Valencia, Dept Physiol, Freshage Res Grp, CIBERFES,INCLIVA, Valencia, Spain		Costelli, P (corresponding author), Univ Torino, Expt Med & Clin Pathol Unit, Dept Clin & Biol Sci, I-10125 Turin, Italy.; Costelli, P (corresponding author), Interuniv Inst Myol, I-61029 Urbino, Italy.	riccardo.ballaro@unito.it; fabio.penna@unito.it; fpin@iu.edu; gomez@uv.es; jose.vina@uv.es; Carmen.Gomez@uv.es	Vina, Jose/AAB-3069-2021; Gomez-Cabrera, Maria Carmen/H-6911-2018; Ballarò, Riccardo/ABC-1988-2020; Penna, Fabio/K-5090-2016	Vina, Jose/0000-0001-9709-0089; Gomez-Cabrera, Maria Carmen/0000-0003-4000-1684; Ballarò, Riccardo/0000-0001-5505-9024; Penna, Fabio/0000-0002-2774-6027	Associazione Italiana per la Ricerca sul Cancro [AIRC]Fondazione AIRC per la ricerca sul cancro [IG9153]; University of Torino	Work supported by Associazione Italiana per la Ricerca sul Cancro [AIRC; grant IG9153 (PC)] Milano and University of Torino (ex-60% funds), Italy.	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J	Fu, C; Yu, ZJ; He, Y; Ding, J; Wei, MJ				Fu, Chen; Yu, Zhaojin; He, Ying; Ding, Jian; Wei, Minjie			Down-Regulation of an Autophagy-Related Gene SERPINA1 as a Superior Prognosis Biomarker Associates with Relapse and Distant Metastasis in Colon Adenocarcinoma	ONCOTARGETS AND THERAPY			English	Article						SERPINA1; autophagy; COAD; prognostic; relapse; distant metastasis	CANCER STATISTICS; R PACKAGE; CELLS; EXPRESSION; APOPTOSIS; PROTEINS	Background: The relapse and distant metastasis in colon adenocarcinoma (COAD) patients with a poor prognosis. Autophagy has gained increasing attention recently. Methods: This study utilized univariate Cox analysis from the TCGA database to obtain 10 prognostic autophagy-related genes (ARGs). GO and KEGG functional annotation analysis suggested that the ARGs were significantly enriched in tumor metabolic processes. We verified the autophagy-related genes screened by TCGA clinical data. Then, we compared the expression of SERPINA1 in primary and metastatic tumor cells in the GEO database, and finally verified the relationship between SERPINA1 protein expression and prognosis with the CPTAC database. Results: The ROC curves showed SERPINA1 had robust prediction capability in judging the prognosis and disease process compared with the other 4 ARGs and risk score in COAD. Clinical relationship analysis further indicated SERPINA1 was related to TMN stage, clinical-stage, OS, RFS, and DMFS in COAD. Besides, survival analysis presented that higher expression of SERPINA1 was significantly associated with the longer OS, RFS, or DMFS. Moreover, SERPINA1 protein was validated to be associated with OS, RFS, and DMFS through our own IHC and CPTAC database. Finally, we exploratoryly combined the SERPINA1 mRNA and SERPINA1 protein as a new index for prognostics. Conclusion: This new combined index showed the highest prognostic value for OS, RFS, and DMFS, and had the potential to become a practical biomarker for prognosis.	[Fu, Chen; Yu, Zhaojin; He, Ying; Ding, Jian; Wei, Minjie] China Med Univ, Sch Pharm, Dept Pharmacol, Shenyang 110122, Peoples R China; [Fu, Chen; Yu, Zhaojin; Wei, Minjie] China Med Univ, Dept Pharmacol, Liaoning Key Lab Mol Targeted Antitumor Drug Dev, Shenyang 110122, Peoples R China; [He, Ying] China Med Univ, Affiliated Hosp 4, Dept Oncol, Shenyang 110000, Peoples R China; [Ding, Jian] Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; [Wei, Minjie] Liaoning Med Diag & Treatment Ctr, Shenyang 110000, Peoples R China		Wei, MJ (corresponding author), China Med Univ, Sch Pharm, Dept Pharmacol, Shenyang 110122, Peoples R China.; Ding, J (corresponding author), Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China.	carl.2000@163.com; weiminjiecmu@163.com			National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [82073884]; NSFC-Liaoning joint fund key program [U20A20413]; Major Special S&T Projects in Liaoning Province [2019JH1/10300005]	National Natural Science Foundation of China (NSFC, No. 82073884), NSFC-Liaoning joint fund key program (No. U20A20413), Major Special S&T Projects in Liaoning Province (2019JH1/10300005).	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J	Zhang, ZW; Liu, Z; Chen, J; Yi, J; Cheng, J; Dun, WQ; Wei, HL				Zhang, Zhewen; Liu, Zhuan; Chen, Jing; Yi, Juan; Cheng, Juan; Dun, Wangqing; Wei, Hulai			Resveratrol induces autophagic apoptosis via the lysosomal cathepsin D pathway in human drug-resistant K562/ADM leukemia cells	EXPERIMENTAL AND THERAPEUTIC MEDICINE			English	Article						resveratrol; apoptosis; autophagy; drug resistance; cathepsin D; K562/ADM cells	MULTIDRUG-RESISTANCE; COLORECTAL-CANCER; ARSENIC TRIOXIDE; DOWN-REGULATION; IN-VITRO; DEATH; PROLIFERATION; VIVO	The aim of the present study was to investigate the crosstalk between resveratrol (Res)-induced autophagy and apoptosis, and the molecular pathway by which autophagy leads to apoptotic death in drug-resistant K562/ADM leukemia cells. The viability of K562/ADM cells was determined using the MTT assay. The formation of autophagic vacuoles was detected using transmission electron microscopy and monodansylcadaverine (MDC) staining. Cell apoptosis was evaluated using flow cytometry. The expression of apoptosis-or autophagy-associated proteins was measured using western blotting. The results indicated that treatment with Res inhibited cell viability in a concentration-dependent manner. Furthermore, the numbers of MDC-positive fluorescent points, autophagic vacuoles and autolysosome-engulfed cytoplasmic materials were markedly increased in Res-treated K562/ADM cells compared with untreated cells, as determined using fluorescence microscopy and transmission electron microscopy. Res-induced apoptosis was associated with increased cleaved caspase-3 and B-cell lymphoma 2 associated X protein, and decreased B-cell lymphoma 2 (Bcl-2) protein expression levels when compared with the control (P<0.05). However, the proportion of apoptotic cells decreased from 69.6 to 41.0% (40 mu mol/l Res) and from 77.3 to 58.8% (80 mu mol/l Res) following pre-treatment with the autophagy inhibitor 3-methyladenine (P<0.01). The protein expression levels of microtubule-associated protein 1A/1B-light chain 3 and beclin 1, two markers of autophagy, were upregulated in Res-treated cells compared with the control (P<0.05). In addition, lysosomal cathepsin D (Cath D) release increased during Res-induced autophagy and apoptosis (P<0.05). The present results demonstrated that Res-induced apoptosis of K562/ADM cells was autophagy-dependent and the released Cath D may trigger caspase-dependent cell death through the Bcl-2 family of proteins. Furthermore, the present data indicate that to enhancement of the autophagy-cathepsin-apoptosis pathway may be an effective approach for overcoming anticancer drug resistance.	[Zhang, Zhewen; Liu, Zhuan; Chen, Jing; Yi, Juan; Dun, Wangqing; Wei, Hulai] Lanzhou Univ, Sch Basic Med Sci, Inst Biochem & Mol Biol, Lanzhou 730000, Gansu, Peoples R China; [Cheng, Juan] Lanzhou Univ, Affiliated Hosp 1, Dept Hematol, Lanzhou 730000, Gansu, Peoples R China; [Wei, Hulai] Lanzhou Univ, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, 199 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China		Wei, HL (corresponding author), Lanzhou Univ, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, 199 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China.	weihulai@lzu.edu.cn			Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [lzujbky-2014-143]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81541025]	The present study was supported by the Fundamental Research Funds for the Central Universities (grant no. lzujbky-2014-143) and National Natural Science Foundation of China (grant no. 81541025).	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Ther. Med.	MAR	2018	15	3					3012	3019		10.3892/etm.2018.5742			8	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	FZ6XI	WOS:000427743500119	29456707	gold, Green Published			2022-04-25	
J	Chen, ZH; Li, YC; Zhang, C; Yi, HM; Wu, C; Wang, JP; Liu, YW; Tan, JQ; Wen, JF				Chen, Zhihong; Li, Yanchun; Zhang, Chi; Yi, Hongmei; Wu, Chang; Wang, Junpu; Liu, Yuwu; Tan, Jieqiong; Wen, Jifang			Downregulation of Beclin1 and Impairment of Autophagy in a Small Population of Colorectal Cancer	DIGESTIVE DISEASES AND SCIENCES			English	Article						Colorectal cancer; Beclin 1; Autophagy; Rapamycin	TUMOR-SUPPRESSOR; P53 MUTATIONS; CELL-LINES; EXPRESSION; GENE; TUMORIGENESIS; INHIBITION; APOPTOSIS; PROTEIN; PROGNOSIS	Background Autophagy is a highly conserved mechanism for degradation and recycling of long-lived proteins and damaged organelle to maintain cell homeostasis. Deregulation of autophagy has been associated with tumorigenesis. Beclin 1 is an essential autophagy protein and its upregulation has been observed in most colorectal cancer tissues. However, there is a small population of colorectal cancers with downregulation of Beclin 1. Aim The purpose of this study was to investigate the role autophagy plays in colorectal cancers with downregulaion of Beclin 1. Methods LC3 protein, an autophagosome marker, was assessed by ICH and WB in colorectal cancers tissues. An anti-tumor effect of Beclin 1 was examined by introducing exogenous Beclin 1 in vitro. Colony formation assay, growth curves and mouse xenograft were analysed. Results Our results showed that LC3 was suppressed in the colorectal cancers (9.86 %) with downregulation of Beclin 1. Moreover, overexpression of Beclin 1 inhibited colorectal cancer cell growth and enhanced the rapamycin-induced antitumor effect in vitro. Conclusion Downregulation of Beclin 1 and autophagy inhibition play an important role in a part of colorectal cancers. Activating autophagy or overexperssion of Beclin 1 may be an effective treatment for some colorectal cancers. Detection of expression profile of Beclin 1 in colorectal cancers could be a strategy for new diagnostic and therapeutic methods.	[Chen, Zhihong; Wu, Chang; Wang, Junpu; Liu, Yuwu; Wen, Jifang] Cent S Univ, Sch Basic Med, Dept Pathol, Changsha 410013, Hunan, Peoples R China; [Chen, Zhihong; Li, Yanchun; Yi, Hongmei] Hunan Prov Peoples Hosp, Dept Pathol, Changsha 410005, Hunan, Peoples R China; [Zhang, Chi] Univ South China, Funct Lab Ctr, Hengyang 421001, Peoples R China; [Tan, Jieqiong] Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China		Wen, JF (corresponding author), Cent S Univ, Sch Basic Med, Dept Pathol, 172 Tong Zi Po Rd, Changsha 410013, Hunan, Peoples R China.	zhihong6662002@yahoo.com.cn; liyanchun99@yahoo.cn; zhangchi9966@163.com; yihongmei2012@yahoo.cn; wuchang_scs@163.com; junpuwang1212@yahoo.cn; liuyuwu_8923@yahoo.cn; tanjieqiong@sklmg.edu.cn; jifang.wen@yahoo.com.cn					Ahn CH, 2007, APMIS, V115, P1344, DOI 10.1111/j.1600-0463.2007.00858.x; Aita VM, 1999, GENOMICS, V59, P59, DOI 10.1006/geno.1999.5851; Chen N, 2009, BBA-MOL CELL RES, V1793, P1516, DOI 10.1016/j.bbamcr.2008.12.013; Cho DH, 2012, ANTICANCER RES, V32, P4091; ECCLES DM, 1990, ONCOGENE, V5, P1599; Fu LL, 2013, INT J BIOCHEM CELL B, V45, P921, DOI 10.1016/j.biocel.2013.02.007; Fujii S, 2008, CANCER SCI, V99, P1813, DOI 10.1111/j.1349-7006.2008.00893.x; Furuta S, 2004, ONCOGENE, V23, P3898, DOI 10.1038/sj.onc.1207539; GAO X, 1995, CANCER RES, V55, P1002; Gong C, 2013, ONCOGENE, V32, P2261, DOI 10.1038/onc.2012.252; Huang SB, 2010, AUTOPHAGY, V6, P256, DOI 10.4161/auto.6.2.11124; Kang R, 2011, CELL DEATH DIFFER, V18, P571, DOI 10.1038/cdd.2010.191; Kondo Y, 2005, NAT REV CANCER, V5, P726, DOI 10.1038/nrc1692; Koneri K, 2007, ANTICANCER RES, V27, P1453; Lee JW, 2007, APMIS, V115, P750, DOI 10.1111/j.1600-0463.2007.apm_640.x; Li BX, 2009, AUTOPHAGY, V5, P303, DOI 10.4161/auto.5.3.7491; Li DD, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0045058; Liang C, 2006, NAT CELL BIOL, V8, P688, DOI 10.1038/ncb1426; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Liu JL, 2011, CELL, V147, P223, DOI 10.1016/j.cell.2011.08.037; Liu Y, 2006, P NATL ACAD SCI USA, V103, P976, DOI 10.1073/pnas.0510146103; Livesey KM, 2012, CANCER RES, V72, P1996, DOI 10.1158/0008-5472.CAN-11-2291; Maiuri MC, 2007, EMBO J, V26, P2527, DOI 10.1038/sj.emboj.7601689; Marino G, 2007, J BIOL CHEM, V282, P18573, DOI 10.1074/jbc.M701194200; Mathew R, 2007, NAT REV CANCER, V7, P961, DOI 10.1038/nrc2254; Miracco C, 2007, INT J ONCOL, V30, P429; Qu XP, 2003, J CLIN INVEST, V112, P1809, DOI 10.1172/JCI200320039; RODRIGUES NR, 1990, P NATL ACAD SCI USA, V87, P7555, DOI 10.1073/pnas.87.19.7555; Sasaki K, 2010, BMC CANCER, V10, DOI 10.1186/1471-2407-10-370; Sato K, 2007, CANCER RES, V67, P9677, DOI 10.1158/0008-5472.CAN-07-1462; Shaw RJ, 2006, NATURE, V441, P424, DOI 10.1038/nature04869; Xie CM, 2011, FREE RADICAL BIO MED, V51, P1365, DOI 10.1016/j.freeradbiomed.2011.06.016; Yang PM, 2010, CANCER RES, V70, P7699, DOI 10.1158/0008-5472.CAN-10-1626; Yang SY, 2011, ANN SURG ONCOL, V18, pS239, DOI 10.1245/s10434-011-1789-x; Yue ZY, 2003, P NATL ACAD SCI USA, V100, P15077, DOI 10.1073/pnas.2436255100; Zeng XH, 2006, J CELL SCI, V119, P259, DOI 10.1242/jcs.02735; Zhou WH, 2012, AUTOPHAGY, V8, P389, DOI 10.4161/auto.18641	37	26	30	0	9	SPRINGER	DORDRECHT	VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS	0163-2116	1573-2568		DIGEST DIS SCI	Dig. Dis. Sci.	OCT	2013	58	10					2887	2894		10.1007/s10620-013-2732-8			8	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	223BO	WOS:000324778900017	23812859	hybrid, Green Published			2022-04-25	
J	Xavier, CPR; Lima, CF; Pedro, DFN; Wilson, JM; Kristiansen, K; Pereira-Wilson, C				Xavier, Cristina P. R.; Lima, Cristovao F.; Pedro, Dalila F. N.; Wilson, Jonathan M.; Kristiansen, Karsten; Pereira-Wilson, Cristina			Ursolic acid induces cell death and modulates autophagy through JNK pathway in apoptosis-resistant colorectal cancer cells	JOURNAL OF NUTRITIONAL BIOCHEMISTRY			English	Article						Ursolic acid; Colorectal carcinoma; Cell death; Autophagy; JNK; 5-fluorouracil	N-TERMINAL KINASE; SIGNALING PATHWAYS; P53; ACTIVATION; BCL-2; PHOSPHORYLATION; INDUCTION; CHEMOTHERAPY; EXPRESSION; QUERCETIN	Colorectal carcinomas (CRCs) with P53 mutations have been shown to be resistant to chemotherapy with 5-fluorouracil (5-FU), the most widely used chemotherapeutic drug for CRC treatment. Autophagy is emerging as a promising therapeutic target for drug-resistant tumors. In the present study, we tested the effects of ursolic acid (UA), a natural triterpenoid, on cell death mechanisms and its effects in combination with 5-FU in the HCf 15 p53 mutant apoptosisresistant CRC cell line. The involvement of UA in autophagy and its in vivo efficacy were evaluated. Our data show that UA induces apoptosis independent of caspases in HCT15 cells and enhances 5-FU effects associated with an activation of c-jun N-terminal kinase (INK). In this cell line, where this compound has a more pronounced effect on the induction of cell death compared to 5-FU, apoptosis corresponds only to a small percentage of the total cell death induced by UA. UA also modulated autophagy by inducing the accumulation of LC3 and p62 levels with involvement of JNK pathway, which indicates a contribution of autophagy on JNK-dependent induction of cell death by UA. By using nude mice xenografted with HCT15 cells, we verified that UA was also active in vivo decreasing tumor growth rate. In conclusion, this study shows UA's anticancer potential both in vitro and in vivo. Induction of cell death and modulation of autophagy in CRC-resistant cells were shown to involve JNK signaling. (C) 2013 Elsevier Inc. All rights reserved.	[Xavier, Cristina P. R.; Pedro, Dalila F. N.; Pereira-Wilson, Cristina] Univ Minho, Dept Biol, CBMA Ctr Mol & Environm Biol, P-4710057 Braga, Portugal; [Lima, Cristovao F.] Univ Minho, Dept Biol, CITAB Ctr Res & Technol Agroenvironm & Biol Sci, P-4710057 Braga, Portugal; [Wilson, Jonathan M.] Univ Porto, CIMAR Associate Lab, Interdisciplinary Ctr Marine & Environm Res CIIMA, P-4050123 Oporto, Portugal; [Kristiansen, Karsten; Pereira-Wilson, Cristina] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark		Pereira-Wilson, C (corresponding author), Univ Minho, Dept Biol, CBMA Ctr Mol & Environm Biol, P-4710057 Braga, Portugal.	cpereira@bio.uminho.pt	Wilson, Jonathan/I-6071-2012; Wilson, Jonathan Mark/AAG-6481-2019; Pereira Wilson, Cristina/F-1967-2013; Xavier, Cristina Pinto Ribeiro/C-7442-2015; Kristiansen, Karsten/J-5148-2014; Lima, Cristovao/B-6123-2009	Wilson, Jonathan/0000-0003-3681-1166; Wilson, Jonathan Mark/0000-0003-3681-1166; Xavier, Cristina Pinto Ribeiro/0000-0002-4613-1917; Kristiansen, Karsten/0000-0002-6024-0917; Lima, Cristovao/0000-0003-3557-3549; Pedro, Dalila/0000-0003-1724-7504; Pereira-Wilson, Cristina/0000-0002-3714-8258	Foundation for Science and Technology (FCT), PortugalPortuguese Foundation for Science and Technology [SFRH/BD/27524/2006, SFRH/BD/64817/2009]; University of Copenhagen [SFRH/BSAB/918/2009]; FCT research grants [PTDC/QUI-BI0J101392/2008, PEst-C/BIA/U14050/2011]; QREN; European Community fund FEDEREuropean Commission	C.P.R.X. and D.F.N.P. were supported by the Foundation for Science and Technology (FCT), Portugal, through grants SFRH/BD/27524/2006 and SFRH/BD/64817/2009, respectively. C.P.W. was guest professor at University of Copenhagen through the grant SFRH/BSAB/918/2009. The work was supported by FCT research grants PTDC/QUI-BI0J101392/2008 (NaturAge) and PEst-C/BIA/U14050/2011. All projects are co-funded by the program COMPETE from QREN with co-participation from the European Community fund FEDER. We would like to thank Dr. Morten Johnsen from the Department of Biology, University of Copenhagen, for the technical assistance in the in vivo experiment.	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Nutr. Biochem.	APR	2013	24	4					706	712		10.1016/j.jnutbio.2012.04.004			7	Biochemistry & Molecular Biology; Nutrition & Dietetics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Nutrition & Dietetics	120IQ	WOS:000317164400013	22841540	Green Submitted			2022-04-25	
J	Yu, MS; Henning, R; Walker, A; Kim, G; Perroy, A; Alessandro, R; Virador, V; Kohn, EC				Yu, Minshu; Henning, Ryan; Walker, Amanda; Kim, Geoffrey; Perroy, Alyssa; Alessandro, Riccardo; Virador, Victoria; Kohn, Elise C.			L-asparaginase inhibits invasive and angiogenic activity and induces autophagy in ovarian cancer	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE			English	Article						asparaginase; ovarian cancer; sialyl Lewis X; angiogenesis; autophagy	FOCAL ADHESION KINASE; COLON-CARCINOMA CELLS; INTEGRIN GLYCOSYLATION; GLYCOPROTEIN SYNTHESIS; PREDICTIVE BIOMARKER; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; LEUKEMIA CELLS; PHASE-II; EXPRESSION	Recent work identified L-asparaginase (L-ASP) as a putative therapeutic target for ovarian cancer. We suggest that L-ASP, a dysregulator of glycosylation, would interrupt the local microenvironment, affecting the ovarian cancer cellendothelial cell interaction and thus angiogenesis without cytotoxic effects. Ovarian cancer cell lines and human microvascular endothelial cells (HMVEC) were exposed to L-ASP at physiologically attainable concentrations and subjected to analyses of endothelial tube formation, invasion, adhesion and the assessment of sialylated proteins involved in matrix-associated and heterotypic cell adhesion. Marked reduction in HMVEC tube formation in vitro, HMVEC and ovarian cancer cell invasion, and heterotypic cell-cell and cell-matrix adhesion was observed (P < 0.05-0.0001). These effects were associated with reduced binding to beta 1integrin, activation of FAK, and cell surface sialyl LewisX (sLex) expression. No reduction in HMVEC E-selectin expression was seen consistent with the unidirectional inhibitory actions observed. L-ASP concentrations were non-toxic to either ovarian cancer or HMVEC lines in the time frame of the assays. However, early changes of autophagy were observed in both cell types with induction of ATG12, beclin-1, and cleavage of LC-3, indicating cell injury did occur. These data and the known mechanism of action of L-ASP on glycosylation of nascent proteins suggest that L-ASP reduces of ovarian cancer dissemination and progression through modification of its microenvironment. The reduction of ovarian cancer cell surface sLex inhibits interaction with HMVEC and thus HMVEC differentiation into tubes, inhibits interaction with the local matrix reducing invasive behaviour, and causes cell injury initiating autophagy in tumour and vascular cells.	[Yu, Minshu; Henning, Ryan; Walker, Amanda; Kim, Geoffrey; Perroy, Alyssa; Virador, Victoria; Kohn, Elise C.] NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA; [Alessandro, Riccardo] Univ Palermo, Sez Biol & Genet, Dipartimento Biopatol & Biotecnol Med & Forensi, Palermo, Italy		Kohn, EC (corresponding author), 10 Ctr Dr,MSC 1906, Bethesda, MD 20892 USA.	ek1b@nih.gov	Virador, Victoria M./A-8173-2009		NIH, National Cancer Institute, Center for Cancer ResearchUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI); NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [ZIASC009375, ZIASC009163, ZIASC009374] Funding Source: NIH RePORTER	This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.	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Cell. Mol. Med.	OCT	2012	16	10					2369	2378		10.1111/j.1582-4934.2012.01547.x			10	Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Research & Experimental Medicine	012LK	WOS:000309237500013	22333033	Green Submitted, Green Accepted, gold, Green Published			2022-04-25	
J	Wang, WL; Zhu, DR; Chen, C; Zhu, TY; Han, C; Liu, FY; Li, LN; Luo, JG; Kong, LY				Wang, Wen-Li; Zhu, Dong-Rong; Chen, Chen; Zhu, Tian-Yu; Han, Chao; Liu, Fei-Yan; Li, Ling-Nan; Luo, Jian-Guang; Kong, Ling-Yi			Taicrypnacids A and B, a Pair of C-37 Heterodimeric Diterpenoid Stereoisomers fronn Taiwania cryptomerioides	JOURNAL OF NATURAL PRODUCTS			English	Article							DEHYDROABIETANE DERIVATIVES; OXIDATIVE STRESS; ER STRESS; APOPTOSIS; CELLS; AUTOPHAGY; MEROTERPENOIDS; CYCLOADDUCTS; ACTIVATION; PROTEASOME	Two uncommon C-37 heterodimeric diterpenoids, taicrypnacids A (1) and B (2), and a known labdane-type diterpenoid (3) were isolated from the leaves of Taiwania cryptomerioides. Several techniques, such as comprehensive spectroscopic analysis, chemical conversion, X-ray crystallography, and ECD data, were employed to define the structures. The two new compounds displayed cytotoxicity against human breast cancer (MCF-7), osteosarcoma (U-2 OS), and human colon carcinoma (HCT-116) cell lines, while the methyl ester la showed no activity. Compound 1 induced Ca2+-ROS pathway-mediated endoplasmic reticulum stress, and excessive stress led to cell death by activating apoptosis and autophagy.	[Wang, Wen-Li; Zhu, Dong-Rong; Chen, Chen; Zhu, Tian-Yu; Han, Chao; Liu, Fei-Yan; Li, Ling-Nan; Luo, Jian-Guang; Kong, Ling-Yi] China Pharmaceut Univ, Sch Tradit Chinese Pharm, Jiangsu Key Lab Bioact Nat Prod Res, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, Peoples R China; [Wang, Wen-Li; Zhu, Dong-Rong; Chen, Chen; Zhu, Tian-Yu; Han, Chao; Liu, Fei-Yan; Li, Ling-Nan; Luo, Jian-Guang; Kong, Ling-Yi] China Pharmaceut Univ, Sch Tradit Chinese Pharm, State Key Lab Nat Med, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, Peoples R China		Luo, JG; Kong, LY (corresponding author), China Pharmaceut Univ, Sch Tradit Chinese Pharm, Jiangsu Key Lab Bioact Nat Prod Res, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, Peoples R China.	luojg@cpu.edu.cn; cpu_lykong@126.com			Drug Innovation Major Project [2018ZX09735002-003]; Program for Changjiang Scholars and Innovative Research Team in UniversityProgram for Changjiang Scholars & Innovative Research Team in University (PCSIRT) [IRT_15R63]	This research was supported by the Drug Innovation Major Project (2018ZX09735002-003) and the Program for Changjiang Scholars and Innovative Research Team in University (IRT_15R63).	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Nat. Prod.	AUG	2019	82	8					2087	2093		10.1021/acs.jnatprod.8b00815			7	Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)	Plant Sciences; Pharmacology & Pharmacy	IU2UJ	WOS:000483435000003	31347365				2022-04-25	
J	Chen, YJ; Hao, Q; Wang, SS; Cao, MM; Huang, YD; Weng, XL; Wang, JQ; Zhang, Z; He, XH; Lu, H; Zhou, X				Chen, Yajie; Hao, Qian; Wang, Shanshan; Cao, Mingming; Huang, Yingdan; Weng, Xiaoling; Wang, Jieqiong; Zhang, Zhen; He, Xianghuo; Lu, Hua; Zhou, Xiang			Inactivation of the tumor suppressor p53 by long noncoding RNA RMRP	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA			English	Article						p53; long noncoding RNA; RMRP; SNRPA1; PARP inhibition	PROCESSING ENDORIBONUCLEASE; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; PARP INHIBITORS; MUTATIONS; PROTEIN; TRANSLATION; COMPONENT; RESCUE; DOMAIN	p53 inactivation is highly associated with tumorigenesis and drug resistance. Here, we identify a long noncoding RNA, the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP), as an inhibitor of p53. RMRP is overexpressed and associated with an unfavorable prognosis in colorectal cancer. Ectopic RMRP suppresses p53 activity by promoting MDM2-induced p53 ubiquitination and degradation, while depletion of RMRP activates the p53 pathway. RMRP also promotes colorectal cancer growth and proliferation in a p53-dependent fashion in vitro and in vivo. This anti-p53 action of RMRP is executed through an identified partner protein, SNRPA1. RMRP can interact with SNRPA1 and sequester it in the nucleus, consequently blocking its lysosomal proteolysis via chaperone-mediated autophagy. The nuclear SNRPA1 then interacts with p53 and enhances MDM2-induced proteasomal degradation of p53. Remarkably, ablation of SNRPA1 completely abrogates RMRP regulation of p53 and tumor cell growth, indicating that SNRPA1 is indispensable for the anti-p53 function of RMRP. Interestingly and significantly, poly (ADP-ribose) polymerase (PARP) inhibitors induce RMRP expression through the transcription factor C/EBPI3, and RMRP confers tumor resistance to PARP inhibition by preventing p53 activation. Altogether, our study demonstrates that RMRP plays an oncogenic role by inactivating p53 via SNRPA1 in colorectal cancer.	[Chen, Yajie; Hao, Qian; Wang, Shanshan; Cao, Mingming; Huang, Yingdan; Weng, Xiaoling; He, Xianghuo; Zhou, Xiang] Fudan Univ, Shanghai Canc Ctr, Shanghai 200032, Peoples R China; [Chen, Yajie; Hao, Qian; Wang, Shanshan; Cao, Mingming; Huang, Yingdan; Weng, Xiaoling; He, Xianghuo; Zhou, Xiang] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China; [Chen, Yajie; Hao, Qian; Wang, Shanshan; Cao, Mingming; Huang, Yingdan; Weng, Xiaoling; He, Xianghuo; Zhou, Xiang] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China; [Chen, Yajie; Zhang, Zhen] Fudan Univ, Shanghai Canc Ctr, Dept Radiat Oncol, Shanghai 200032, Peoples R China; [Wang, Jieqiong; Lu, Hua] Tulane Univ, Dept Biochem & Mol Biol, Sch Med, New Orleans, LA 70112 USA; [Wang, Jieqiong; Lu, Hua] Tulane Univ, Tulane Canc Ctr, Sch Med, New Orleans, LA 70112 USA; [He, Xianghuo; Zhou, Xiang] Fudan Univ, Shanghai Canc Ctr, Key Lab Breast Canc Shanghai, Shanghai 200032, Peoples R China; [Zhou, Xiang] Fudan Univ, Minist Sci & Technol Inst Biomed Sci, Shanghai Key Lab Med Epigenet, Int Colab Med Epigenet & Metab, Shanghai 200032, Peoples R China		Hao, Q; Zhou, X (corresponding author), Fudan Univ, Shanghai Canc Ctr, Shanghai 200032, Peoples R China.; Hao, Q; Zhou, X (corresponding author), Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China.; Hao, Q; Zhou, X (corresponding author), Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China.; Zhou, X (corresponding author), Fudan Univ, Shanghai Canc Ctr, Key Lab Breast Canc Shanghai, Shanghai 200032, Peoples R China.; Zhou, X (corresponding author), Fudan Univ, Minist Sci & Technol Inst Biomed Sci, Shanghai Key Lab Med Epigenet, Int Colab Med Epigenet & Metab, Shanghai 200032, Peoples R China.	qhao15@hotmail.com; xiangzhou@fudan.edu.cn	He, Xianghuo/I-1497-2014; Zhou, Xiang/J-5046-2017	He, Xianghuo/0000-0001-8872-668X; Zhou, Xiang/0000-0002-1172-7948; Wang, Shanshan/0000-0002-6651-2821	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81702352]; Reynolds and Ryan Families Chair Fund of Translational Cancer	We thank the laboratory members for active and helpful discussion, Yazhen Gui for laboratory assistance, Ping Zhang for flow cytometry, and the innovative research team of the high-level local univer-sity in Shanghai. X.Z. was supported by the National Natural Science Foundation of China (Grants 81874053 and 82072879) , Q.H. was supported by the National Natural Science Foundation of China (Grant 81702352) , and H.L. was supported by the Reynolds and Ryan Families Chair Fund of Translational Cancer.	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Natl. Acad. Sci. U. S. A.	JUL 20	2021	118	29							e2026813118	10.1073/pnas.2026813118			12	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	UA3BQ	WOS:000685037700013	34266953	hybrid, Green Published			2022-04-25	
J	Yang, XD; Xu, XH; Zhu, JJ; Zhang, SY; Wu, Y; Wu, YY; Zhao, K; Xing, CG; Cao, JP; Zhu, H; Li, M; Ye, ZY; Peng, W				Yang, Xiaodong; Xu, Xiaohui; Zhu, Junjia; Zhang, Shuyu; Wu, Yong; Wu, Yongyou; Zhao, Kui; Xing, Chungen; Cao, Jianping; Zhu, Hong; Li, Ming; Ye, Zhenyu; Peng, Wei			miR-31 affects colorectal cancer cells by inhibiting autophagy in cancer-associated fibroblasts	ONCOTARGET			English	Article						miR-31; colorectal cancer; CAFs; autophagy; biological behaviors	EXPRESSION PROFILES; TUMOR-GROWTH; MICRORNA-31; GLYCOLYSIS; METASTASIS; SENESCENCE; SURVIVAL; STAGE	Autophagy is a double-edged sword in tumor development. Recent studies have found that miRNAs have an inhibitory effect on the regulation of autophagy. It has been reported that miR-31 plays an important role in the development of colorectal cancer. However, what role miR-31 plays in colorectal cancer-associated fibroblasts (CAFs) has not been determined. In this study, we confirmed that the expression of miR-31 in CAFs was higher than in normal colorectal fibroblasts (NFs). We also found that treatment of CAFs with miR-31 mimic inhibited the expression of the autophagy-related genes Beclin-1, ATG, DRAM and LC3. In addition, we found up-regulation of miR-31 significantly affected colorectal cancer cell behaviors, including proliferation, invasion and apoptosis. Also, up-regulation of miR-31 in CAF could increase the radiosensitivity of colorectal cancer cells co-cultured with CAF. In summary, miR-31 can inhibit autophagy in colorectal CAFs, affect colorectal cancer development, and increase the radiosensitivity of colorectal cancer cells co-cultured with CAF. We hypothesize that miR-31 may become a new target of treatments for colorectal cancer.	[Yang, Xiaodong; Xu, Xiaohui; Zhu, Junjia; Wu, Yong; Wu, Yongyou; Zhao, Kui; Xing, Chungen; Ye, Zhenyu; Peng, Wei] Soochow Univ, Affiliated Hosp 2, Dept Gen Surg, Suzhou 215004, Peoples R China; [Xu, Xiaohui] Soochow Univ, Peoples Hosp Taicang City 1, Dept Gen Surg, Taicang Affiliated Hosp, Suzhou 215400, Peoples R China; [Zhang, Shuyu; Cao, Jianping; Li, Ming] Soochow Univ, Coll Med, Sch Radiat Med & Protect, Suzhou 215123, Peoples R China; [Zhu, Hong] Soochow Univ, Affiliated Hosp 1, Oncol Dept, Suzhou 215006, Peoples R China		Xing, CG (corresponding author), Soochow Univ, Affiliated Hosp 2, Dept Gen Surg, Suzhou 215004, Peoples R China.; Cao, JP (corresponding author), Soochow Univ, Coll Med, Sch Radiat Med & Protect, Suzhou 215123, Peoples R China.	xingcg@126.com; jpcao@suda.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672970, 81301933, 81472917, 81572345]; Health Research Projects in Jiangsu Province [H201313]; Suzhou Technology Bureau [SYSD2013090, SYS201552, SYSD2015034]; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); Suzhou Science and Education health youth projects [kjxw2015050]; Taicang Municipal Science and Technology Bureau of Basic Research Program [TC2015YYYL01]; focus of clinical disease treatment technology special funds of Suzhou city [LCZX201505]; Soochow university	This work was partially supported by the National Natural Science Foundation of China (Grant No: 81672970, 81301933, 81472917 and 81572345), Health Research Projects in Jiangsu Province (H201313), the projects of Suzhou Technology Bureau (SYSD2013090, SYS201552, SYSD2015034) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Suzhou Science and Education health youth projects (kjxw2015050), Taicang Municipal Science and Technology Bureau of Basic Research Program (TC2015YYYL01), the focus of clinical disease treatment technology special funds of Suzhou city (LCZX201505), and the second affiliated hospital of Soochow university preponderant clinic discipline group project funding.	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J	Wei, FJ; Wang, YM; Luo, ZW; Li, Y; Duan, YX				Wei, Fujing; Wang, Yimin; Luo, Zewei; Li, Yu; Duan, Yixiang			New findings of silica nanoparticles induced ER autophagy in human colon cancer cell	SCIENTIFIC REPORTS			English	Article							SIZE-DEPENDENT CYTOTOXICITY; SELECTIVE AUTOPHAGY; ENDOPLASMIC-RETICULUM; IN-VITRO; PROTEIN; COMPARTMENTS; MATURATION; INDUCTION; PATHWAY; LC3	Nanoparticle-induced autophagy has been extensively studied, however, real time information about the endoplasmic reticulum involved autophagic process (ER autophagy) induced by nanomaterials remains unknown. In this work, silica nanoparticles (SNPs) were synthesized with characteristics of low toxicity, good biocompatibility and excellent water dispersibility to treat cells. Results show that either low concentration (10 mu g/mL) or high concentration (200 mu g/mL) of SNPs could increase the quantity of processing from microtubule-associated protein 1-light chain 3-I (LC3-I) to the other variant of LC3 (LC3-II). Interestingly, the level of autophagy induced by the SNPs is associated with the treated time but not the concentrations of SNPs. Importantly, for the first time, SNP accumulation in ER was discovered through co-localization analysis, which incurs ER autophagy. These new findings about SNPs-induced ER autophagy could open an effective way for securely designing silica-based nanoparticles and enable us to know more about ER autophagy.	[Wei, Fujing; Wang, Yimin; Luo, Zewei; Li, Yu; Duan, Yixiang] Sichuan Univ, Coll Life Sci, Res Ctr Analyt Instrumentat, Key Lab Bioresource & Ecoenvironm,Minist Educ, Chengdu 610065, Peoples R China		Duan, YX (corresponding author), Sichuan Univ, Coll Life Sci, Res Ctr Analyt Instrumentat, Key Lab Bioresource & Ecoenvironm,Minist Educ, Chengdu 610065, Peoples R China.	yduan@scu.edu.cn		Luo, Zewei/0000-0001-9178-9868			Ay F, 2004, OPT MATER, V26, P33, DOI 10.1016/j.optmat.2003.12.004; Bernales S, 2007, AUTOPHAGY, V3, P285, DOI 10.4161/auto.3930; Biazik J, 2015, AUTOPHAGY, V11, P439, DOI 10.1080/15548627.2015.1017178; Eskelinen EL, 2005, AUTOPHAGY, V1, P1, DOI 10.4161/auto.1.1.1270; Ge L, 2013, ELIFE, V2, DOI 10.7554/eLife.00947; Graef M, 2013, MOL BIOL CELL, V24, P2918, DOI 10.1091/mbc.E13-07-0381; Guo SJ, 2015, AUTOPHAGY, V11, P560, DOI 10.1080/15548627.2015.1017181; Ha SW, 2014, ACS NANO, V8, P5898, DOI 10.1021/nn5009879; Hamasaki M, 2003, CELL STRUCT FUNCT, V28, P49; Hasegawa J, 2015, METHODS, V75, P128, DOI 10.1016/j.ymeth.2014.12.014; Huang YC, 2013, ANGEW CHEM INT EDIT, V52, P4858, DOI 10.1002/anie.201209523; Hwang AA, 2015, SMALL, V11, P319, DOI 10.1002/smll.201400765; Itakura E, 2011, J CELL BIOL, V192, P17, DOI 10.1083/jcb.201009067; Ivanov Andrei I., 2008, V440, P15, DOI 10.1007/978-1-59745-178-9_2; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; Khaminets A, 2015, NATURE, V522, P354, DOI 10.1038/nature14498; Kim IY, 2015, NANOMED-NANOTECHNOL, V11, P1407, DOI 10.1016/j.nano.2015.03.004; Kimura S, 2007, AUTOPHAGY, V3, P452, DOI 10.4161/auto.4451; Klionsky DJ, 2012, AUTOPHAGY, V8, P445, DOI 10.4161/auto.19496; Lajoie P, 2010, INT REV CEL MOL BIO, V282, P135, DOI 10.1016/S1937-6448(10)82003-9; LANGKOPF A, 1992, J BIOL CHEM, V267, P16561; Le Roy C, 2005, NAT REV MOL CELL BIO, V6, P112, DOI 10.1038/nrm1571; Lemus L, 2016, CELL REP, V14, P1710, DOI 10.1016/j.celrep.2016.01.047; Li Y, 2011, TOXICOL IN VITRO, V25, P1343, DOI 10.1016/j.tiv.2011.05.003; Lim JP, 2011, IMMUNOL CELL BIOL, V89, P836, DOI 10.1038/icb.2011.20; Lipatova Z, 2015, PLOS GENET, V11, DOI 10.1371/journal.pgen.1005390; Lipatova Z, 2013, MOL BIOL CELL, V24, P3133, DOI 10.1091/mbc.E13-05-0269; Lu X, 2011, INT J NANOMED, V6, P1889, DOI 10.2147/IJN.S24005; Mathew R, 2009, CELL, V137, P1062, DOI 10.1016/j.cell.2009.03.048; Mochida K, 2015, NATURE, V522, P359, DOI 10.1038/nature14506; Napierska D, 2009, SMALL, V5, P846, DOI 10.1002/smll.200800461; Oshima R, 2016, SCI REP-UK, V6, DOI 10.1038/srep24997; Pasqua L, 2009, CURR MED CHEM, V16, P3054, DOI 10.2174/092986709788803079; Rashid HO, 2015, AUTOPHAGY, V11, P1956, DOI 10.1080/15548627.2015.1091141; Roggers R, 2014, AAPS PHARMSCITECH, V15, P1163, DOI 10.1208/s12249-014-0142-7; Ryter SW, 2013, MOL CELLS, V36, P7, DOI 10.1007/s10059-013-0140-8; Schutz I, 2016, J BIOL CHEM, V291, P14170, DOI 10.1074/jbc.M115.710947; STOBER W, 1968, J COLLOID INTERF SCI, V26, P62, DOI 10.1016/0021-9797(68)90272-5; Stolz A, 2014, NAT CELL BIOL, V16, P495, DOI 10.1038/ncb2979; Su YC, 2016, INT J NEUROSCI, V126, P681, DOI 10.3109/00207454.2015.1059836; Teng RJ, 2012, AM J PHYSIOL-LUNG C, V302, P1651, DOI 10.1152/ajplung.00177.2011; Thomassen LCJ, 2010, LANGMUIR, V26, P328, DOI 10.1021/la902050k; van der Vaart A, 2008, TRAFFIC, V9, P281, DOI 10.1111/j.1600-0854.2007.00674.x; Wang W, 2003, J PHYS CHEM B, V107, P3400, DOI 10.1021/jp0221800; Wrighton Katharine H, 2015, Nat Rev Mol Cell Biol, V16, P389, DOI 10.1038/nrm4013; Xi C, 2016, INFLAMM RES, V65, P325, DOI 10.1007/s00011-016-0919-0; Yu JC, 2016, NANOSCALE, V8, P9178, DOI 10.1039/c5nr08895j; Zhang X., 2016, NANOSCALE; Zhang XD, 2014, BIOMATERIALS, V35, P1932, DOI 10.1016/j.biomaterials.2013.10.034; Zhou Y, 2016, ACS APPL MATER INTER, V8, P6423, DOI 10.1021/acsami.6b01031	50	26	26	4	52	NATURE PUBLISHING GROUP	LONDON	MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND	2045-2322			SCI REP-UK	Sci Rep	FEB 14	2017	7								42591	10.1038/srep42591			11	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	EK3ZR	WOS:000393867400001	28195184	Green Published, gold			2022-04-25	
J	Suhaimi, SA; Hong, SL; Malek, SNA				Suhaimi, Shafinah Ahmad; Hong, Sok Lai; Malek, Sri Nurestri Abdul			Rutamarin, an Active Constituent from Ruta angustifolia Pers., Induced Apoptotic Cell Death in the HT29 Colon Adenocarcinoma Cell Line	PHARMACOGNOSY MAGAZINE			English	Article						Apoptosis; cancer; cytotoxicity; in vitro; Ruta angustifolia; rutamarin	GROWTH-INHIBITION; CYCLE ARREST; CANCER; GRAVEOLENS; COUMARINS; AUTOPHAGY; PATHWAYS	Background: Ruta angustifolia Pers. is a perennial herb that is cultivated worldwide, including Southeast Asia, for the treatment of various diseases as traditional medicine. Objective: The purpose of the study was to identify an active principle of R. angustifolia and to investigate its effect on the HT29 cell death. Materials and Methods: The methanol and fractionated extracts (hexane, chloroform, ethyl acetate, and water) of R. angustifolia Pers. were initially investigated for their cytotoxic activity against two human carcinoma cell lines (MCF7 and HT29) and a normal human colon fibroblast cell line (CCD-18Co) using sulforhodamine B cytotoxicity assay. Eight compounds including rutamarin were isolated from the active chloroform extract and evaluated for their cytotoxic activity against HT29 human colon carcinoma cell line and CCD-18Co noncancer cells. Further studies on the induction of apoptosis such as morphological examinations, biochemical analyses, cell cycle analysis, and caspase activation assay were conducted in rutamarin-treated HT29 cells. Results: Rutamarin exhibited remarkable cytotoxic activity against HT29 cells (IC., value of 5.6 mu M) but was not toxic to CCD-18Co cells. The morphological and biochemical hallmarks of apoptosis including activation of caspases 3, 8, and 9 were observed in rutamarin-treated HT29 cells. These may be associated with cell cycle arrest at the GO/GI and G2/M checkpoints, which was also observed in HT29 cells. Conclusions: The present study describes rutamarin-induced apoptosis in the HT29 cell line for the first time and suggests that rutamarin has the potential to be developed as an anticancer agent.	[Suhaimi, Shafinah Ahmad; Malek, Sri Nurestri Abdul] Univ Malaya, Fac Sci, Inst Biol Sci, Kuala Lumpur 50603, Malaysia; [Hong, Sok Lai] Univ Malaya, Inst Res Management & Monitoring, Ctr Res Serv, Res Management & Innovat Complex, Kuala Lumpur 50603, Malaysia		Malek, SNA (corresponding author), Univ Malaya, Fac Sci, Inst Biol Sci, Kuala Lumpur 50603, Malaysia.	srimalek@yahoo.com	Malek, Sri Nurestri Abd/B-9834-2010; Malek, Sri Nurestri/W-8556-2019; Hong, Sok Lai/H-9892-2013	Malek, Sri Nurestri Abd/0000-0001-6278-8559; Malek, Sri Nurestri/0000-0001-6278-8559; Hong, Sok Lai/0000-0003-0721-4012; Ahmad Suhaimi, Shafinah/0000-0002-2727-3231	High Impact Research MoE from Ministry of Education Malaysia [UM.C/625/1/HIR/MoE/SC/02]; Ministry of Education Malaysia; Universiti Sains Malaysia (USM)Universiti Sains Malaysia	The research is supported by the High Impact Research MoE Grant UM.C/625/1/HIR/MoE/SC/02 from the Ministry of Education Malaysia. 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Mag.	APR-JUN	2017	13	50		2			S179	S188	PMID 28808378	10.4103/pm.pm_432_16			10	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	FK7RG	WOS:000413704300004	28808378	Green Published			2022-04-25	
J	Kim, SH; Kim, H				Kim, Suhn Hyung; Kim, Hyeyoung			Astaxanthin Modulation of Signaling Pathways That Regulate Autophagy	MARINE DRUGS			English	Review						AMP activated protein kinase (AMPK); autophagy; astaxanthin; cellular homolog of murine thymoma virus akt8 oncogene (Akt); mitogen-activated protein kinases (MAPK); c-Jun N-terminal kinase (JNK); p38	ACTIVATED PROTEIN-KINASE; ENDOPLASMIC-RETICULUM STRESS; N-TERMINAL KINASE; OXIDATIVE STRESS; CELL-DEATH; UP-REGULATION; INDUCED CYTOTOXICITY; INDUCED APOPTOSIS; TUMOR-SUPPRESSOR; COLON-CANCER	Autophagy is a lysosomal pathway that degrades and recycles unused or dysfunctional cell components as well as toxic cytosolic materials. Basal autophagy favors cell survival. However, the aberrant regulation of autophagy can promote pathological conditions. The autophagy pathway is regulated by several cell-stress and cell-survival signaling pathways that can be targeted for the purpose of disease control. In experimental models of disease, the carotenoid astaxanthin has been shown to modulate autophagy by regulating signaling pathways, including the AMP-activated protein kinase (AMPK), cellular homolog of murine thymoma virus akt8 oncogene (Akt), and mitogen-activated protein kinase (MAPK), such as c-Jun N-terminal kinase (JNK) and p38. Astaxanthin is a promising therapeutic agent for the treatment of a wide variety of diseases by regulating autophagy.	[Kim, Suhn Hyung; Kim, Hyeyoung] Yonsei Univ, Coll Human Ecol, Brain Korea 21 PLUS Project, Dept Food & Nutr, Seoul 03722, South Korea		Kim, H (corresponding author), Yonsei Univ, Coll Human Ecol, Brain Korea 21 PLUS Project, Dept Food & Nutr, Seoul 03722, South Korea.	cigdoli2@naver.com; kim626@yonsei.ac.kr		Kim, Hyeyoung/0000-0002-7019-917X	National Research Foundation (NRF) of Korea - Korean Government [NRF-2018 R1A2A2A01004855]	This study was supported financially by a grant from the National Research Foundation (NRF) of Korea, which is funded by the Korean Government (NRF-2018 R1A2A2A01004855).	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Zhang XS, 2014, MAR DRUGS, V12, P4291, DOI 10.3390/md12084291; Zhong Y, 2009, NAT CELL BIOL, V11, P468, DOI 10.1038/ncb1854	135	16	18	5	13	MDPI	BASEL	ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND		1660-3397		MAR DRUGS	Mar. Drugs	OCT	2019	17	10							546	10.3390/md17100546			22	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	JP1XI	WOS:000498064500006	31547619	Green Published, gold			2022-04-25	
J	Xu, W; Yu, MH; Qin, J; Luo, Y; Zhong, M				Xu, Wei; Yu, Minhao; Qin, Jun; Luo, Yang; Zhong, Ming			LACTB Regulates PIK3R3 to Promote Autophagy and Inhibit EMT and Proliferation Through the PI3K/AKT/mTOR Signaling Pathway in Colorectal Cancer	CANCER MANAGEMENT AND RESEARCH			English	Article						colorectal cancer; LACTB; PIK3R3; EMT; proliferation; autophagy	RETINAL-PIGMENT EPITHELIUM; CELL-CYCLE ARREST; MESENCHYMAL TRANSITION; THERAPEUTIC TARGET; ACTIVATION; CARCINOMA; APOPTOSIS; EXPRESSION; MIGRATION; PROTEIN	Background: Colorectal cancer (CRC) is one of the most common aggressive malignancies. LACTB functions as a tumor suppressor, and previous findings have demonstrated that LACTB can inhibit epithelial-to-mesenchymal transition (EMT) and proliferation of breast cancer and CRC cells. However, few studies have investigated the roles of LACTB in autophagy and proliferation in CRC. The current study aimed to identify the roles of LACTB in EMT and proliferation associated with autophagy in CRC and to elucidate the probable molecular mechanisms through which LACTB are involved in these processes. Materials and Methods: Transwell invasion, MTT, transmission electron microscopy, RNA-seq, immunoprecipitation, immunohistochemistry and Western blotting assays were performed to evaluate the migratory, invasive, proliferative and autophagic abilities of CRC cells, and the levels of active molecules involved in PI3K/AKT signaling were examined through Western blotting analysis. In addition, the in vivo function of LACTB was assessed using a tumor xenograft model. Results: Weaker LACTB expression was found in CRC tissue samples than in nonmalignant tissue samples, and LACTB inhibited cell invasion, migration, and proliferation by promoting autophagy in vitro. Furthermore, the regulatory effects of LACTB on autophagy and EMT were partially attributed to the PI3K/AKT signaling pathway. The in vivo results also showed that LACTB modulated CRC tumorigenesis. Conclusion: LACTB can regulate the activity of PIK3R3 to influence the level of PI3K, and it also promotes autophagy and inhibits EMT and proliferation in part through the PI3K/AKT/mTOR signaling pathway.	[Xu, Wei; Yu, Minhao; Qin, Jun; Luo, Yang; Zhong, Ming] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Gastrointestinal Surg, Shanghai 200127, Peoples R China		Zhong, M (corresponding author), Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Gastrointestinal Surg, Shanghai 200127, Peoples R China.	drzhongming1966@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81860435, 81873555, 81672347]	This work was supported by grants from the National Natural Science Foundation of China (grant numbers 81860435, 81873555, and 81672347).	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Res.		2020	12						5181	5200		10.2147/CMAR.S250661			20	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	MJ7NK	WOS:000548274500003	32636680	gold, Green Published			2022-04-25	
J	Zhang, HG; Wang, FJ; Wang, Y; Zhao, ZX; Qiao, PF				Zhang, Hao-Gang; Wang, Fu-Jing; Wang, Yao; Zhao, Zi-Xing; Qiao, Peng-Fei			lncRNA GAS5 inhibits malignant progression by regulating macroautophagy and forms a negative feedback regulatory loop with the miR-34a/mTOR/SIRT1 pathway in colorectal cancer	ONCOLOGY REPORTS			English	Article						colorectal cancer; lncRNA GAS5; macroautophagy; miR-34a; negative feedback regulatory loop	NONCODING RNA GAS5; TUMOR-SUPPRESSOR; AUTOPHAGY; METASTASIS; EXPRESSION; RESISTANCE; ACTIVATION; APOPTOSIS; PROMOTES; CELLS	Long non-coding RNA growth arrest specific 5 (GAS5) exerts inhibitory effects through the modulation of several target microRNAs (miRs) in cancer. However, its potential roles and underlying relationship during colorectal cancer (CRC) progression are unclear. Therefore, we explored the role of the negative feedback loop formed by the GAS5/miR-34a axis and mammalian target of rapamycin/sirtuin 1 (mTOR/SIRT1) pathway on macroautophagy and apoptosis in CRC. Expression of GAS5, miR-34a, SIRT1 and mTOR in CRC patients and cell lines was detected by quantitative reverse transcription polymerase chain reaction. Online bioinformatic analysis was used to predict the downstream miRs of GAS5. Luciferase assay and western blotting were performed to demonstrate miR-34a as a downstream target gene of GAS5 in CRC cells. The effects of the GAS5/miR-34a axis on apoptosis, macroautophagy, and the mTOR/SIRT1 pathway were assessed by flow cytometry, transmission electron microscopy and western blotting, respectively. Our results suggested that GAS5 was downregulated and acted as a molecular sponge of miR-34a during CRC progression. miR-34a participated in regulating GAS5-suppressed CRC cell macroautophagy and induced apoptosis through the mTOR/SIRT1 pathway. GAS5-mediated macroautophagy was maintained in an equilibrium state that might have a protective effect on CRC cell apoptosis. The mTOR signaling pathway suppressed GAS5 expression and formed a negative regulation feedback loop with miR-34a in CRC cells. Our results suggested that the GAS5/miR-34a/SIRT1/mTOR negative regulatory feedback loop mediated CRC cell macroautophagy, and maintained the cells in an autonomous equilibrium state, but not excessive activation state, which functions as a strong antiapoptotic phenotype during human CRC progression.	[Zhang, Hao-Gang; Wang, Fu-Jing; Wang, Yao; Zhao, Zi-Xing; Qiao, Peng-Fei] Harbin Med Univ, Affiliated Hosp 2, Dept Gen Surg, 246 Xuefu Rd, Harbin 150001, Heilongjiang, Peoples R China		Qiao, PF (corresponding author), Harbin Med Univ, Affiliated Hosp 2, Dept Gen Surg, 246 Xuefu Rd, Harbin 150001, Heilongjiang, Peoples R China.	lunwenqpf@126.com			Science Foundation of the Health Commission of Heilongjiang Province [2018346]	The present study was supported by The Science Foundation of the Health Commission of Heilongjiang Province (2018346).	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Rep.	JAN	2021	45	1					202	216		10.3892/or.2020.7825			15	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	PF0LU	WOS:000598757000019	33416133	hybrid, Green Published			2022-04-25	
J	Zhu, CL; Liu, F; Qian, WB; Zhang, TY; Li, F				Zhu, Changlai; Liu, Fang; Qian, Wenbo; Zhang, Tianyi; Li, Feng			Combined Effect of Sodium Selenite and Ginsenoside Rh2 on HCT116 Human Colorectal Carcinoma Cells	ARCHIVES OF IRANIAN MEDICINE			English	Article						Colorectal carcinoma; ginsenoside-Rh2; sodiumselenite; synergistic effect	CANCER PREVENTION; APOPTOSIS; AUTOPHAGY; BAX; ACTIVATION; BCL-2; MECHANISMS; INDUCTION; DISEASE; CYCLE	Background: Sodium selenite and ginsenoside Rh2 (G-Rh2) are well known for their anticancer properties and have been exploited as a new therapeutic approach. In this study, we are interested to evaluate if sodium selenite and G-Rh2 combination results in a synergistic anticancer effect that could contribute to lower systemic toxicity. Methods: We observed the synergistic antitumor effect by combination of sodium selenite and G-Rh2 on HCT-116 human colorectal carcinoma cells in vitro. Cell growth, viability, cell cycle progression and cell apoptosis, Bax/Bc12 ratio, caspase-3 expression, reactive oxygen species (ROS) production and autophagy were evaluated. Results: The results showed that sodium selenite and G-Rh2 combination have a synergistic effect on cell growth inhibition (57%) compared with sodium selenite (25%) and G-Rh2 alone (28%) after 24 hours of treatment. This combination also induced G1 and S phase arrest simultaneously and increased apoptosis rate. The results also indicated that Bax/Bc12 ratio and caspase-3 expression, known as proapoptotic factors, were increased in the presence of sodium selenite and G-Rh2 alone. However, combined drug treatment results in a more significant increase in Bax/Bc12 ratio and caspase-3 expression (P < 0.05). In addition, this combination significantly induces a depletion of ROS production and autophagy, compared to control, sodium selenite and G-Rh2 alone (P < 0.05). Conclusion: Sodium selenite and ginsenoside Rh2 combination may be a more effective treatment for human colorectal carcinoma and is a promising chemotherapeutic approach for malignant tumors.	[Zhu, Changlai; Liu, Fang] Nantong Univ, Coinnovat Ctr Neuroregenerat, Jiangsu Key Lab Neuroregenerat, Nantong, Jiangsu, Peoples R China; [Qian, Wenbo; Zhang, Tianyi] Nantong Univ, Coll Med, Nantong, Jiangsu, Peoples R China; [Li, Feng] Nantong Univ, Affiliated Hosp, Dept Gastroenterol, 20 Xisi Rd, Nantong 226001, Jiangsu, Peoples R China		Li, F (corresponding author), Nantong Univ, Affiliated Hosp, Dept Gastroenterol, 20 Xisi Rd, Nantong 226001, Jiangsu, Peoples R China.	willim118@hotmail.com			Scientific and Technical Development Program of Nanton [K2010018]	This study was supported by Scientific and Technical Development Program of Nanton (Grant No. K2010018).	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Iran. Med.	JAN	2016	19	1					23	29					7	Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	General & Internal Medicine	DC9LK	WOS:000369542900003	26702744				2022-04-25	
J	Tyciakova, S; Valova, V; Svitkova, B; Matuskova, M				Tyciakova, Silvia; Valova, Valeria; Svitkova, Barbora; Matuskova, Miroslava			Overexpression of TNF alpha induces senescence, autophagy and mitochondrial dysfunctions in melanoma cells	BMC CANCER			English	Article						TNF alpha; Melanoma; Senescence; Autophagy; Aldehyde dehydrogenase activity; Mitochondrial status; Cancer stem cell-related markers	TUMOR-NECROSIS-FACTOR; CANCER STEM-CELLS	BackgroundTumor necrosis factor alpha (TNF alpha) is a pleiotropic cytokine with both anti-tumorigenic and pro-tumorigenic activity, affecting tumor cell biology, the balance between cell survival and death. The final effect of TNF alpha is dependent on the type of malignant cells, with the potential to arrest cancer progression.MethodsIn order to explain the diverse cellular response to TNF alpha, we engineered melanoma and colorectal carcinoma cell lines stably overexpressing this cytokine.ResultsUnder the TNF alpha overexpression, significant upregulation of two genes was observed: proinflammatory cytokine IL6 gene in melanoma cells A375 and gene for pro-apoptotic ligand TRAIL in colorectal carcinoma cells HT29, both mediated by TNF alpha /TNFR1 signaling. Malignant melanoma line A375 displayed also increased autophagy on day 3, followed by premature senescence on day 6. Both processes seem to be interconnected, following earlier apoptosis induction and deregulation of mitochondrial functions. We documented altered mitochondrial status, lowered ATP production, lowered mitochondrial mass, and changes in mitochondrial morphology (shortened and condensed mitochondria) both in melanoma and colorectal carcinoma cells. Overexpression of TNF alpha was not linked with significant affection of the subpopulation of cancer stem-like cells in vitro. However, we could demonstrate a decrease in aldehyde dehydrogenase (ALDH) activity up to 50%, which is associated with to the stemness phenotype.ConclusionsOur in vitro study of direct TNF alpha influence demonstrates two distinct outcomes in tumor cells of different origin, in non-epithelial malignant melanoma cells of neural crest origin, and in colorectal carcinoma cells derived from the epithelium.	[Tyciakova, Silvia; Valova, Valeria; Svitkova, Barbora; Matuskova, Miroslava] Slovak Acad Sci, Biomed Res Ctr, Canc Res Inst, Dubravska Cesta 9, Bratislava 84505, Slovakia; [Valova, Valeria] Comenius Univ, Dept Genet, Fac Nat Sci, Ilkovicova 6, Bratislava 84215, Slovakia		Tyciakova, S (corresponding author), Slovak Acad Sci, Biomed Res Ctr, Canc Res Inst, Dubravska Cesta 9, Bratislava 84505, Slovakia.	silvia.tyciakova@savba.sk	Svitkova, Barbora/AAV-9228-2020; Tyciakova, Silvia/F-7089-2018	Tyciakova, Silvia/0000-0003-2919-0410; Svitkova (Buliakova), Barbora/0000-0001-8927-3934	VEGAVedecka grantova agentura MSVVaS SR a SAV (VEGA)European Commission [02/178/17, 02/0050/19]; Ministry of Health of the Slovak Republic [2019/60-BMCSAV-4]; EU Horizon 2020 Research and Innovation programme [857381]; UVP BIOMED [ITMS 26240220087]; Slovak Cancer Research Foundation [RFL2009, RFL2012]	This work was supported by VEGA grants no. 02/178/17, 02/0050/19; by Ministry of Health of the Slovak Republic under the project registration number 2019/60-BMCSAV-4, EU Horizon 2020 Research and Innovation programme under grant agreement No 857381 (VISION), by UVP BIOMED - project ITMS 26240220087 and by Slovak Cancer Research Foundation RFL2009 and RFL2012 programs. The funding did not affect the design of the study, collection, analysis or interpretation of data or preparation of the manuscript.	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J	Yang, Z; Liang, SQ; Saliakoura, M; Yang, HT; Vassella, E; Konstantinidou, G; Tschan, M; Hegedus, B; Zhao, L; Gao, YY; Xu, D; Deng, HB; Marti, TM; Kocher, GJ; Wang, WX; Schmid, RA; Peng, RW				Yang, Zhang; Liang, Shun-Qing; Saliakoura, Maria; Yang, Haitang; Vassella, Eric; Konstantinidou, Georgia; Tschan, Mario; Hegedus, Balazs; Zhao, Liang; Gao, Yanyun; Xu, Duo; Deng, Haibin; Marti, Thomas M.; Kocher, Gregor J.; Wang, Wenxiang; Schmid, Ralph A.; Peng, Ren-Wang			Synergistic effects of FGFR1 and PLK1 inhibitors target a metabolic liability in KRAS-mutant cancer	EMBO MOLECULAR MEDICINE			English	Article						autophagy; fibroblast growth factor receptor 1; KRAS-mutant cancer; polo-like kinase 1; synthetic lethal vulnerability	NON-ONCOGENE ADDICTION; CELL LUNG-CANCER; KINASE INHIBITOR; AUTOPHAGY; THERAPY; GROWTH; PHOSPHORYLATION; VULNERABILITIES; PROGRESSION; MUTATIONS	KRAS oncoprotein is commonly mutated in human cancer, but effective therapies specifically targeting KRAS-driven tumors remain elusive. Here, we show that combined treatment with fibroblast growth factor receptor 1 (FGFR1) and polo-like kinase 1 (PLK1) inhibitors evoke synergistic cytotoxicity in KRAS-mutant tumor models in vitro and in vivo. Pharmacological and genetic suppression of FGFR1 and PLK1 synergizes to enhance anti-proliferative effects and cell death in KRAS-mutant lung and pancreatic but not colon nor KRAS wild-type cancer cells. Mechanistically, co-targeting FGFR1 and PLK1 upregulates reactive oxygen species (ROS), leading to oxidative stress-activated c-Jun N-terminal kinase (JNK)/p38 pathway and E2F1-induced apoptosis. We further delineate that autophagy protects from PLK1/FGFR1 inhibitor cytotoxicity and that antagonizing the compensation mechanism by clinically approved chloroquine fully realizes the therapeutic potential of PLK1 and FGFR1 targeting therapy, producing potent and durable responses in KRAS-mutant patient-derived xenografts and a genetically engineered mouse model of Kras-induced lung adenocarcinoma. These results suggest a previously unappreciated role for FGFR1 and PLK1 in the surveillance of metabolic stress and demonstrate a synergistic drug combination for treating KRAS-mutant cancer.	[Yang, Zhang; Liang, Shun-Qing; Yang, Haitang; Zhao, Liang; Gao, Yanyun; Xu, Duo; Deng, Haibin; Marti, Thomas M.; Kocher, Gregor J.; Schmid, Ralph A.; Peng, Ren-Wang] Univ Bern, Bern Univ Hosp, Inselspital, Div Gen Thorac Surg,Dept BioMed Res DBMR, Bern, Switzerland; [Yang, Zhang] Fujian Med Univ, Union Hosp, Dept Thorac Surg, Fuzhou, Peoples R China; [Saliakoura, Maria; Konstantinidou, Georgia] Univ Bern, Inst Pharmacol, Bern, Switzerland; [Vassella, Eric; Tschan, Mario] Univ Bern, Inst Pathol, Bern, Switzerland; [Hegedus, Balazs] Univ Duisburg Essen, Univ Med Essen, Ruhrlandklin, Dept Thorac Surg, Essen, Germany; [Wang, Wenxiang] Cent South Univ, Hunan Canc Hosp, Thorac Surg Dept 2, Changsha, Peoples R China; [Wang, Wenxiang] Cent South Univ, Affiliated Canc Hosp, Xiangya Sch Med, Changsha, Peoples R China		Schmid, RA; Peng, RW (corresponding author), Univ Bern, Bern Univ Hosp, Inselspital, Div Gen Thorac Surg,Dept BioMed Res DBMR, Bern, Switzerland.	ralph.schmid@insel.ch; renwang.peng@insel.ch	Hegedus, Balazs/B-6076-2008; Konstantinidou, Georgia/O-9192-2016; Yang, Haitang/M-9742-2017	Hegedus, Balazs/0000-0002-4341-4153; Konstantinidou, Georgia/0000-0001-9513-0286; Tschan, Mario P./0000-0001-5897-3647; Peng, Ren-Wang/0000-0003-1199-6520; Yang, Haitang/0000-0002-8732-5910; Yang, Zhang/0000-0001-8592-5800; Gao, Yanyun/0000-0002-1226-3073	Swiss National Science Foundation (SNSF)Swiss National Science Foundation (SNSF) [310030_192648]; Swiss Cancer League/Swiss Cancer Research Foundation [KFS-4851-08-2019]; Cancer League of the Canton of Bern; China Scholarship CouncilChina Scholarship Council	We acknowledge Matteo Rossi Sebastiano (Institute of Pharmacology, University of Bern) for animal studies and in vitro experiments. The PF139 and PF563 cell lines were established in collaboration with the West-German Biobank Essen (WBE). This work was supported by grants from Swiss National Science Foundation (SNSF; #310030_192648; to R-W. Peng), Swiss Cancer League/Swiss Cancer Research Foundation (#KFS-4851-08-2019; to R-W. Peng), Cancer League of the Canton of Bern (to R-W. Peng; G. J. Kocher.), and PhD fellowships from China Scholarship Council (to Z.Y., H.Y., Y. G., H.D.).	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Med.	SEP 7	2021	13	9							e13193	10.15252/emmm.202013193		AUG 2021	19	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	UM2IP	WOS:000682868100001	34369083	Green Published, gold			2022-04-25	
J	Roy, K; Kanwar, RK; Krishnakumar, S; Cheung, CHA; Kanwar, JR				Roy, Kislay; Kanwar, Rupinder K.; Krishnakumar, Subramanian; Cheung, Chun Hei Antonio; Kanwar, Jagat R.			Competitive inhibition of survivin using a cell-permeable recombinant protein induces cancer-specific apoptosis in colon cancer model	INTERNATIONAL JOURNAL OF NANOMEDICINE			English	Article						nanoparticle; chitosan; mucoadhesive; cytotoxicity; xenograft	CHITOSAN NANOPARTICLES; TARGETING SURVIVIN; EXPRESSION; DELIVERY; DEATH; DRUG; PROLIFERATION; DEGRADATION; ENHANCERS; RELEASE	Endogenous survivin expression has been related with cancer survival, drug resistance, and metastasis. Therapies targeting survivin have been shown to significantly inhibit tumor growth and recurrence. We found out that a cell-permeable dominant negative survivin (SurR9-C84A, referred to as SR9) competitively inhibited endogenous survivin and blocked the cell cycle at the G(1)/S phase. Nanoencapsulation in mucoadhesive chitosan nanoparticles (CHNP) substantially increased the bioavailability and serum stability of SR9. The mechanism of nanoparticle uptake was studied extensively in vitro and in ex vivo models. Our results confirmed that CHNP-SR9 protected primary cells from autophagy and successfully induced tumor-specific apoptosis via both extrinsic and intrinsic apoptotic pathways. CHNP-SR9 significantly reduced the tumor spheroid size (three-dimensional model) by nearly 7-fold. Effects of SR9 and CHNP-SR9 were studied on 35 key molecules involved in the apoptotic pathway. Highly significant (4.26-fold, P <= 0.005) reduction in tumor volume was observed using an in vivo mouse xenograft colon cancer model. It was also observed that net apoptotic (6.25-fold, P <= 0.005) and necrotic indexes (3.5-fold, P <= 0.05) were comparatively higher in CHNP-SR9 when compared to void CHNP and CHNP-SR9 internalized more in cancer stem cells (4.5-fold, P <= 0.005). We concluded that nanoformulation of SR9 did not reduce its therapeutic potential; however, nanoformulation provided SR9 with enhanced stability and better bioavailability. Our study presents a highly tumor-specific protein-based cancer therapy that has several advantages over the normally used chemotherapeutics.	[Roy, Kislay; Kanwar, Rupinder K.; Kanwar, Jagat R.] Deakin Univ, Fac Hlth, MMR Strateg Res Ctr, Sch Med,NLIMBR, Waurn Ponds, Vic 3217, Australia; [Krishnakumar, Subramanian] Vis Res Fdn, Kamalnayan Bajaj Inst Res Vis & Ophthalmol, Dept Nanobiotechnol, Madras, Tamil Nadu, India; [Krishnakumar, Subramanian] Vis Res Fdn, Kamalnayan Bajaj Inst Res Vis & Ophthalmol, L&T Ocular Pathol Dept, Madras, Tamil Nadu, India; [Cheung, Chun Hei Antonio] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70101, Taiwan		Kanwar, JR (corresponding author), Deakin Univ, Fac Hlth, MMR Strateg Res Ctr, Sch Med,NLIMBR, Waurn Ponds, Vic 3217, Australia.	jagat.kanwar@deakin.edu.au		Cheung, Chun Hei Antonio/0000-0003-4181-1435	Australia-India Strategic Research Fund (AISRF)Australian GovernmentDepartment of Industry, Innovation and Science; National Health and Medical Research Council (NHMRC)National Health and Medical Research Council (NHMRC) of Australia	The authors would like to thank the Australia-India Strategic Research Fund (AISRF) and the National Health and Medical Research Council (NHMRC) for financial support.	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J. Nanomed.		2015	10						1019	1043		10.2147/IJN.S73916			25	Nanoscience & Nanotechnology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics; Pharmacology & Pharmacy	CA2HT	WOS:000348730300002	25678789	Green Published, gold, Green Submitted			2022-04-25	
J	Cho, DH; Jo, YK; Kim, SC; Park, IJ; Kim, JC				Cho, Dong-Hyung; Jo, Yoon Kyung; Kim, Seung Cheol; Park, In Ja; Kim, Jin Cheon			Down-regulated Expression of ATG5 in Colorectal Cancer	ANTICANCER RESEARCH			English	Article						ATG5; autophagy; colorectal cancer; tumor suppressor; LVI	AUTOPHAGY; GENE; TUMORIGENESIS; DEFICIENT; ROLES	The role of autophagy in tumor development is paradoxical. Although some genetic evidence has indicated that autophagy has as a tumor suppressor function, it also provides some advantages to tumors under metabolic stress conditions. Autophagy is regulated by several autophagy-related gene (ATG) proteins. In mammals, 16 different ATG genes have been identified. To investigate the clinicopathological role of ATG5 in colorectal cancer, we firstly investigated its expression in patients with sporadic colorectal cancer. Expression analysis revealed ATG5 to be strongly down-regulated in colorectal cancer (38140 patients). Interestingly, immunohistochemical analysis of colorectal cancer tissues indicated that increased ATG5 expression is associated with lymphovascular invasion (p=0.035). The findings in our limited clinical cohort indicate that ATG5 could be a potential prognostic or diagnostic biomarker.	[Cho, Dong-Hyung; Jo, Yoon Kyung] Kyung Hee Univ, Grad Sch EW Med Sci, Yongin 446701, Gyeonggi Do, South Korea; [Jo, Yoon Kyung; Kim, Seung Cheol; Kim, Jin Cheon] Asan Med Ctr, Inst Innovat Canc Res, Seoul, South Korea; [Kim, Seung Cheol; Park, In Ja; Kim, Jin Cheon] Univ Ulsan, Coll Med, Dept Surg, Seoul, South Korea		Cho, DH (corresponding author), Kyung Hee Univ, Grad Sch EW Med Sci, 1 Seocheon Dong, Yongin 446701, Gyeonggi Do, South Korea.	dhcho@khu.ac.kr; jckim@amc.seoul.kr	Park, In Ja/U-2371-2019	Park, In Ja/0000-0001-5355-3969	Asan Institute for Life Sciences [2011-069]; Center for Development and Commercialization of Anti-Cancer Therapeutics; Korean Health 21 RD Project [A062254, A102059]; Ministry of Health, Welfare and Family Affairs, Korea), and the Basic Science Research Program [2010-0009164]; National Research Foundation, KoreaNational Research Foundation of Korea	This work was supported by the Asan Institute for Life Sciences (2011-069, Asan Foundation, Seoul, Korea), the Center for Development and Commercialization of Anti-Cancer Therapeutics and the Korean Health 21 R&D Project (A062254 and A102059, Ministry of Health, Welfare and Family Affairs, Korea), and the Basic Science Research Program (2010-0009164, the National Research Foundation, Korea).	Baylin SB, 2006, NAT REV CANCER, V6, P107, DOI 10.1038/nrc1799; Cho DH, 2010, MOL MED, V16, P271, DOI 10.2119/molmed.2009.00187; Comb WC, 2011, ONCOGENE, V30, P1727, DOI 10.1038/onc.2010.553; Degenhardt K, 2006, CANCER CELL, V10, P51, DOI 10.1016/j.ccr.2006.06.001; Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013; Hangaishi A, 2010, INT J HEMATOL, V91, P46, DOI 10.1007/s12185-009-0472-5; Homma Y, 2010, J SURG ONCOL, V102, P230, DOI 10.1002/jso.21606; Iqbal J, 2009, LEUKEMIA, V23, P1139, DOI 10.1038/leu.2009.3; Jin SK, 2007, AUTOPHAGY, V3, P28, DOI 10.4161/auto.3269; Kenific CM, 2010, CURR OPIN CELL BIOL, V22, P241, DOI 10.1016/j.ceb.2009.10.008; Kimmelman AC, 2011, GENE DEV, V25, P1999, DOI 10.1101/gad.17558811; Komatsu M, 2011, AUTOPHAGY, V7, P1088, DOI 10.4161/auto.7.9.16474; Li ZD, 2010, BMC CANCER, V10, DOI 10.1186/1471-2407-10-98; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Marino G, 2007, J BIOL CHEM, V282, P18573, DOI 10.1074/jbc.M701194200; Mizushima N, 2008, NATURE, V451, P1069, DOI 10.1038/nature06639; Morselli E, 2009, BBA-MOL CELL RES, V1793, P1524, DOI 10.1016/j.bbamcr.2009.01.006; Nagtegaal ID, 2008, J CLIN ONCOL, V26, P303, DOI 10.1200/JCO.2007.12.7027; Pasqualucci L, 2006, J EXP MED, V203, P311, DOI 10.1084/jem.20052204; Perkins ND, 2004, TRENDS CELL BIOL, V14, P64, DOI 10.1016/j.tcb.2003.12.004; Pritchard CC, 2011, GUT, V60, P116, DOI 10.1136/gut.2009.206250; Pyo JO, 2005, J BIOL CHEM, V280, P20722, DOI 10.1074/jbc.M413934200; Qu XP, 2003, J CLIN INVEST, V112, P1809, DOI 10.1172/JCI200320039; Rosenfeldt MT, 2011, CARCINOGENESIS, V32, P955, DOI 10.1093/carcin/bgr031; Semenza GL, 2010, CURR OPIN GENET DEV, V20, P51, DOI 10.1016/j.gde.2009.10.009; Takamura A, 2011, GENE DEV, V25, P795, DOI 10.1101/gad.2016211; Tilney HS, 2007, WORLD J SURG, V31, P1142, DOI 10.1007/s00268-006-0218-y; Yang ZNJ, 2011, MOL CANCER THER, V10, P1533, DOI 10.1158/1535-7163.MCT-11-0047; Yousefi S, 2006, NAT CELL BIOL, V8, P1124, DOI 10.1038/ncb1482	29	45	50	0	5	INT INST ANTICANCER RESEARCH	ATHENS	EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE	0250-7005	1791-7530		ANTICANCER RES	Anticancer Res.	SEP	2012	32	9					4091	4096					6	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	012NN	WOS:000309243200070	22993366				2022-04-25	
J	Rosati, A; Basile, A; Falco, A; d'Avenia, M; Festa, M; Graziano, V; De Laurenzi, V; Arra, C; Pascale, M; Turco, MC				Rosati, Alessandra; Basile, Anna; Falco, Antonia; d'Avenia, Morena; Festa, Michelina; Graziano, Vincenzo; De Laurenzi, Vincenzo; Arra, Claudio; Pascale, Maria; Turco, Maria Caterina			Role of BAG3 protein in leukemia cell survival and response to therapy	BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER			English	Review						BAG3; Cancer; Apoptosis; Leukemia; Autophagy	ACUTE LYMPHOBLASTIC-LEUKEMIA; COLON-CANCER CELLS; INDUCED APOPTOSIS; TUMOR-SUPPRESSOR; GENE-EXPRESSION; DILATED CARDIOMYOPATHY; BCL-2-BINDING PROTEIN; SELECTIVE AUTOPHAGY; REACTIVE ASTROCYTES; CHAPERONE ACTIVITY	The ability of BAG3, a member of the BAG family of heat shock protein (Hsp) 70 - cochaperones, to sustain the survival of human primary B-CLL and ALL cells was recognized about nine years ago. Since then, the anti-apoptotic activity of BAG3 has been confirmed in other tumor types, where it has been shown to regulate the intracellular concentration and localization of apoptosis-regulating factors, including NF-kappa B-activating (IKK gamma) and Bcl2-family (Bax) proteins. Furthermore, growing evidences support its role in lymphoid and myeloid leukemia response to therapy. Moreover in the last years, the contribution of BAG3 to autophagy, a process known to be involved in the pathogenesis and response to therapy of leukemia cells, has been disclosed, opening a new avenue for the interpretation of the role of this protein in leukemias' biology. (C) 2012 Elsevier B.V. All rights reserved.	[Pascale, Maria] Univ Salerno, Div Biomed Arturo Leone, FAMABIOMED, BIOUNIVERSA Srl, I-84084 Fisciano, SA, Italy; [Rosati, Alessandra; Basile, Anna; Falco, Antonia; d'Avenia, Morena; Festa, Michelina; Pascale, Maria; Turco, Maria Caterina] Univ Salerno, FARMABIOMED, I-84084 Fisciano, SA, Italy; [Graziano, Vincenzo; De Laurenzi, Vincenzo] Univ G dAnnunzio, Fdn G DAnnunzio, Ce SI, Dept Biomed Sci, Chieti, Italy; [Arra, Claudio] Pascale Tumor Inst, Anim Facil, Naples, Italy		Pascale, M (corresponding author), Univ Salerno, Div Biomed Arturo Leone, FAMABIOMED, BIOUNIVERSA Srl, Via Ponte Don Melillo 11-C, I-84084 Fisciano, SA, Italy.	pascale@unisa.it	TURCO, Maria Caterina/AAC-5282-2022; De Laurenzi, Vincenzo/K-7471-2016	TURCO, Maria Caterina/0000-0002-7835-359X; Rosati, Alessandra/0000-0001-6675-0857; Arra, Claudio/0000-0003-3162-2091; De Laurenzi, Vincenzo/0000-0002-7506-1743; Graziano, Vincenzo/0000-0001-7656-824X			Ammirante M, 2011, CELL DEATH DIS, V2, DOI 10.1038/cddis.2011.23; Ammirante M, 2010, P NATL ACAD SCI USA, V107, P7497, DOI 10.1073/pnas.0907696107; 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Biophys. Acta-Rev. Cancer	DEC	2012	1826	2					365	369		10.1016/j.bbcan.2012.06.001			5	Biochemistry & Molecular Biology; Biophysics; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics; Oncology	024JG	WOS:000310104900009	22710027				2022-04-25	
J	Choi, PR; Kang, YJ; Sung, B; Kim, JH; Moon, HR; Chung, HY; Kim, SE; Park, MI; Park, SJ; Kim, ND				Choi, Pyoung Rak; Kang, Yong Jung; Sung, Bokyung; Kim, Jae Hyun; Moon, Hyung Ryong; Chung, Hae Young; Kim, Sung Eun; Park, Moo In; Park, Seun Ja; Kim, Nam Deuk			MHY218-induced apoptotic cell death is enhanced by the inhibition of autophagy in AGS human gastric cancer cells	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						MHY218; gastric cancer cells; apoptosis; autophagy	HISTONE DEACETYLASE INHIBITOR; HYDROXAMIC ACID; CLASS-I; EXPRESSION PROFILE; GROWTH; COMBINATION; MODULATION; INDUCTION; PATTERNS; SURVIVAL	We previously reported the anticancer effects of MHY218, which is a hydroxamic acid derivative, in HCT116 human colon cancer cells. In the present study, the involvement of autophagy in the MHY218-induced apoptotic cell death of AGS human gastric cancer cells was investigated. MHY218 treatment induced growth inhibition and apoptotic cell death in a concentration- and time-dependent manner. The induction of apoptosis was confirmed by observations of decreased viability, DNA fragmentation, and an increase in late apoptosis and sub-G1 DNA, which were detected with a flow cytometric analysis. Western blot analyses showed that MHY218 treatment resulted in decreased protein levels of procaspase-8, -9, and -3; cleavage of poly(ADP-ribose) polymerase (PARP); and alterations in the ratio of Bax/Bcl-2 protein expression. Apoptosis induced by MHY218 was involved in the activation of caspase-8, -9, and -3, and it was blocked by the addition of Z-VAD-FMK, a pan-caspase inhibitor. In addition, autophagy-inducing effects of MHY218 were indicated by cytoplasmic vacuolation, the accumulation of acidic vesicular organelles, the appearance of green fluorescent protein-light-chain 3 (LC3) punctate dots, and increased levels of Beclin-1 and LC3-II protein expression. Pretreatment with the autophagy inhibitors LY294002, 3-methyladenine, chloroquine, and bafilomycin Al enhanced the induction of apoptosis by MHY218, and this was accompanied by an increase in PARP cleavage. Taken together, these results provide new insights into the role of MHY218 as a potential antitumor agent. The combination of MHY218 with an autophagy inhibitor might be a useful candidate for the chemoprevention and/or treatment of gastric cancer.	[Kang, Yong Jung; Sung, Bokyung; Moon, Hyung Ryong; Chung, Hae Young; Kim, Nam Deuk] Pusan Natl Univ, Coll Pharm, Mol Inflammat Res Ctr Aging Intervent MRCA, Busan 609735, South Korea; [Choi, Pyoung Rak; Kim, Jae Hyun; Kim, Sung Eun; Park, Moo In; Park, Seun Ja] Kosin Univ, Gospel Hosp, Dept Gastroenterol, Busan 602702, South Korea		Kim, ND (corresponding author), Pusan Natl Univ, Coll Pharm, Dept Pharm, Busan 609735, South Korea.	nadkim@pusan.ac.kr	Sung, Bokyung/AAX-5697-2021; Kim, Jae Hyun/AAI-9800-2020	Kim, Jae Hyun/0000-0002-4272-8003	National Research Foundation of Korea (NRF) - Korea government (MSIP) [2009-0083538]	This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (no. 2009-0083538). We thank the Aging Tissue Bank for providing research information.	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J. Oncol.	AUG	2015	47	2					563	572		10.3892/ijo.2015.3031			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CM8QC	WOS:000357965700018	26043797	Bronze			2022-04-25	
J	Zeng, XH; Kinsella, TJ				Zeng, Xuehuo; Kinsella, Timothy J.			Mammalian target of rapamycin and S6 kinase 1 positively regulate 6-thioguanine-induced autophagy	CANCER RESEARCH			English	Article							DNA MISMATCH REPAIR; DROSOPHILA FAT-BODY; HUMAN TUMOR-CELLS; MONITORING AUTOPHAGY; CANCER-CELLS; MTOR; TUMORIGENESIS; SUPPRESSOR; GROWTH; GENE	DNA mismatch repair (MMR) ensures the fidelity of DNA replication and is required for activation of cell cycle arrest and apoptosis in response to certain classes of DNA damage. We recently reported that MMR is also implicated in initiation of an autophagic response after MMR processing of 6-thioguanine (6-TG). It is now generally believed that autophagy is negatively controlled by mammalian target of rapamycin (mTOR) activity. To determine whether mTOR is involved in 6-TG-induced autophagy, we used rapamycin, a potential anticancer agent, to inhibit mTOR activity. Surprisingly, we find that rapamycin cotreatment inhibits 6-TG-induced autophagy in MMR-proficient human colorectal cancer HCT116 (MLH1(+)) and HT29 cells as measured by LC3 immunoblotting, GFP-LC3 relocalization, and acridine orange staining. Consistently, short interfering RNA silencing of the 70-kDa ribosomal S6 kinase 1 (S6K1), the downstream effector of mTOR, markedly reduces 6-TG-induced autophagy. Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. In conclusion, our data indicate that mTOR-S6K1 positively regulates autophagy after MMR processing of 6-TG probably through its negative feedback inhibition of Akt.	Case Western Reserve Univ, Univ Hosp Case Med Ctr, Dept Radiat Oncol, Cleveland, OH 44106 USA; Univ Hosp Case Med Ctr, Case Comprehens Canc Ctr, Case Integrat Canc Biol Program, Cleveland, OH 44106 USA		Kinsella, TJ (corresponding author), Case Western Reserve Univ, Univ Hosp Case Med Ctr, Dept Radiat Oncol, LTR6068,11100 Euclid Ave, Cleveland, OH 44106 USA.	timothy.kinsella@uhhospitals.org			NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA50595, R01 CA050595, CA112963, U56 CA112963] Funding Source: Medline; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA050595] Funding Source: NIH RePORTER		Arico S, 2001, J BIOL CHEM, V276, P35243, DOI 10.1074/jbc.C100319200; Corradetti MN, 2006, ONCOGENE, V25, P6347, DOI 10.1038/sj.onc.1209885; Degenhardt K, 2006, CANCER CELL, V10, P51, DOI 10.1016/j.ccr.2006.06.001; DUNN WA, 1990, J CELL BIOL, V110, P1935, DOI 10.1083/jcb.110.6.1935; Fingar DC, 2004, ONCOGENE, V23, P3151, DOI 10.1038/sj.onc.1207542; Fink D, 1998, CLIN CANCER RES, V4, P1; Gulati P, 2007, BIOCHEM SOC T, V35, P236, DOI 10.1042/BST0350236; Harrington LS, 2005, TRENDS BIOCHEM SCI, V30, P35, DOI 10.1016/j.tibs.2004.11.003; Harrington LS, 2004, J CELL BIOL, V166, P213, DOI 10.1083/jcb.200403069; Hennessy BT, 2005, NAT REV DRUG DISCOV, V4, P988, DOI 10.1038/nrd1902; Huang SL, 2003, CANCER BIOL THER, V2, P222, DOI 10.4161/cbt.2.3.360; Jacob S, 2001, CANCER RES, V61, P6555; Juhasz G, 2007, CELL DEATH DIFFER, V14, P1181, DOI 10.1038/sj.cdd.4402123; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; Kanzawa T, 2004, CELL DEATH DIFFER, V11, P448, DOI 10.1038/sj.cdd.4401359; Klionsky DJ, 2007, AUTOPHAGY, V3, P181, DOI 10.4161/auto.3678; Klionsky DJ, 2005, AUTOPHAGY, V1, P59, DOI 10.4161/auto.1.1.1536; Kuma A, 2007, AUTOPHAGY, V3, P323, DOI 10.4161/auto.4012; Manning BD, 2004, J CELL BIOL, V167, P399, DOI 10.1083/jcb.200408161; Mizushima N, 2004, INT J BIOCHEM CELL B, V36, P2491, DOI 10.1016/j.biocel.2004.02.005; Modrich P, 1996, ANNU REV BIOCHEM, V65, P101, DOI 10.1146/annurev.bi.65.070196.000533; Paglin S, 2001, CANCER RES, V61, P439; PAPADOPOULOS N, 1994, SCIENCE, V263, P1625, DOI 10.1126/science.8128251; PATTINGRE S, 2007, IN PRESS BIOCHIMIE; Petiot A, 2000, J BIOL CHEM, V275, P992, DOI 10.1074/jbc.275.2.992; Qu XP, 2003, J CLIN INVEST, V112, P1809, DOI 10.1172/JCI200320039; Rubinsztein DC, 2007, NAT REV DRUG DISCOV, V6, P304, DOI 10.1038/nrd2272; Sabatini DM, 2006, NAT REV CANCER, V6, P729, DOI 10.1038/nrc1974; Sarkar S, 2005, J CELL BIOL, V170, P1101, DOI 10.1083/jcb.200504035; Sarkar S, 2007, J BIOL CHEM, V282, P5641, DOI 10.1074/jbc.M609532200; Schmelzle T, 2000, CELL, V103, P253, DOI 10.1016/S0092-8674(00)00117-3; Scott RC, 2004, DEV CELL, V7, P167, DOI 10.1016/j.devcel.2004.07.009; SEGLEN PO, 1992, EXPERIENTIA, V48, P158, DOI 10.1007/BF01923509; SHINTANI T, 2006, CLIN CANCER RES, V12, P1961; Stocker H, 2003, NAT CELL BIOL, V5, P559, DOI 10.1038/ncb995; Stojic L, 2004, DNA REPAIR, V3, P1091, DOI 10.1016/j.dnarep.2004.06.006; Sun SY, 2005, CANCER RES, V65, P7052, DOI 10.1158/0008-5472.CAN-05-0917; Swann PF, 1996, SCIENCE, V273, P1109, DOI 10.1126/science.273.5278.1109; TRAGANOS F, 1994, METHOD CELL BIOL, V41, P185; Wang JYJ, 2006, CANCER CELL, V9, P417, DOI 10.1016/j.ccr.2006.05.013; Yan T, 2003, CLIN CANCER RES, V9, P2327; Yorimitsu T, 2005, CELL DEATH DIFFER, V12, P1542, DOI 10.1038/sj.cdd.4401765; Yue ZY, 2003, P NATL ACAD SCI USA, V100, P15077, DOI 10.1073/pnas.2436255100; ZENG X, 2007, CLIN CANCER RES, V3, P368; Zeng XH, 2007, AUTOPHAGY, V3, P368, DOI 10.4161/auto.4205; Zeng XH, 2007, CLIN CANCER RES, V13, P1315, DOI 10.1158/1078-0432.CCR-06-1517	46	90	93	0	7	AMER ASSOC CANCER RESEARCH	PHILADELPHIA	615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA	0008-5472			CANCER RES	Cancer Res.	APR 1	2008	68	7					2384	2390		10.1158/0008-5472.CAN-07-6163			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	284WU	WOS:000254738500041	18381446				2022-04-25	
J	Cheng, X; Feng, HR; Wu, HX; Jin, ZJ; Shen, XN; Kuang, J; Huo, Z; Chen, XZ; Gao, HJ; Ye, F; Ji, XP; Jing, XQ; Zhang, YQ; Zhang, T; Qiu, WH; Zhao, R				Cheng, Xi; Feng, Haoran; Wu, Haoxuan; Jin, Zhijian; Shen, Xiaonan; Kuang, Jie; Huo, Zhen; Chen, Xianze; Gao, Haoji; Ye, Feng; Ji, Xiaopin; Jing, Xiaoqian; Zhang, Yaqi; Zhang, Tao; Qiu, Weihua; Zhao, Ren			Targeting autophagy enhances apatinib-induced apoptosis via endoplasmic reticulum stress for human colorectal cancer	CANCER LETTERS			English	Article						Tyrosine kinase inhibitor; Chloroquine; IRE1 alpha; Drug resistance	RESISTANCE; PATHWAY; ER	Apatinib, a novel tyrosine kinase inhibitor (TKI), has been confirmed for its efficacy and safety in the treatment of advanced gastric carcinoma and some other solid tumors. However, the direct functional mechanisms of tumor lethality mediated by apatinib have not yet been fully characterized, and the precise mechanisms of drug resistance are largely unknown. Here, in this study, we demonstrated that apatinib could induce both apoptosis and autophagy in human colorectal cancer (CRC) via a mechanism that involved endoplasmic reticulum (ER) stress. Moreover, activation of the IRE1 alpha pathway from apatinib-induced ER stress is responsible for the induction of autophagy; however, blocking autophagy could enhance the apoptosis in apatinib-treated human CRC cell lines. Furthermore, the combination of apatinib with autophagy inhibitor chloroquine (CQ) tends to have the most significant anti-tumor effect of CRC both in vitro and in vivo. Overall, our data show that because apatinib treatment could induce ER stress-related apoptosis and protective autophagy in human CRC cell lines, targeting autophagy is a promising therapeutic strategy to relieve apatinib drug resistance in CRC.	[Cheng, Xi; Feng, Haoran; Wu, Haoxuan; Jin, Zhijian; Kuang, Jie; Huo, Zhen; Chen, Xianze; Gao, Haoji; Ye, Feng; Ji, Xiaopin; Jing, Xiaoqian; Zhang, Yaqi; Zhang, Tao; Qiu, Weihua; Zhao, Ren] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Gen Surg, Sch Med, Shanghai 200025, Peoples R China; [Cheng, Xi; Feng, Haoran; Wu, Haoxuan; Jin, Zhijian; Kuang, Jie; Huo, Zhen; Chen, Xianze; Gao, Haoji; Ye, Feng; Ji, Xiaopin; Jing, Xiaoqian; Zhang, Yaqi; Zhang, Tao; Qiu, Weihua; Zhao, Ren] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Digest Surg, Sch Med, Shanghai 200025, Peoples R China; [Cheng, Xi; Zhao, Ren] Shanghai Jiao Tong Univ, Ruijin North Hosp, Dept Gen Surg, Sch Med, Shanghai 201801, Peoples R China; [Shen, Xiaonan] Shanghai Jiao Tong Univ, Renji Hosp, Dept Gastroenterol, Sch Med, Shanghai 200001, Peoples R China		Zhang, T; Qiu, WH; Zhao, R (corresponding author), Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Gen Surg, Sch Med, Shanghai 200025, Peoples R China.	woodyhom@yahoo.com; qwh11072@rjh.com.cn; rjzhaoren@139.com			Nature Science Foundation of China NSFCNational Natural Science Foundation of China (NSFC) [81772558]; Clinical Skill and Innovation 3-year program of Shanghai Hospital Development Center [16CR2064B]; Ph.D. Innovation Fund of Shanghai Jiaotong University School of Medicine [BXJ201709]	Nature Science Foundation of China NSFC (81772558), Clinical Skill and Innovation 3-year program of Shanghai Hospital Development Center (16CR2064B), Ph.D. Innovation Fund of Shanghai Jiaotong University School of Medicine (BXJ201709) and "Visiting Programs for Graduate Students of Shanghai Jiaotong University School of Medicine".	Ansari SS, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0342-2; Bakhtou H., 2018, CURR DRUG DISCOV TEC; Bel S, 2018, AUTOPHAGY, V14, P719, DOI 10.1080/15548627.2018.1430462; Besio R, 2018, BBA-MOL BASIS DIS, V1864, P1642, DOI 10.1016/j.bbadis.2018.02.002; Bhattacharjee A, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-20541-8; Cespedes Feliciano EM, 2016, J CLIN ONCOL, V34, P3664, DOI 10.1200/JCO.2016.67.4473; Cheng X, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-10267-4; Cheng X, 2016, ONCOTARGET, V7, P77916, DOI 10.18632/oncotarget.12844; Daniels MS, 2017, J CLIN ONCOL, V35, P2588, DOI 10.1200/JCO.2017.72.7222; Das CK, 2018, NEOPLASIA, V20, P263, DOI 10.1016/j.neo.2018.01.001; Fang ZJ, 2018, CANCER LETT, V415, P58, DOI 10.1016/j.canlet.2017.11.040; Fu ZP, 2018, MOL ONCOL, V12, P529, DOI 10.1002/1878-0261.12179; Gao YN, 2017, CELL PHYSIOL BIOCHEM, V43, P1503, DOI 10.1159/000481974; Jang JE, 2017, AUTOPHAGY, V13, P761, DOI 10.1080/15548627.2016.1278328; Jin ZJ, 2017, CELL PHYSIOL BIOCHEM, V44, P1471, DOI 10.1159/000485583; Khaket TP, 2018, CELL SIGNAL, V46, P92, DOI 10.1016/j.cellsig.2018.02.017; Li F, 2017, EUR J CANCER, V84, P184, DOI 10.1016/j.ejca.2017.07.037; Li J, 2013, J CLIN ONCOL, V31, P3219, DOI 10.1200/JCO.2013.48.8585; Li K, 2016, CANCER RES, V76, P4205, DOI 10.1158/0008-5472.CAN-15-3385; Li WM, 2017, NAT COMMUN, V8, DOI 10.1038/s41467-017-01609-x; Liu KS, 2017, CELL DEATH DIS, V8, DOI 10.1038/cddis.2017.422; Lu X, 2017, GENE DEV, V31, P2337, DOI 10.1101/gad.307116.117; Mishra RR, 2018, CLIN CANCER RES, V24, P1987, DOI 10.1158/1078-0432.CCR-17-2776; Ou BC, 2016, CANCER LETT, V380, P457, DOI 10.1016/j.canlet.2016.07.004; Peng S, 2016, CANCER LETT, V373, P193, DOI 10.1016/j.canlet.2016.01.015; Punt CJA, 2017, NAT REV CLIN ONCOL, V14, P235, DOI 10.1038/nrclinonc.2016.171; Renfro LA, 2016, J CLIN ONCOL, V34, P144, DOI 10.1200/JCO.2015.61.6441; Sepulveda AR, 2017, J CLIN ONCOL, V35, P1453, DOI 10.1200/JCO.2016.71.9807; Smeby J, 2018, ANN ONCOL, V29, P1227, DOI 10.1093/annonc/mdy085; Tauriello DVF, 2017, MOL ONCOL, V11, P97, DOI 10.1002/1878-0261.12018; Wu L, 2017, IRAN J BASIC MED SCI, V20, P990, DOI 10.22038/IJBMS.2017.9263; Yeung B, 2018, MOL CANCER RES, V16, P1035, DOI 10.1158/1541-7786.MCR-17-0684; Zhang Y, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-13192-8; Zheng WL, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-21567-8	34	63	67	1	18	ELSEVIER IRELAND LTD	CLARE	ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND	0304-3835	1872-7980		CANCER LETT	Cancer Lett.		2018	431						105	114		10.1016/j.canlet.2018.05.046			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GM8KM	WOS:000438477500011	29859300	hybrid			2022-04-25	
J	Aredia, F; Czaplinski, S; Fulda, S; Scovassi, AI				Aredia, Francesca; Czaplinski, Sebastian; Fulda, Simone; Scovassi, A. Ivana			Molecular features of the cytotoxicity of an NHE inhibitor: Evidence of mitochondrial alterations, ROS overproduction and DNA damage	BMC CANCER			English	Article						Apoptosis; Autophagy; HMA; Mitochondria; NHE; PAR; RIPK3; ROS	CELL-DEATH; CANCER; NECROPTOSIS; APOPTOSIS; STRESS; POLY(ADP-RIBOSE); MECHANISMS; AMILORIDE; WARBURG; PATHWAY	Background: NH exchangers (NHEs) play a crucial role in regulating intra/extracellular pH, which is altered in cancer cells, and are therefore suitable targets to alter cancer cell metabolism in order to inhibit cell survival and proliferation. Among NHE inhibitors, amiloride family members are commonly used in clinical practice as diuretics; we focused on the amiloride HMA, reporting a net cytotoxic effect on a panel of human cancer cell lines; now we aim to provide new insights into the molecular events leading to cell death by HMA. Methods: Colon cancer cell lines were treated with HMA and analysed with: morphological and cellular assays for cell viability and death, and autophagy; biochemical approaches to evaluate mitochondrial function and ROS production; in situ detection of DNA damage; molecular tools to silence crucial autophagy/necroptosis factors. Results: HMA affects cellular morphology, alters mitochondrial structure and function, causes an increase in ROS, which is detrimental to DNA integrity, stimulates poly(ADP-ribose) synthesis, activates RIPK3-dependent death and triggers autophagy, which is unable to rescue cell survival. These features are hot points of an intricate network of processes, including necroptosis and autophagy, regulating the homeostasis between survival and death. Conclusion: Our results allow the identification of multiple events leading to cell death in cancer cells treated with HMA. The here-defined intricate network activated by HMA could be instrumental to selectively target the key players of each pathway in the attempt to improve the global response to HMA. Our data could be the starting point for developing a newly designed targeted therapy.	[Aredia, Francesca; Scovassi, A. Ivana] CNR, Ist Genet Mol, Via Abbiategrasso 207, I-27100 Pavia, Italy; [Aredia, Francesca] Univ Pavia, Dipartimento Biol & Biotecnol L Spallanzani, Via Ferrata 9, I-27100 Pavia, Italy; [Czaplinski, Sebastian; Fulda, Simone] Goethe Univ, Inst Expt Canc Res Pediat, Komturstr 3A, D-60528 Frankfurt, Germany		Scovassi, AI (corresponding author), CNR, Ist Genet Mol, Via Abbiategrasso 207, I-27100 Pavia, Italy.	scovassi@igm.cnr.it		Fulda, Simone/0000-0002-0459-6417			Aguilera-Aguirre L, 2014, J IMMUNOL, V193, P4643, DOI 10.4049/jimmunol.1401625; Ahmad T, 2013, CELL DEATH DIS, V4, DOI 10.1038/cddis.2012.213; Altairac S, 2003, CELL DEATH DIFFER, V10, P548, DOI 10.1038/sj.cdd.4401195; Aredia F., 2014, CANC CELL MICROENV, V1, P72; Aredia F, 2014, BIOCHEM PHARMACOL, V92, P157, DOI 10.1016/j.bcp.2014.06.021; Aredia F, 2013, APOPTOSIS, V18, P1586, DOI 10.1007/s10495-013-0898-3; Basello DA, 2015, MITOCHONDRION, V24, P56, DOI 10.1016/j.mito.2015.07.005; BRIAND J-P, 1989, Peptide Research, V2, P381; Campalans A, 2013, NUCLEIC ACIDS RES, V41, P3115, DOI 10.1093/nar/gkt025; Croce AC, 2004, BIOCHEM PHARMACOL, V67, P1035, DOI 10.1016/j.bcp.2003.10.034; Fatokun AA, 2014, BRIT J PHARMACOL, V171, P2000, DOI 10.1111/bph.12416; Acevedo-Olvera LF, 2015, CYTOKINE, V75, P142, DOI 10.1016/j.cyto.2015.06.020; Fernandez-Capetillo O, 2002, NAT CELL BIOL, V4, P993, DOI 10.1038/ncb884; Fulda S, 2013, CANCER BIOL THER, V14, P999, DOI 10.4161/cbt.26428; Galluzzi L, 2008, CELL, V135, P1161, DOI 10.1016/j.cell.2008.12.004; Giansanti V, 2012, EUR J HISTOCHEM, V56, P16, DOI 10.4081/ejh.2012.e3; Giansanti V, 2013, J CELL MOL MED, V17, P103, DOI 10.1111/j.1582-4934.2012.01652.x; Grecchi S, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0044935; Ortiz LMG, 2014, BIOMED RES INT, V2014, DOI 10.1155/2014/924585; Harguindey S, 2013, J TRANSL MED, V11, DOI 10.1186/1479-5876-11-282; Hariri M, 2000, MOL BIOL CELL, V11, P255, DOI 10.1091/mbc.11.1.255; HAWN MT, 1995, CANCER RES, V55, P3721; Holmstrom KM, 2014, NAT REV MOL CELL BIO, V15, P411, DOI 10.1038/nrm3801; Khamphio M, 2016, LIFE SCI, V158, P46, DOI 10.1016/j.lfs.2016.06.017; Kimura K, 2016, J CARDIOL, V67, P307, DOI 10.1016/j.jjcc.2015.07.017; Kroemer G, 2014, SEMIN CELL DEV BIOL, V35, P1, DOI 10.1016/j.semcdb.2014.08.005; Lalaoui N, 2015, SEMIN CELL DEV BIOL, V39, P63, DOI 10.1016/j.semcdb.2015.02.003; Leon LJ, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0063038; Liberti MV, 2016, TRENDS BIOCHEM SCI, V41, P211, DOI 10.1016/j.tibs.2015.12.001; Malatesta M, 2012, Eur J Histochem, V56, pe20, DOI 10.4081/ejh.2012.20; Matthews H, 2011, INT J CANCER, V129, P2051, DOI 10.1002/ijc.26156; Moriwaki K, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2015.16; Murai M, 2015, BIOCHEMISTRY-US, V54, P2739, DOI 10.1021/acs.biochem.5b00187; Nagelkerke A, 2014, BBA-REV CANCER, V1846, P277, DOI 10.1016/j.bbcan.2014.07.006; Nikitaki Z, 2015, FRONT CHEM, V3, DOI 10.3389/fchem.2015.00035; Otto AM, 2016, CANCER METAB, V4, DOI 10.1186/s40170-016-0145-9; Pasupuleti N, 2015, MOL PHARMACOL, V87, P683, DOI 10.1124/mol.114.096602; Pasupuleti N, 2013, J PHARMACOL EXP THER, V344, P600, DOI 10.1124/jpet.112.200519; Rowson-Hodel AR, 2016, CANCER LETT, V375, P62, DOI 10.1016/j.canlet.2016.02.042; SANDELL JH, 1988, J HISTOCHEM CYTOCHEM, V36, P555, DOI 10.1177/36.5.3356898; Shimizu S, 2014, INT J MOL SCI, V15, P3145, DOI 10.3390/ijms15023145; Spill F, 2016, CURR OPIN BIOTECH, V40, P41, DOI 10.1016/j.copbio.2016.02.007; Spugnini EP, 2015, BBA-BIOMEMBRANES, V1848, P2715, DOI 10.1016/j.bbamem.2014.10.015; Virag L, 2013, MOL ASPECTS MED, V34, P1153, DOI 10.1016/j.mam.2013.01.007; Wang H, 1999, FREE RADICAL BIO MED, V27, P612, DOI 10.1016/S0891-5849(99)00107-0; Wang L, 2013, LIFE SCI, V93, P344, DOI 10.1016/j.lfs.2013.07.007; Wang YQ, 2012, AUTOPHAGY, V8, P1462, DOI 10.4161/auto.21211; Yang Y, 2016, ONCOL REP, V35, P1255, DOI 10.3892/or.2015.4484; Zhao YQ, 2016, APOPTOSIS, V21, P517, DOI 10.1007/s10495-016-1236-3	49	9	10	0	4	BMC	LONDON	CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND	1471-2407			BMC CANCER	BMC Cancer	NOV 5	2016	16								851	10.1186/s12885-016-2878-9			14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EB8KL	WOS:000387639800001	27816051	Green Published, gold			2022-04-25	
J	Gong, K; Chen, C; Zhan, Y; Chen, Y; Huang, ZB; Li, WH				Gong, Ke; Chen, Chao; Zhan, Yao; Chen, Yan; Huang, Zebo; Li, Wenhua			Autophagy-related Gene 7 (ATG7) and Reactive Oxygen Species/Extracellular Signal-regulated Kinase Regulate Tetrandrine-induced Autophagy in Human Hepatocellular Carcinoma	JOURNAL OF BIOLOGICAL CHEMISTRY			English	Article							COLON-CANCER CELLS; CYTOCHROME-C; APOPTOSIS; DEATH; ACTIVATION; PATHWAY; MITOCHONDRIA; THERAPY; GROWTH; PERMEABILIZATION	Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the broadly used Chinese medicinal herb Stephaniae tetrandrae, exhibits potent antitumor effects and has the potential to be used as a cancer chemotherapeutic agent. We previously reported that high concentrations of tetrandrine induce apoptosis in liver cancer cells. Here, we found that in human hepatocellular carcinoma (HCC) cells, a low dose of tetrandrine (5 mu M) induced the expression of LC3-II, resulted in the formation of acidic autophagolysosome vacuoles (AVOs), and caused a punctate fluorescence pattern with the GFP-LC3 protein, which all are markers for cellular autophagy. Tetrandrine induced the production of intracellular reactive oxygen species (ROS), and treatment with ROS scavengers significantly abrogated the tetrandrine-induced autophagy. These results suggest that the generation of ROS plays an important role in promoting tetrandrine-induced autophagy. Tetrandrine-induced mitochondrial dysfunction resulted in ROS accumulation and autophagy. ROS generation activated the ERK MAP kinase, and the ERK signaling pathway at least partially contributed to tetrandrine-induced autophagy in HCC cells. Moreover, we found that tetrandrine transcriptionally regulated the expression of autophagy related gene 7 (ATG7), which promoted tetrandrine-induced autophagy. In addition to in vitro studies, similar results were also observed in vivo, where tetrandrine caused the accumulation of ROS and induced cell autophagy in a tumor xenograft model. Interestingly, tetrandrine treatment also induced autophagy in a ROS-dependent manner in C. elegans muscle cells. Therefore, these findings suggest that tetrandrine is a potent autophagy agonist and may be a promising clinical chemotherapeutic agent.	[Gong, Ke; Chen, Chao; Zhan, Yao; Li, Wenhua] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China; [Chen, Yan; Huang, Zebo] Wuhan Univ, Coll Pharm, Wuhan 430071, Peoples R China		Li, WH (corresponding author), Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China.	whli@whu.edu.cn	Huang, Zebo/AAF-2382-2019	Huang, Zebo/0000-0003-2431-3741	National Basic Research Program of ChinaNational Basic Research Program of China [2010CB529800]; National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81273540]; Chinese 111 projectMinistry of Education, China - 111 Project [B06018]; major scientific and technological special project for "Significant Creation of New Drugs" [2011ZX09102-001-32, 2011ZX09401-302-4]	This work was supported by National Basic Research Program of China Grant 2010CB529800, National Nature Science Foundation of China Grant 81273540, The Chinese 111 project (B06018), and the major scientific and technological special project for "Significant Creation of New Drugs" Grants 2011ZX09102-001-32 and 2011ZX09401-302-4.	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Biol. Chem.	OCT 12	2012	287	42					35576	35588		10.1074/jbc.M112.370585			13	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	022OF	WOS:000309968000070	22927446	Green Published, hybrid			2022-04-25	
J	Yuan, DP; Zhu, YN				Yuan, Danping; Zhu, Yanan			Knockdown of LINC01224 Suppresses Colon Cancer Progression by Sponging miR-485-5p to Downregulate MCL1	CANCER MANAGEMENT AND RESEARCH			English	Article						colon cancer; LINC01224; miR-485-5p; MCL1	LONG NONCODING RNAS; CLASSIFICATION; AUTOPHAGY; BCL2	Background: Colon cancer (CC) is the most commonly occurring malignant tumor in the world. The current cancer treatment options have been less effective especially in the advanced stages of CC and patients have poor overall survival. Hence, there is an urgent need to explore novel molecular therapeutic targets for CC treatment. Methods: qRT-PCR was performed to detect the levels of lncRNA LINC01224 (LINC01224), microRNA-485-5p (miR-485-5p), MCL1 in CC tumor tissues or cell lines. Two si-RNAs against LINC01224 were used to silence the level of LINC01224, and CCK-8 assay, colony formation assay, and transwell assay were performed to explore the role of LINC01224 on the proliferation, migration, and invasion of CC cell lines. Kaplan-Meier method was applied for evaluating the association between LINC01224 level and the overall survival of CC patients. Through bioinformatics analysis, we found that LINC01224 sponged miR-485-5p and consequently targeted MCL1. Dual-luciferase reporter assay, RNA pull down assay, qRT-PCR, and Western blot assay were conducted for verification of the interactions among LINC01224, miR-485-5p, and MCL1. Furthermore, the role of LINC01224/miR-485-5p/MCL1 axis in CC progression was investigated by CCK-8 assay, colony formation assay, and transwell assay. Results: LINC01224 was highly expressed in CC tumor tissues and CC cell lines, and its expression was associated with the overall survival of CC patients. The LINC01224-siRNAs (si-LINC01224) markedly suppressed the level of LINC01224 in CC cell lines (HT29 and SW480 cells) and consequently significantly suppressed the proliferation, migration, and invasion of the HT29 and SW480 cells. LINC01224 was verified to sponge miR-485-5p and consequently targeted MCL1. MiR-485-5p inhibitor or MCL1 overexpression (MCL1 OE) markedly restored the repressive effect of the si-LINC01224 pool on MCL1 expression level, as well as proliferation, migration, and invasion of HT29 and SW480 cells. Conclusion: This study identified LINC01224/miR-485-5p/MCL1 axis as a novel molecular therapeutic target involved in CC progression.	[Yuan, Danping] Ningbo First Hosp, Dept Colorectal Surg, Ningbo 315010, Zhejiang, Peoples R China; [Zhu, Yanan] Taizhou Hosp Zhejiang Prov, Dept Emergency, 150 Ximen St, Linhai 317000, Zhejiang, Peoples R China		Zhu, YN (corresponding author), Taizhou Hosp Zhejiang Prov, Dept Emergency, 150 Ximen St, Linhai 317000, Zhejiang, Peoples R China.	zya_cs@163.com					Burki TK, 2017, LANCET ONCOL, V18, pE437, DOI 10.1016/S1470-2045(17)30502-8; Campbell KJ, 2018, OPEN BIOL, V8, DOI 10.1098/rsob.180002; Gong JN, 2016, BLOOD, V128, P1834, DOI 10.1182/blood-2016-03-704908; Hong WW, 2020, MOL THER-NUCL ACIDS, V19, P1209, DOI 10.1016/j.omtn.2019.12.006; Hu XX, 2018, J CANCER, V9, P2603, DOI 10.7150/jca.24918; Jarroux J, 2017, ADV EXP MED BIOL, V1008, P1, DOI 10.1007/978-981-10-5203-3_1; Kawakami H, 2015, J GASTROINTEST ONCOL, V6, P676, DOI 10.3978/j.issn.2078-6891.2015.065; Kim YJ, 2015, BIOORG MED CHEM LETT, V25, P2559, DOI 10.1016/j.bmcl.2015.04.054; Li GJ, 2019, BIOL RES, V52, DOI 10.1186/s40659-019-0269-9; Li JB, 2018, ONCOL REP, V40, P554, DOI 10.3892/or.2018.6449; Lou C, 2016, CELL DEATH DIS, V7, DOI 10.1038/cddis.2016.27; Lu YP, 2019, NANOSCALE RES LETT, V14, DOI 10.1186/s11671-019-2985-z; Na HY, 2020, MOL THER-NUCL ACIDS, V21, P480, DOI 10.1016/j.omtn.2020.06.011; Peng YC, 2019, BIOMED PHARMACOTHER, V116, DOI 10.1016/j.biopha.2019.109027; Qu XL, 2014, GENOMICS, V104, P242, DOI 10.1016/j.ygeno.2013.11.002; Schaukowitch K, 2014, NEUROSCIENCE, V264, P25, DOI 10.1016/j.neuroscience.2013.12.009; Shi XF, 2013, CANCER LETT, V339, P159, DOI 10.1016/j.canlet.2013.06.013; Siegel RL, 2017, CA-CANCER J CLIN, V67, P7, DOI 10.3322/caac.21387; Sun T, 2018, PHARMACOL RES, V129, P151, DOI 10.1016/j.phrs.2017.11.009; Tong ZG, 2015, BIOMED PHARMACOTHER, V75, P129, DOI 10.1016/j.biopha.2015.07.036; Tu AF, 2019, BIOMED PHARMACOTHER, V118, DOI 10.1016/j.biopha.2019.109213; Wender RC, 2019, CA-CANCER J CLIN, V69, P50, DOI 10.3322/caac.21550; Wu YL, 2018, J BIOCHEM MOL TOXIC, V32, DOI 10.1002/jbt.22008; Xing SJ, 2020, ONCOTARGETS THER, V13, P5643, DOI 10.2147/OTT.S254662; Yan XH, 2015, CANCER CELL, V28, P529, DOI 10.1016/j.ccell.2015.09.006; Zhou BH, 2018, BIOMED PHARMACOTHER, V106, P850, DOI 10.1016/j.biopha.2018.07.003; Zhuang ST, 2020, MOL GENET GENOM MED, V8, DOI 10.1002/mgg3.1125	27	0	0	0	0	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1179-1322			CANCER MANAG RES	Cancer Manag. Res.		2021	13						7803	7812		10.2147/CMAR.S289024			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	WH1VT	WOS:000707475300002	34675675	Green Published, gold			2022-04-25	
J	Raposo, LR; Silva, A; Silva, D; Roma-Rodrigues, C; Espadinha, M; Baptista, PV; Santos, MMM; Fernandes, AR				Raposo, Luis R.; Silva, Ana; Silva, Dario; Roma-Rodrigues, Catarina; Espadinha, Margarida; Baptista, Pedro, V; Santos, Maria M. M.; Fernandes, Alexandra R.			Exploiting the antiproliferative potential of spiropyrazoline oxindoles in a human ovarian cancer cell line	BIOORGANIC & MEDICINAL CHEMISTRY			English	Article						Chemotherapy; Compound-DNA interaction; Cytotoxicity; Ovarian cancer; Spiropyrazoline oxindoles	SPIROOXINDOLE; DNA; MITOCHONDRIA	Cancer is still one of the deadliest diseases worldwide despite the efforts in its early detection and treatment strategies. However, most chemotherapeutic agents still present side effects in normal tissues and acquired resistance that limit their efficacy. Spiropyrazoline oxindoles might be good alternatives as they have shown antiproliferative activity in human breast and colon cancer cell lines, without eliciting cytotoxicity in healthy cells. However, their potential for ovarian cancer was never tested. In this work, the antiproliferative activity of five spiropyrazoline oxindoles was assessed in ovarian cancer cells A2780 and the biological targets and mechanism of action of the most promising compound evaluated. Compound la showed the highest antiproliferative effect, as well as the highest selectivity for A2780 cells compared to healthy fibroblasts. This antiproliferative effect results from the induction of cell death by mitochondria-mediated apoptosis and autophagy. In vitro DNA interaction studies demonstrated that la interacts with DNA by groove-binding, without triggering genotoxicity. In addition, la showed a strong affinity to bovine serum albumin that might be important for further inclusion in drug delivery platforms. Proteomic studies reinforced la role in promoting A2780 endoplasmatic reticulum (ER) stress by destabilizing the correct protein folding which triggers cell death via apoptosis and autophagy.	[Raposo, Luis R.; Silva, Ana; Roma-Rodrigues, Catarina; Baptista, Pedro, V; Fernandes, Alexandra R.] Univ Nova Lisboa, Dept Ciencias Vida, UCIBIO, Fac Ciencias & Tecnol, Campus Caparica, P-2829516 Caparica, Portugal; [Silva, Dario; Espadinha, Margarida; Santos, Maria M. M.] Univ Lisbon, Fac Pharm, Res Inst Med iMedULisboa, Ave Prof Gama Pinto, P-1649003 Lisbon, Portugal		Fernandes, AR (corresponding author), Univ Nova Lisboa, Dept Ciencias Vida, UCIBIO, Fac Ciencias & Tecnol, Campus Caparica, P-2829516 Caparica, Portugal.; Santos, MMM (corresponding author), Univ Lisbon, Fac Pharm, Res Inst Med iMedULisboa, Ave Prof Gama Pinto, P-1649003 Lisbon, Portugal.	mariasantos@ff.ulisboa.pt; ma.fernandes@fct.unl.pt	Raposo, Luís R/T-3754-2017; Espadinha, Margarida/AAW-9881-2021; Roma-Rodrigues, Catarina/AAT-5658-2021; Roma-Rodrigues, Catarina/S-6144-2016; Raposo, Luís/AAX-1610-2021; Baptista, Pedro/A-1237-2009; Fernandes, Alexandra/C-7465-2011; Santos, Maria/I-7189-2013	Raposo, Luís R/0000-0002-8637-346X; Roma-Rodrigues, Catarina/0000-0002-8676-6562; Roma-Rodrigues, Catarina/0000-0002-8676-6562; Raposo, Luís/0000-0002-8637-346X; Baptista, Pedro/0000-0001-5255-7095; Fernandes, Alexandra/0000-0003-2054-4438; Santos, Maria/0000-0002-2239-9353; Silva, Dario/0000-0002-2565-089X	FCTPortuguese Foundation for Science and TechnologyEuropean Commission [UIDB/04378/2020, UIDB/04138/2020, PTDC/QUI-QOR/29664/2017, CEECIND/01772/2017, SFRH/BPD/124612/2016, SFRH/BD/117931/2016, PTDC/NAN-MAT/31100/2017]	We thank A. Carvalho for preliminary data management. This work was financed by national funds from FCT through the Applied Molecular Biosciences Unit - UCIBIO (UIDB/04378/2020), iMed.ULisboa (UIDB/04138/2020), project PTDC/QUI-QOR/29664/2017, Principal Researcher grant CEECIND/01772/2017 (M. M. M. Santos), and fellowships SFRH/BPD/124612/2016 (C. Roma-Rodrigues), SFRH/BD/117931/2016 (M. Espadinha) and PTDC/NAN-MAT/31100/2017 (L.R. Raposo).	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Med. Chem.	JAN 15	2021	30								115880	10.1016/j.bmc.2020.115880			11	Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry	QE2NF	WOS:000616047600007	33348171				2022-04-25	
J	Ambrose, AJ; Zerio, CJ; Sivinski, J; Schmidlin, CJ; Shi, TD; Ross, AB; Widrick, KJ; Johnson, SM; Zhang, DD; Chapman, E				Ambrose, Andrew J.; Zerio, Christopher J.; Sivinski, Jared; Schmidlin, Cody J.; Shi, Taoda; Ross, Alison B.; Widrick, Kimberly J.; Johnson, Steven M.; Zhang, Donna D.; Chapman, Eli			A high throughput substrate binding assay reveals hexachlorophene as an inhibitor of the ER-resident HSP70 chaperone GRP78	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS			English	Article						Chaperone; HSP70; GRP78/BiP; Cancer; ER stress; UPR; ERAD; Autophagy	HEAT-SHOCK-PROTEIN-70 FAMILY; PROTEINS	Glucose-regulated protein 78 (GRP78) is the ER resident 70 kDa heat shock protein 70 (HSP70) and has been hypothesized to be a therapeutic target for various forms of cancer due to its role in mitigating proteotoxic stress in the ER, its elevated expression in some cancers, and the correlation between high levels for GRP78 and a poor prognosis. Herein we report the development and use of a high throughput fluorescence polarization-based peptide binding assay as an initial step toward the discovery and development of GRP78 inhibitors. This assay was used in a pilot screen to discover the anti-infective agent, hexachlorophene, as an inhibitor of GRP78. Through biochemical characterization we show that hexachlorophene is a competitive inhibitor of the GRP78-peptide interaction. Biological investigations showed that this molecule induces the unfolded protein response, induces autophagy, and leads to apoptosis in a colon carcinoma cell model, which is known to be sensitive to GRP78 inhibition.	[Ambrose, Andrew J.; Zerio, Christopher J.; Sivinski, Jared; Schmidlin, Cody J.; Shi, Taoda; Ross, Alison B.; Widrick, Kimberly J.; Zhang, Donna D.; Chapman, Eli] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, 1703 East Mabel St,POB 210207, Tucson, AZ 85721 USA; [Johnson, Steven M.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, 635 Barnhill Dr, Indianapolis, IN 46202 USA		Chapman, E (corresponding author), Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, 1703 East Mabel St,POB 210207, Tucson, AZ 85721 USA.	chapman@pharmacy.arizona.edu	Ambrose, Andrew/AAP-3641-2021	Ambrose, Andrew/0000-0002-2932-4514; Ross, Alison/0000-0003-1047-3031; Sivinski, Jared/0000-0003-2696-6279; Chapman, Eli/0000-0002-6310-1664; Zerio, Christopher/0000-0003-4053-4835	National Institutes of Health T32 Training GrantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [GM008804]; National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM120350]; NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [P30ES006694] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM120350, T32GM008804] Funding Source: NIH RePORTER	This work was supported by funding from the National Institutes of Health T32 Training Grant GM008804 and National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) under Award Number R01GM120350.	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Med. Chem. Lett.	JUL 15	2019	29	14					1689	1693		10.1016/j.bmcl.2019.05.041			5	Chemistry, Medicinal; Chemistry, Organic	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy; Chemistry	IA8CP	WOS:000469785600001	31129054	Green Accepted, Bronze, Green Submitted			2022-04-25	
J	Chaurasia, M; Bhatt, AN; Das, A; Dwarakanath, BS; Sharma, K				Chaurasia, Madhuri; Bhatt, Anant Narayan; Das, Asmita; Dwarakanath, Bilikere S.; Sharma, Kulbhushan			Radiation-induced autophagy: mechanisms and consequences	FREE RADICAL RESEARCH			English	Review						Calcium; DNA damage response; ER stress; mitophagy; oxidative stress	ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; PHOSPHATIDYLINOSITOL 3-KINASE COMPLEXES; COLON-CANCER CELLS; DNA-DAMAGE; ER STRESS; IONIZING-RADIATION; INDUCED APOPTOSIS; REACTIVE OXYGEN; OXIDATIVE STRESS	Autophagy is an evolutionary conserved, indispensable, lysosome-mediated degradation process, which helps in maintaining homeostasis during various cellular traumas. During stress, a context-dependent role of autophagy has been observed which drives the cell towards survival or death depending upon the type, time, and extent of the damage. The process of autophagy is stimulated during various cellular insults, e.g. oxidative stress, endoplasmic reticulum stress, imbalances in calcium homeostasis, and altered mitochondrial potential. Ionizing radiation causes ROS-dependent as well as ROS-independent damage in cells that involve macromolecular (mainly DNA) damage, as well as ER stress induction, both capable of inducing autophagy. This review summarizes the current understanding on the roles of oxidative stress, ER stress, DNA damage, altered mitochondrial potential, and calcium imbalance in radiation-induced autophagy as well as the merits and limitations of targeting autophagy as an approach for radioprotection and radiosensitization.	[Chaurasia, Madhuri; Bhatt, Anant Narayan; Dwarakanath, Bilikere S.; Sharma, Kulbhushan] Inst Nucl Med & Allied Sci, Div Metab Cell Signaling Res, Brig SK Mazumdar Marg, Delhi 110054, India; [Chaurasia, Madhuri; Das, Asmita] Delhi Technol Univ, Dept Biotechnol, Delhi, India; [Dwarakanath, Bilikere S.] Sri Ramachandra Univ, Cent Res Facil, Madras, Tamil Nadu, India		Dwarakanath, BS; Sharma, K (corresponding author), Inst Nucl Med & Allied Sci, Div Metab Cell Signaling Res, Brig SK Mazumdar Marg, Delhi 110054, India.	dwarakanathdrbs@gmail.com; kulsinmas@gmail.com	SHARMA, KULBHUSHAN/AAD-7713-2019	SHARMA, KULBHUSHAN/0000-0001-5226-4209; Dwarakanath, Bilikere S./0000-0001-6988-2601; Das, Asmita/0000-0001-9846-1005	DRDO, Govt. of IndiaDefence Research & Development Organisation (DRDO) [INM-311]; ICMR, Govt. of IndiaIndian Council of Medical Research (ICMR)	The authors report that they have no conflicts of interest. The authors alone are responsible for the content and writing of the paper. Work in author's laboratories is supported by grants from DRDO, Govt. of India (INM-311). Ms Madhuri Chaurasia is a recipient of fellowship from ICMR, Govt. of India.	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Zois CE, 2009, AUTOPHAGY, V5, P442, DOI 10.4161/auto.5.4.7667	179	50	52	3	50	TAYLOR & FRANCIS LTD	ABINGDON	2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND	1071-5762	1029-2470		FREE RADICAL RES	Free Radic. Res.	MAR 3	2016	50	3					273	290		10.3109/10715762.2015.1129534			18	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	DB6GD	WOS:000368611500001	26764568				2022-04-25	
J	Liu, F; Ai, FY; Zhang, DC; Tian, L; Yang, ZY; Liu, SJ				Liu, Fen; Ai, Fei-Yan; Zhang, De-Cai; Tian, Li; Yang, Zhen-Yun; Liu, Shao-Jun			LncRNA NEAT1 knockdown attenuates autophagy to elevate 5-FU sensitivity in colorectal cancer via targeting miR-34a	CANCER MEDICINE			English	Article						autophagy; colorectal carcinoma; HMGB1; LncRNA NEAT1; miR-34a	CELL-PROLIFERATION; PROMOTES; CHEMORESISTANCE; OSTEOSARCOMA; SURVIVAL; INVASION; GROWTH; HMGB1; AXIS	Backgrounds Colorectal carcinoma (CRC) is a common malignant tumor. Increasing evidences indicated that CRC showed a resistance to 5-fluorouracil (5-FU) and further resulted in a poor prognosis. In this study, we aim to investigate the effect of long noncoding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) on cell viability, sensitivity to 5-FU, and autophagy of CRC cell lines. Methods MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-Htetrazolium bromide) was used to detect cell viability, immunofluorescent staining was used to detect autophagy puncta, and luciferase reporter system was used to determine binding ability between miR-34a and NEAT1 or putative targets. Additionally, indicated mRNAs and protein expressions were determined by qRT-PCR or western blotting, respectively. Results We found that NEAT1 expression was increased in CRC tissues and cells, which showed a negative correlation with miR-34a expression. In addition, NEAT1 knockdown noticeably inhibited the proliferation of CRC cells and enhanced 5-FU sensitivity. It revealed that NEAT1 knockdown suppressed the LC3 puncta and the expressions of Beclin-1, ULK1, and ratio of LC3II/I. Overexpression of miR-34a showed similar trends with NEAT1 knockdown. miR-34a was validated to target the putative binding sites in 3 '-UTR of HMGB1, ATG9A, and ATG4B, which are involved in the activation of autophagy. Inhibition of miR-34a or overexpression of HMGB1 could effectively reverse elevated 5-FU sensitivity upon NEAT1 knockdown. In addition, 3-MA reversed NEAT1 overexpression-induced resistance in HT29 cells. Conclusion These findings indicate that LncRNA NEAT1 could target miR-34a and promote autophagy to facilitate 5-FU chemoresistance in CRC.	[Liu, Fen; Ai, Fei-Yan; Zhang, De-Cai; Tian, Li; Yang, Zhen-Yun; Liu, Shao-Jun] Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, 138 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China; [Liu, Fen; Ai, Fei-Yan; Zhang, De-Cai] Hunan Key Lab Nonresolving Inflammat & Canc, Changsha, Hunan, Peoples R China		Liu, SJ (corresponding author), Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, 138 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.	cslsj169@163.com			Hunan Natural Science Foundation of Youth Fund Project [2018JJ3802]	This work was supported by Hunan Natural Science Foundation of Youth Fund Project (no. 2018JJ3802).	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FEB	2020	9	3					1079	1091		10.1002/cam4.2746		DEC 2019	13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	KH4IZ	WOS:000500541500001	31802650	gold, Green Published			2022-04-25	
J	Marion-Letellier, R; Raman, M; Savoye, G; Dechelotte, P; Ghosh, S				Marion-Letellier, Rachel; Raman, Maitreyi; Savoye, Guillaume; Dechelotte, Pierre; Ghosh, Subrata			Nutrient Modulation of Autophagy: Implications for Inflammatory Bowel Diseases	INFLAMMATORY BOWEL DISEASES			English	Article						autophagy; Crohn's disease; nutrients; PPAR-gamma	ACTIVATED-RECEPTOR-GAMMA; GENOME-WIDE ASSOCIATION; COLON-CANCER CELLS; CROHNS-DISEASE; FATTY-ACIDS; PPAR-GAMMA; DIFFERENTIAL MODULATION; SIGNALING PATHWAYS; DIETARY MODULATION; PROTEIN-SYNTHESIS	During nutrient deprivation, autophagy provides the constituents required to maintain the metabolism essential for survival. Recently, genome-wide association studies have identified genetic determinants for susceptibility to Crohn's disease (CD) such as ATG16L1 and IRGM that are involved in the autophagy pathway. Both disease-carrying NOD2 mutations and ATG16L1 mutations may result in impairment of autophagy. Impairment in autophagy results in impaired clearance of microbes. Ileal CD is associated with Paneth cell loss of function such as decreased production of alpha-defensins, which may arise from mutations in NOD2 or autophagy genes. Nutrients are able to modify several cellular pathways and in particular autophagy. We summarize the contribution of a variety of dietary components to activate autophagy. Understanding the crosstalk between nutrients and autophagy in the intestine may provide novel targets that have therapeutics potential in intestinal inflammation. Nutrient activation of autophagy may contribute to restoring the Paneth cell loss of function in ileal CD. 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Bowel Dis.	JAN	2013	19	1					205	212		10.1002/ibd.23001			8	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	109VL	WOS:000316397200032	23328774				2022-04-25	
J	Kopustinskiene, DM; Jakstas, V; Savickas, A; Bernatoniene, J				Kopustinskiene, Dalia M.; Jakstas, Valdas; Savickas, Arunas; Bernatoniene, Jurga			Flavonoids as Anticancer Agents	NUTRIENTS			English	Review						flavonoids; cancer; ROS; antioxidants; pro-oxidants; mitochondria	NF-KAPPA-B; ELECTRON-TRANSPORT CHAIN; MITOCHONDRIAL OXIDATIVE-PHOSPHORYLATION; HESPERETIN INDUCES APOPTOSIS; OVARIAN-CANCER CELLS; GREEN TEA CATECHINS; TOLL-LIKE RECEPTOR; HUMAN COLON-CANCER; GUT MICROBIOTA; ANTIOXIDANT CAPACITY	Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been shown to possess a wide variety of anticancer effects: they modulate reactive oxygen species (ROS)-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness. Flavonoids have dual action regarding ROS homeostasis-they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways. This article reviews the biochemical properties and bioavailability of flavonoids, their anticancer activity and its mechanisms of action.	[Kopustinskiene, Dalia M.; Jakstas, Valdas; Bernatoniene, Jurga] Lithuanian Univ Hlth Sci, Med Acad, Inst Pharmaceut Technol, Fac Pharm, LT-50161 Kaunas, Lithuania; [Jakstas, Valdas] Lithuanian Univ Hlth Sci, Med Acad, Dept Pharmacognosy, LT-50161 Kaunas, Lithuania; [Savickas, Arunas; Bernatoniene, Jurga] Lithuanian Univ Hlth Sci, Med Acad, Dept Drug Technol & Social Pharm, Fac Pharm, Sukileliu Pr 13, LT-50161 Kaunas, Lithuania		Bernatoniene, J (corresponding author), Lithuanian Univ Hlth Sci, Med Acad, Inst Pharmaceut Technol, Fac Pharm, LT-50161 Kaunas, Lithuania.; Bernatoniene, J (corresponding author), Lithuanian Univ Hlth Sci, Med Acad, Dept Drug Technol & Social Pharm, Fac Pharm, Sukileliu Pr 13, LT-50161 Kaunas, Lithuania.	DaliaMarija.Kopustinskiene@lsmuni.lt; Valdas.Jakstas@lsmuni.lt; Arunas.Savickas@lsmuni.lt; Jurga.Bernatoniene@lsmuni.lt		Jakstas, Valdas/0000-0001-7627-6263	Pharmaceutical and Health technology Open access center	The authors wish to thank Pharmaceutical and Health technology Open access center for support of this study.	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J	Wang, HS; Li, W; Xu, J; Zhang, T; Zuo, DQ; Zhou, ZF; Lin, BH; Wang, GY; Wang, ZY; Sun, W; Sun, MX; Chang, SM; Cai, ZD; Hua, YQ				Wang, Hongsheng; Li, Wen; Xu, Jing; Zhang, Tao; Zuo, Dongqing; Zhou, Zifei; Lin, Binhui; Wang, Gangyang; Wang, Zhuoying; Sun, Wei; Sun, Mengxiong; Chang, Shimin; Cai, Zhengdong; Hua, Yingqi			NDRG1 inhibition sensitizes osteosarcoma cells to combretastatin A-4 through targeting autophagy	CELL DEATH & DISEASE			English	Article							DOWNSTREAM-REGULATED GENE-1; COLON-CANCER CELLS; METASTASIS SUPPRESSOR; A4 PHOSPHATE; SIGNALING PATHWAYS; LUNG-CANCER; CHLOROQUINE; PROMOTES; PROTEIN; ANGIOGENESIS	Combretastatin A-4 (CA-4), a tubulin-depolymerizing agent, shows promising antitumor efficacy and has been under several clinical trials in solid tumors for 10 years. Autophagy has an important pro-survival role in cancer therapy, thus targeting autophagy may improve the efficacy of antitumor agents. N-myc downstream-regulated gene 1 (NDRG1) is a significant stress regulatory gene, which mediates cell survival and chemoresistance. Here we reported that CA-4 could induce cell-protective autophagy, and combination treatment of CA-4 and autophagy inhibitor chloroquine (CQ) exerted synergistic cytotoxic effect on human osteosarcoma (OS) cells. Meanwhile, CA-4 or CQ could increase the expression of NDRG1 independently. We further performed mechanistic study to explore how CA-4 and CQ regulate the expression of NDRG1. Using luciferase reporter assay, we found that CA-4 transcriptionally upregulated NDRG1 expression, whereas CQ triggered colocalization of NDRG1 and lysosome, which subsequently prevented lysosome-dependent degradation of NDRG1. Further, we showed that knockdown of NDRG1 caused the defect of lysosomal function, which accumulated LC3-positive autophagosomes by decreasing their fusion with lysosomes. Moreover, NDRG1 inhibition increased apoptosis in response to combination treatment with CA-4 and CQ. Taken together, our study revealed abrogation of NDRG1 expression sensitizes OS cells to CA-4 by suppression of autophagosome-lysosome fusion. These results provide clues for developing more effective cancer therapeutic strategies by the concomitant treatment with CA-4 and clinical available autophagy inhibitors.	[Wang, Hongsheng; Chang, Shimin] Tongji Univ, Yangpu Hosp, Dept Orthopaed, Shanghai 200090, Peoples R China; [Wang, Hongsheng; Xu, Jing; Zhang, Tao; Zuo, Dongqing; Zhou, Zifei; Lin, Binhui; Wang, Gangyang; Wang, Zhuoying; Sun, Wei; Sun, Mengxiong; Cai, Zhengdong; Hua, Yingqi] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Orthopaed, Shanghai, Peoples R China; [Li, Wen] Shanghai Univ Tradit Chinese Med, Municipal Hosp Tradit Chinese Med, Dept Oncol, Shanghai, Peoples R China; [Cai, Zhengdong; Hua, Yingqi] Shanghai Bone Tumor Inst, Shanghai, Peoples R China		Chang, SM; Cai, ZD; Hua, YQ (corresponding author), Tongji Univ, Yangpu Hosp, Dept Orthopaed, Shanghai 200090, Peoples R China.	shiminchang11@aliyun.com; czd856@vip.163.com; yhua@shsmu.edu.cn		Chang, Shimin/0000-0003-2691-7987	NSFCNational Natural Science Foundation of China (NSFC) [81202115]; Shanghai Municipal Commission of Health and Family Planning [XYQ2013108]; Shanghai Hospital Development Center [SHDC12013107]; School of Mesdicine, Shanghai Jiao Tong University [81450110092]; Shanghai Municipal Human Resources and Social Security Bureau [0403N14001]; Shanghai Charity cancer research center [0703N14012]; Shanghai Science and Technology CommissionShanghai Science & Technology CommitteeScience & Technology Commission of Shanghai Municipality (STCSM) [14140904000]	This work was supported by NSFC (81202115); the excellent young talent program of Shanghai Municipal Commission of Health and Family Planning (XYQ2013108); Research Grant from Shanghai Hospital Development Center (SHDC12013107), School of Mesdicine, Shanghai Jiao Tong University (81450110092), Shanghai Municipal Human Resources and Social Security Bureau (0403N14001), Shanghai Charity cancer research center (0703N14012) and Shanghai Science and Technology Commission (14140904000).	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SEP	2017	8								e3048	10.1038/cddis.2017.438			12	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	FI9KB	WOS:000412324800002	28906492	Green Published, gold			2022-04-25	
J	Zhang, YY; Xu, ZB; Sun, YW; Chi, P; Lu, XR				Zhang, Yiyi; Xu, Zongbin; Sun, Yanwu; Chi, Pan; Lu, Xingrong			Knockdown of KLK11 reverses oxaliplatin resistance by inhibiting proliferation and activating apoptosis via suppressing the PI3K/AKT signal pathway in colorectal cancer cell	ONCOTARGETS AND THERAPY			English	Article						colorectal cancer; kallikrein 11; oxaliplatin; drug resistance; apoptosis	KALLIKREIN-RELATED PEPTIDASES; HUMAN TISSUE KALLIKREINS; COLON-CANCER; EXPRESSION; GENE; SURVIVAL; CHEMORESISTANCE; CHEMOTHERAPY; AUTOPHAGY; PROSTATE	Introduction: Kallikrein 11 (KLK11) plays a crucial role in drug-resistance to oxaliplatin (L-OHP) in the treatment of metastatic colorectal cancer (mCRC). The study aimed to investigate the role of KLK11 in chemoresistance, and to clarify the mechanism underlying reverse of L-OHP resistance by knockdown of KLK11. Materials and Methods: Resistance to oxaliplatin was induced in HCT-8 (HCT-8/L-OHP) colorectal adenocarcinoma cell lines by exposing cells to increasing concentrations of L-OHP. MTT, RT-qPCR, and Western blot were used to evaluate the resistance to L-OHP. We then knocked down KLK11 in HCT-8/L-OHP cells to explore the mechanism through which KLK11 reverses L-OHP resistance. The mRNA and protein expression of KLK11 in tissues from mCRC patients were detected by RT-qPCR and immunohistochemistry. Results: The drug resistance index (RI) of HCT-8/L-OHP cell line to L-OHP, 5-Fluorouracil (5-FU), Irinotecan (CPT-11), Vincristine (VCR) and Cis-diamminedichloroplatinum (CDDP) were 10, 5.35, 3.23, 1.28, and 6.64, respectively. Increased expression of multi-drug resistant genes ABCC1, ABCB1, GSTP1 and ERCC1 were detected in HCT-8/L-OHP cell line. Moreover, the activated PI3K/AKT pathway was related to L-OHP-resistance. Knockdown of KLK11 in HCT-8/L-OHP cell reversed L-OHP-resistance by inhibiting cell growth and activating apoptosis via suppressing the PI3K/AKT signaling pathway. Moreover, high expression of KLK11 in chemoresistant-patients was associated with lymph node metastases and histopathology. Conclusion: KLK11 was highly expressed in chemoresistant-patients and L-OHP-resistant cell lines. Moreover, L-OHP resistance was associated with activated PI3K/AKT signal pathway. Knockdown of KLK11 can reverse L-OHP resistance by blocking PI3K/AKT signaling pathway.	[Zhang, Yiyi; Xu, Zongbin; Sun, Yanwu; Chi, Pan; Lu, Xingrong] Fujian Med Univ, Dept Colorectal Surg, Union Hosp, 29 Xinquan Rd, Fuzhou 350001, Fujian, Peoples R China		Chi, P; Lu, XR (corresponding author), Fujian Med Univ, Dept Colorectal Surg, Union Hosp, 29 Xinquan Rd, Fuzhou 350001, Fujian, Peoples R China.	chipan363@163.com; fjxhlxr@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472777]; Training Plan of Middle-aged and Young Talents of Fujian Province Health and Family Planning Commission [2013-ZQN-ZD-11]; Science Foundation of the Fujian ProvinceNatural Science Foundation of Fujian Province [2017J01296]; National Clinical Key Specialty Construction Project (General Surgery) of China [2012-649]	This study was supported by the National Natural Science Foundation of China (No 81472777), Training Plan of Middle-aged and Young Talents of Fujian Province Health and Family Planning Commission (No 2013-ZQN-ZD-11), Science Foundation of the Fujian Province, (No 2017J01296), and National Clinical Key Specialty Construction Project (General Surgery) of China (No 2012-649).	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J	Liu, LY; Zhang, JL; Liu, HD; Shi, M; Zhang, J; Chen, L; Huang, LQ; Li, B; Xu, P				Liu, Liyan; Zhang, Jilin; Liu, Hongdong; Shi, Min; Zhang, Jie; Chen, Li; Huang, Luqi; Li, Bin; Xu, Peng			Correlation of autophagy-related genes for predicting clinical prognosis in colorectal cancer	BIOMARKERS IN MEDICINE			English	Article						ARGs; autophagy; autophagy-related genes; clinical prognosis; colorectal cancer; gene ontology; KEGG; Kyoto Encyclopedia of Genes and Genomes; TCGA; The Cancer Genome Atlas	BIOLOGICAL FUNCTIONS; CELL BIOLOGY; COLON-CANCER; INVASION; BECLIN-1; LC3; IDENTIFICATION; PROLIFERATION; ACTIVATION; MECHANISMS	Aim: Autophagy plays a controversial role in cancer. The role of autophagy-related genes (ARGs) in colorectal cancer (CRC) was evaluated based on publicly available data from The Cancer Genome Atlas and the Human Autophagy Database. Materials & methods: After collecting CRC-related transcript and clinical data and a list of ARGs from public databases, the Wilcoxon test was used to identify the differentially expressed ARGs between CRC and paired normal tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to identify the major biological properties and pathways associated with these genes. Univariate Cox regression was used to identify the prognosis-associated ARGs, and a forest plot was used to visualize the results. Kaplan-Meier analysis of the 5-year survival rate was performed. Univariate and multivariate Cox analyses were used to verify the impact of the prognosis-associated ARGs. Results: A total of 36 differentially expressed genes (16 upregulated and 20 downregulated in CRC) were obtained from among 206 ARGs. There were 53 enriched pathways, including the p53 signaling pathway, platinum drug resistance, apoptosis, EGFR tyrosine kinase inhibitor resistance and ErbB signaling pathway (p- and q-values <0.05). Kaplan-Meier analysis showed that the 5-year survival rate was 46.0% (95% CI: 0.335-0.631) and 76.0% (95% CI: 0.651-0.886) in the high- and low-risk groups, respectively. The high-risk patients had worse survival probability (p = 6.256 x 10(-5)). Independent-samples t-tests revealed that MAP1LC3C expression was higher in patients aged <= 65 than >65 (p = 0.022); RAB7A expression was higher in patients aged <= 65 than >65 (p = 7.31 x 10(-4)), higher in M1 than M0 (p = 0.042), higher in N1-3 than N0 (p = 0.002) and higher in stage III and IV than I and II (p = 0.042); risk score was higher in N1-3 than N0 (p = 0.001) and in stage III and IV than I and II (p = 0.002); and WIPI2 expression was higher in M1 than M0 (p = 0.002), higher in N1-3 than N0 (p = 2.059 x 10(-7)) and higher in stage III and IV than I and II (p = 2.299 x 10(-7)). There were no differences in risk score between males and females (p = 0.593), T1-2 and T3-4 (p = 0.082) or M0 and M1 (p = 0.072). Univariate and multivariate Cox analyses showed that RAB7A was a lower-risk gene, while MAP1LC3C, WIPI2, DAPK1, ULK3 and PELP1 were high-risk genes. Conclusion: Certain ARGs are potential prognostic molecular markers of poor prognosis in CRC. Additionally, the p53 signaling pathway, platinum drug resistance, apoptosis, EGFR tyrosine kinase inhibitor resistance and ErbB signaling pathway may be critical pathways regulated by ARGs in CRC.	[Liu, Liyan] Jiangxi Canc Hosp, Dept Pharm, 519 Beijing East Rd, Nanchang 330029, Jiangxi, Peoples R China; [Liu, Liyan] Nanchang Univ, Affiliated Canc Hosp, Dept Pharm, 519 Beijing East Rd, Nanchang 330029, Jiangxi, Peoples R China; [Liu, Liyan; Liu, Hongdong; Shi, Min; Zhang, Jie; Li, Bin; Xu, Peng] Jiangxi Univ Tradit Chinese Med, Coll Tradit Chinese Med, Workstat Acad, Lab Anim Sci & Technol Ctr, 1688 Meiling Rd, Nanchang 330004, Jiangxi, Peoples R China; [Zhang, Jilin] Jiangxi Prov Peoples Hosp, Dept Tradit Chinese Med, 92 Aiguo Rd, Nanchang 330006, Jiangxi, Peoples R China; [Zhang, Jie] Chengdu Univ Tradit Chinese Med, Coll Pharm, 1166 Liutai Ave, Chengdu 611137, Peoples R China; [Huang, Luqi] China Acad Chinese Med Sci, Natl Resource Ctr Chinese Mat Med, State Key Lab Breeding Base Daodi Herbs, 16 Nanxiao St, Beijing 100700, Peoples R China		Li, B; Xu, P (corresponding author), Jiangxi Univ Tradit Chinese Med, Coll Tradit Chinese Med, Workstat Acad, Lab Anim Sci & Technol Ctr, 1688 Meiling Rd, Nanchang 330004, Jiangxi, Peoples R China.	lbin@crjz.com; xp0420@163.com			Projects of Increase and Decrease of Central Level Major [2060302]; Workstation Project of Jiangxi University of Traditional Chinese Medicine [YSGZZ201801]; First-Class Subject Project of Jiangxi University of Traditional Chinese Medicine [JXSYLXK-ZHYAO144]; Chinese Medicine Science and Technology Project of the Health Commission of Jiangxi Province [2014A026, 2018A310]	This study was supported by the Projects of Increase and Decrease of Central Level Major (2060302), the Workstation Project of Jiangxi University of Traditional Chinese Medicine (YSGZZ201801), the First-Class Subject Project of Jiangxi University of Traditional Chinese Medicine (JXSYLXK-ZHYAO144) and the Chinese Medicine Science and Technology Project of the Health Commission of Jiangxi Province (2014A026, 2018A310). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subjectmatter ormaterials discussed in the manuscript apart from those disclosed.	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Med.	JUN	2021	15	10					715	729		10.2217/bmm-2020-0292		JUN 2021	15	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	TC4IC	WOS:000665759300002	34169735				2022-04-25	
J	Si, YR; Yang, ZG; Ge, QX; Yu, LB; Yao, MY; Sun, XF; Ren, Z; Ding, CS				Si, Yaoran; Yang, Zhaoguo; Ge, Quanxing; Yu, Lingbing; Yao, Meiying; Sun, Xinfang; Ren, Zheng; Ding, Chunsheng			Long non-coding RNA Malat1 activated autophagy, hence promoting cell proliferation and inhibiting apoptosis by sponging miR-101 in colorectal cancer	CELLULAR & MOLECULAR BIOLOGY LETTERS			English	Article						Colorectal cancer; Long noncoding RNA Malat1; Autophagy; Proliferation; Apoptosis; miR-101	LNCRNA MALAT1; METASTASIS; EXPRESSION; CROSSTALK	BackgroundLong non-coding RNA Malat1 has been widely identified as an oncogene which shows a significant relationship with tumorigenesis in colorectal cancer (CRC). Nonetheless, whether Malat1 participates in the autophagy of colorectal cancer remains unclear.Materials and methodsFirst, the expression level of Malat1 in 96 pairs of colorectal cancer tissues and four cell lines was detected by qRT-PCR. Subsequently, the autophagy activity in colorectal cancer tissues and cell lines was detected by western blot. Furthermore, the CCK-8 assay and flow cytometry (FCM) were performed to detect the role of autophagy activated by Malat1 in colorectal cancer cell lines.ResultsIn this study, significantly increased Malat1 expression and autophagy activity were found in colorectal cancer tissues compared with the adjacent normal tissues. Also, the Malat1 level was positively correlated with the expression of LC3-II mRNA in vivo. Moreover, autophagy activation and cell proliferation were significantly facilitated by Malat1 in colorectal cancer cells, while apoptosis decreased. Above all, the inhibition of autophagy by 3-MA not only relieved the Malat1-induced cell proliferation but also promoted the Malat1-induced cell apoptosis. In addition, Malat1 was found to act as an endogenous sponge by directly binding to miR-101 to reduce miR-101. Furthermore, the suppressive effects of miR-101 on the autophagy, proliferation, and apoptosis of CRC were abolished by Malat1.ConclusionLong non-coding RNA Malat1 activated autophagy and promoted cell proliferation, yet inhibited apoptosis by sponging miR-101 in colorectal cancer cells.	[Si, Yaoran; Ge, Quanxing; Yu, Lingbing; Yao, Meiying; Sun, Xinfang; Ren, Zheng; Ding, Chunsheng] Henan Univ, Huaihe Hosp, Dept Gastroenterol, Kaifeng 475000, Henan, Peoples R China; [Yang, Zhaoguo] Kaifeng Cent Hosp, Dept Gen Surg, Kaifeng, Henan, Peoples R China		Ding, CS (corresponding author), Henan Univ, Huaihe Hosp, Dept Gastroenterol, Kaifeng 475000, Henan, Peoples R China.	ding_chunsheng@yeah.net			Henan Science and Technology Development Plan Project [182102310367]	Henan Science and Technology Development Plan Project: 182102310367.	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J	Pirol, SC; Caliskan, B; Durmaz, I; Atalay, R; Banoglu, E				Pirol, Seyma Cankara; Caliskan, Burcu; Durmaz, Irem; Atalay, Rengul; Banoglu, Erden			Synthesis and preliminary mechanistic evaluation of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid amides with potent antiproliferative activity on human cancer cell lines	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY			English	Article						Diarylpyrazole; Quinoline; Cytotoxicity; Autophagy; Apoptosis	BIOLOGICAL EVALUATION; PYRAZOLE DERIVATIVES; HYDRAZONE DERIVATIVES; DISCOVERY; APOPTOSIS; AUTOPHAGY; INHIBITORS; AGENTS; LC3	We synthesized a series of novel amide derivatives of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid and assessed their antiproliferative activities against three human cancer cell lines (Huh7, human liver; MCF7, breast and HCT116, colon carcinoma cell lines) with the sulforhodamine B assay. Compound 4j with 2-chloro-4-pyridinyl group in the amide part exhibited promising cytotoxic activity against all cell lines with IC50 values of 1.6 mu M, 3.3 mu M and 1.1 mu M for Huh7. MCF7 and HCT116 cells, respectively, and produced dramatic cell cycle arrest at SubG1/G1 phase as an indicator of apoptotic cell death induction. On the basis of their high potency in cellular environment, these straightforward pyrazole-3-carboxamide derivatives may possess potential in the design of more potent compounds for intervention with cancer cell proliferation. (C) 2014 Elsevier Masson SAS. All rights reserved.	[Pirol, Seyma Cankara; Caliskan, Burcu; Banoglu, Erden] Gazi Univ, Fac Pharm, Dept Pharmaceut Chem, TR-06330 Ankara, Turkey; [Durmaz, Irem; Atalay, Rengul] Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, Turkey; [Atalay, Rengul] Bilkent Univ, Genet & Biotechnol Res Ctr BilGen, TR-06800 Ankara, Turkey		Banoglu, E (corresponding author), Gazi Univ, Fac Pharm, Dept Pharmaceut Chem, TR-06330 Ankara, Turkey.	ebanoglu@gmail.com	Banoglu, Erden/W-2131-2017; Caliskan, Burcu/AAD-1957-2019; Cetin-Atalay, Rengul/O-9826-2014; Sahin, Irem Durmaz/A-3501-2019; Çalışkan, Burcu/AAF-9101-2021	Banoglu, Erden/0000-0003-4737-1733; Caliskan, Burcu/0000-0003-2391-5644; Cetin-Atalay, Rengul/0000-0003-2408-6606; Sahin, Irem Durmaz/0000-0001-5037-7883; 	Gazi UniversityGazi University [BAP 02/2011-44]; Turkish Academy of Sciences (TUBA)Turkish Academy of Sciences	This work was supported by Gazi University (BAP 02/2011-44) and partly supported by Turkish Academy of Sciences (TUBA).	Caliskan B., 2013, MED CHEM RES, V22, P782; Dickson MA, 2009, CURR ONCOL, V16, P120; Ding XL, 2009, BIOORG MED CHEM LETT, V19, P5325, DOI 10.1016/j.bmcl.2009.07.131; El-Deeb IM, 2010, BIOORGAN MED CHEM, V18, P3961, DOI 10.1016/j.bmc.2010.04.029; El-Gamal MI, 2013, CHEM BIOL DRUG DES, V82, P336, DOI 10.1111/cbdd.12186; Farag AM, 2010, EUR J MED CHEM, V45, P5887, DOI 10.1016/j.ejmech.2010.09.054; Gupta LK, 2007, SPECTROCHIM ACTA A, V66, P972, DOI 10.1016/j.saa.2006.04.035; Jin CH, 2011, BIOORG MED CHEM LETT, V21, P6049, DOI 10.1016/j.bmcl.2011.08.064; Jin CH, 2011, EUR J MED CHEM, V46, P3917, DOI 10.1016/j.ejmech.2011.05.063; Jin CH, 2011, BIOORGAN MED CHEM, V19, P2633, DOI 10.1016/j.bmc.2011.03.008; Keter FK, 2012, BIOMETALS, V25, P9, DOI 10.1007/s10534-011-9496-4; Kim D.K., 2010, BIOORGAN MED CHEM, V18, P4459; Kumar H, 2013, EUR J MED CHEM, V70, P248, DOI 10.1016/j.ejmech.2013.10.004; Levent S, 2013, EUR J MED CHEM, V64, P42, DOI 10.1016/j.ejmech.2013.03.048; Lian S, 2009, BIOORGAN MED CHEM, V17, P7085, DOI 10.1016/j.bmc.2009.09.004; Maurin C, 2004, TETRAHEDRON, V60, P6479, DOI 10.1016/j.tet.2004.06.030; Nitulescu GM, 2010, EUR J MED CHEM, V45, P4914, DOI 10.1016/j.ejmech.2010.07.064; OEFINGER PE, 1981, J GEN VIROL, V53, P105, DOI 10.1099/0022-1317-53-1-105; Scherz-Shouval R, 2010, P NATL ACAD SCI USA, V107, P18511, DOI 10.1073/pnas.1006124107; Schwartz GK, 2005, J CLIN ONCOL, V23, P9408, DOI 10.1200/JCO.2005.01.5594; Shoemaker RH, 2006, NAT REV CANCER, V6, P813, DOI 10.1038/nrc1951; Tanida Isei, 2008, V445, P77, DOI 10.1007/978-1-59745-157-4_4; Wei F, 2006, BIOORG MED CHEM LETT, V16, P6342, DOI 10.1016/j.bmcl.2006.09.008; Xia Y, 2007, BIOORGAN MED CHEM, V15, P6893, DOI 10.1016/j.bmc.2007.08.021; Xia Y, 2008, EUR J MED CHEM, V43, P2347, DOI 10.1016/j.ejmech.2008.01.021; Zheng LW, 2010, BIOORG MED CHEM LETT, V20, P4766, DOI 10.1016/j.bmcl.2010.06.121; Zheng LW, 2009, BIOORGAN MED CHEM, V17, P1957, DOI 10.1016/j.bmc.2009.01.037	27	39	39	3	24	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER	ISSY-LES-MOULINEAUX	65 RUE CAMILLE DESMOULINS, CS50083, 92442 ISSY-LES-MOULINEAUX, FRANCE	0223-5234	1768-3254		EUR J MED CHEM	Eur. J. Med. Chem.	NOV 24	2014	87						140	149		10.1016/j.ejmech.2014.09.056			10	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)	Pharmacology & Pharmacy	CU3NE	WOS:000363431300013	25247770	Green Published			2022-04-25	
J	Zhang, XN; Fryknas, M; Hernlund, E; Fayad, W; De Milito, A; Olofsson, MH; Gogvadze, V; Dang, L; Pahlman, S; Schughart, LAK; Rickardson, L; Darcy, P; Gullbo, J; Nygren, P; Larsson, R; Linder, S				Zhang, Xiaonan; Fryknas, Marten; Hernlund, Emma; Fayad, Walid; De Milito, Angelo; Olofsson, Maria Hagg; Gogvadze, Vladimir; Dang, Long; Pahlman, Sven; Schughart, Leoni A. Kunz; Rickardson, Linda; Darcy, Padraig; Gullbo, Joachim; Nygren, Peter; Larsson, Rolf; Linder, Stig			Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments	NATURE COMMUNICATIONS			English	Article							CANCER-CELLS; IN-SITU; HYPOXIA; METFORMIN; SPHEROIDS; GROWTH; AUTOPHAGY; THERAPY; COMPLEX; RHODAMINE-123	Abnormal vascularization of solid tumours results in the development of microenvironments deprived of oxygen and nutrients that harbour slowly growing and metabolically stressed cells. Such cells display enhanced resistance to standard chemotherapeutic agents and repopulate tumours after therapy. Here we identify the small molecule VLX600 as a drug that is preferentially active against quiescent cells in colon cancer 3-D microtissues. The anticancer activity is associated with reduced mitochondrial respiration, leading to bioenergetic catastrophe and tumour cell death. VLX600 shows enhanced cytotoxic activity under conditions of nutrient starvation. Importantly, VLX600 displays tumour growth inhibition in vivo. Our findings suggest that tumour cells in metabolically compromised microenvironments have a limited ability to respond to decreased mitochondrial function, and suggest a strategy for targeting the quiescent populations of tumour cells for improved cancer treatment.	[Zhang, Xiaonan; Hernlund, Emma; Fayad, Walid; De Milito, Angelo; Olofsson, Maria Hagg; Darcy, Padraig; Linder, Stig] Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden; [Fryknas, Marten; Rickardson, Linda; Gullbo, Joachim; Larsson, Rolf; Linder, Stig] Uppsala Univ, Div Clin Pharmacol, Dept Med Sci, S-75185 Uppsala, Sweden; [Gogvadze, Vladimir] Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden; [Dang, Long] Univ Florida, Shands Canc Ctr, Div Hematol Oncol, Dept Internal Med, Gainesville, FL 32601 USA; [Pahlman, Sven] Lund Univ, Skane Univ Hosp, Dept Lab Med, Ctr Mol Pathol,CREATE Hlth, S-20502 Malmo, Sweden; [Schughart, Leoni A. Kunz] Tech Univ Dresden, OncoRay Natl Ctr Radiat Res Oncol, D-01307 Dresden, Germany; [Gullbo, Joachim; Nygren, Peter] Uppsala Univ, Div Oncol, Dept Radiol Oncol & Radiat Sci, S-75185 Uppsala, Sweden		Linder, S (corresponding author), Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden.	Stig.Linder@ki.se	Gogvadze, Vladimir/A-4392-2014; D'Arcy, Pádraig/AAB-5045-2019; D'Arcy, Pádraig/F-7633-2018; Fayad, Walid M. O. H./O-7269-2018	D'Arcy, Pádraig/0000-0001-6671-7600; D'Arcy, Pádraig/0000-0001-6671-7600; Fayad, Walid M. O. H./0000-0002-7975-0343; De Milito, Angelo/0000-0003-2591-2914	Cancerfonden, Radiumhemmets Forskningsfonder, Vetenskapsradet; Alex and Eva Wallstrom Foundation; Lions Cancer Research Fund; Strategiska Forskningsstiftelsen (S.S.F.)	This work was supported by Cancerfonden, Radiumhemmets Forskningsfonder, Vetenskapsradet, the Alex and Eva Wallstrom Foundation, the Lions Cancer Research Fund and Strategiska Forskningsstiftelsen (S.S.F.). We are grateful to Hans Rosen, Vivolux AB, for continuous support and management of projects, Maria Rydaker, Lena Lenhammar and Christina Leek, Hanna Goransson Kultima and the Uppsala Array platform for excellent technical support and Ingrid Holmberg for artwork.	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Commun.	FEB	2014	5								3295	10.1038/ncomms4295			14	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	AC6WX	WOS:000332667600042	24548894	hybrid, Green Published			2022-04-25	
J	Wang, F; Song, ZY; Qu, XJ; Li, F; Zhang, L; Li, WB; Cui, SX				Wang, Feng; Song, Zhi-Yu; Qu, Xian-Jun; Li, Feng; Zhang, Liang; Li, Wen-Bao; Cui, Shu-Xiang			M10, a novel derivative of Myricetin, prevents ulcerative colitis and colorectal tumor through attenuating robust endoplasmic reticulum stress	CARCINOGENESIS			English	Article							UNFOLDED PROTEIN RESPONSE; INFLAMMATION; DISEASE; CELLS; ER; CANCER; RISK	Chronic gut inflammation disposes to an increased risk of colitis-associated cancer. Chemoprevention is an attractive complementary strategy. We aimed to evaluate the chemopreventive effects of M10, a novel derivative of Myricetin, in the murine azoxymethane/dextran sodium sulfate model. Oral administration of M10 at 50-100 mg/kg once a day for consecutive 12 weeks significantly prevented ulcerative colitis (UC) and colorectal tumor. Pathological analysis of intestines showed that M10 reduced the degree of chronic inflammation and prevented the progression of colorectal tumorigenesis. Flow cytometry analysis of the immunocytes isolated from intraepithelial and lamina propria showed that M10 prevented the infiltration of myeloid-derived suppressor cells and increased CD8(+)T and CD4(+)T cells in colorectal tissues. Enzyme-linked immunosorbent analysis revealed the reduction of pro-inflammatory mediators granulocyte-macrophage colony-stimulating factor/macrophage colony-stimulating factor, IL-6 and TNF-alpha in colonic mucosa. Western blot assay also showed M10 prevention of the NF-kappa B/IL-6/STAT3 pathways and the biomarkers of inflammation and colorectal tumorigenesis. Electron microscopy analysis revealed that M10 prevent robust endoplasmic reticulum (ER) stress-induced autophagy in inflamed colonic mucosal cells. In conclusion, oral administration of Myricetin derivative M10 exerts chemoprevention of UC and colorectal tumor in mice. The mechanism of chemoprevention is associated with the reduction of biomarkers of chronic inflammation and proliferation through attenuating robust ER stress in inflamed colonic mucosal cells. M10 exerts chemoprevention activity without evidence of toxicity in mice. These results justify further evaluation of M10 in clinical trials. M10 could develop a promising regimen in the chemoprevention of colitis and colorectal cancer.	[Wang, Feng; Cui, Shu-Xiang] Capital Med Univ, Sch Publ Hlth, Dept Toxicol & Sanit Chem, Beijing Key Lab Environm Toxicol, Beijing, Peoples R China; [Song, Zhi-Yu; Qu, Xian-Jun] Capital Med Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing, Peoples R China; [Li, Feng; Zhang, Liang; Li, Wen-Bao] Marine Biomed Res Inst Qingdao, Dept Med Chem, Qingdao, Shandong, Peoples R China		Cui, SX (corresponding author), Capital Med Univ, Sch Publ Hlth, Dept Toxicol & Sanit Chem, Beijing Key Lab Environm Toxicol, Beijing, Peoples R China.; Li, WB (corresponding author), Marine Biomed Res Inst Qingdao, Dept Med Chem, Qingdao, Shandong, Peoples R China.	wbli92128@163.com; sxccui@ccmu.edu.cn			Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81673449, 91629303]; Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of EducationBeijing Natural Science Foundation [KZ201710025020, KZ201810025033]	This work was supported by Natural Science Foundation of China (81673449, 91629303) and Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ201710025020, KZ201810025033).	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J	Mao, XH; Zhang, X; Zheng, XW; Chen, YW; Xuan, ZX; Huang, P				Mao, Xiaohong; Zhang, Xin; Zheng, Xiaowei; Chen, Yongwu; Xuan, Zixue; Huang, Ping			Curcumin suppresses LGR5(+) colorectal cancer stem cells by inducing autophagy and via repressing TFAP2A-mediated ECM pathway	JOURNAL OF NATURAL MEDICINES			English	Article						Colorectal cancer; Curcumin; Cancer stem cells; Autophagy; LGR5; TFAP2A		Colorectal cancer stem cells (CSCs) have the potential for self-renewal, proliferation, and differentiation. And LGR5 is a stem cell marker gene of colorectal cancer. Curcumin can suppress oncogenicity of many cancer cells, yet the effect and mechanism of curcumin in LGR5(+) colorectal cancer stem cells (CSCs) have not been studied. In this study, we studied the effect of curcumin on LGR5(+) colorectal CSCs using the experiments of tumorsphere formation, cell viability and cell apoptosis. Then autophagy analysis, RNA-Seq, and real-time PCR were used to identify the mechanism responsible for the inhibition of LGR5(+) colorectal CSCs. Our results showed that curcumin inhibited tumorsphere formation, decreased cell viability in a dose-dependent manner, and also promoted apoptosis of LGR5(+) colorectal CSCs. Next, we found curcumin induced autophagy of LGR5(+) colorectal CSCs. When LGR5(+) colorectal CSCs were co-treated with curcumin and the autophagy inhibitor (hydroxychloroquine), curcumin-induced cell proliferation inhibition decreased. In addition, we also found that curcumin inhibited the extracellular matrix (ECM)-receptor interaction pathway via the downregulation of the following genes: GP1BB, COL9A3, COMP, AGRN, ITGB4, LAMA5, COL2A1, ITGB6, ITGA1, and TNC. Further, these genes were transcriptionally regulated by TFAP2A, and the high expression of TFAP2A was associated with poor prognosis in colorectal cancer. In conclusion, curcumin suppressed LGR5(+) colorectal CSCs, potentially by inducing autophagy and repressing the oncogenic TFAP2A-mediated ECM pathway. Graphic abstract	[Mao, Xiaohong; Xuan, Zixue; Huang, Ping] Hangzhou Med Coll, Dept Pharm, Zhejiang Prov Peoples Hosp, Peoples Hosp, Hangzhou 310014, Peoples R China; [Zhang, Xin] Hangzhou Med Coll, Dept Pathol, Zhejiang Prov Peoples Hosp, Peoples Hosp, Hangzhou 310014, Peoples R China; [Zheng, Xiaowei] Zhejiang Canc Hosp, Dept Pharm, Hangzhou 310022, Peoples R China; [Chen, Yongwu] Univ Sci & Technol China, Dept Pharm, Div Life Sci & Med, Affiliated Hosp 1, Hefei 230036, Peoples R China		Xuan, ZX; Huang, P (corresponding author), Hangzhou Med Coll, Dept Pharm, Zhejiang Prov Peoples Hosp, Peoples Hosp, Hangzhou 310014, Peoples R China.	xuanzixue0222@163.com; huangping_zry@163.com		Xuan, Zi-xue/0000-0002-6296-4062	Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LY19H280007, LQ17H310002]; Zhejiang Medical Technology Plan Project [2017ZD003, 2019KY027]	This study was supported by Natural Science Foundation of Zhejiang Province (Grant Nos. LY19H280007 and LQ17H310002) and Zhejiang Medical Technology Plan Project (Grant Nos. 2017ZD003 and 2019KY027).	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Nat. Med.	JUN	2021	75	3					590	601		10.1007/s11418-021-01505-1		MAR 2021	12	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	SJ7GX	WOS:000628459300001	33713277	Green Published, hybrid			2022-04-25	
J	Yu, DH; Zhang, X; Wang, H; Zhang, L; Chen, H; Hu, M; Dong, Z; Zhu, G; Qian, Z; Fan, J; Su, X; Xu, Y; Zheng, L; Dong, H; Yin, X; Ji, Q; Ji, J				Yu, D-H; Zhang, X.; Wang, H.; Zhang, L.; Chen, H.; Hu, M.; Dong, Z.; Zhu, G.; Qian, Z.; Fan, J.; Su, X.; Xu, Y.; Zheng, L.; Dong, H.; Yin, X.; Ji, Q.; Ji, J.			The essential role of TNIK gene amplification in gastric cancer growth	ONCOGENESIS			English	Article						gastric cancer; TNIK; Wnt	NCK-INTERACTING KINASE; SIGNAL-TRANSDUCTION; WNT; CYTOSKELETON; APOPTOSIS; AUTOPHAGY; PATHWAY	Traf2- and Nck-interacting kinase (TNIK) is one of the germinal center kinase family members involved in cytoskeleton organization and neuronal dendrite extension. Emerging evidence supports that TNIK is essential for activation of WNT signaling pathway in colon cancer growth. To search for novel genetic aberrations that drive carcinogenesis, we performed microarray-based comparative hybridization assay for gene copy number variations in primary tumor samples. Our data showed that TNIK gene was amplified in 7% (8/106) of Chinese gastric cancer patients. Theses amplifications were confirmed by fluorescence in situ hybridization analysis. PAMC82 human gastric cancer and T47D human breast cancer cell lines with TNIK amplification were identified to further understand the function of TNIK gene amplification. RNA-interference-mediated silencing of TNIK resulted in significant inhibition of cell growth and induction of cell death in TNIK-amplified, but not in TNIK-non-amplified, cell lines tested. This selective sensitivity to the TNIK inhibition was also observed under the effect of a small-molecule TNIK inhibitor. Furthermore, our data indicated that TNIK's role in gastric cancer growth was not dependent on Wnt signaling but rather was involved in AKT activation and cell autophagy. Together, our results suggest that TNIK is a novel therapeutic target in gastric cancer and TNIK amplification can be potentially used for patient selection.	[Yu, D-H; Zhang, X.; Wang, H.; Hu, M.; Dong, Z.; Zhu, G.; Qian, Z.; Fan, J.; Su, X.; Xu, Y.; Zheng, L.; Dong, H.; Yin, X.; Ji, Q.] AstraZeneca, Innovat Ctr China, Shanghai, Peoples R China; [Wang, H.] Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China; [Zhang, L.; Ji, J.] Peking Univ Canc Hosp & Inst, Dept Surg, Key Lab Carcinogenesis & Translat Res, Minist Educ, Beijing 10042, Peoples R China; [Chen, H.] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Gen Surg, Shanghai 200030, Peoples R China		Yu, DH (corresponding author), Astrazeneca, Biosci, 199 Liangjing Rd,Zhangjiang High Tech Pk, Shangha 201203, Peoples R China.	yudehua@yahoo.com; jiafuj@gmail.com		JI, JIAFU/0000-0001-6878-5543			Anastas JN, 2013, NAT REV CANCER, V13, P11, DOI 10.1038/nrc3419; Fu CA, 1999, J BIOL CHEM, V274, P30729, DOI 10.1074/jbc.274.43.30729; Ho KK, 2013, BIOORG MED CHEM LETT, V23, P569, DOI 10.1016/j.bmcl.2012.11.013; Hussain NK, 2010, J NEUROSCI, V30, P14786, DOI 10.1523/JNEUROSCI.4124-10.2010; Kawabe H, 2010, NEURON, V65, P358, DOI 10.1016/j.neuron.2010.01.007; Li J, 2013, J TRANSL MED, V11, DOI 10.1186/1479-5876-11-241; Mahmoudi T, 2009, EMBO J, V28, P3329, DOI 10.1038/emboj.2009.285; Maiese K, 2012, EXPERT OPIN THER TAR, V16, P1203, DOI 10.1517/14728222.2012.719499; Nusse R, 2012, EMBO J, V31, P2670, DOI 10.1038/emboj.2012.146; Parkhitko AA, 2013, BIOCHEMISTRY-MOSCOW+, V78, P355, DOI 10.1134/S0006297913040044; Pecina-Slaus N, 2010, CANCER CELL INT, V10, DOI 10.1186/1475-2867-10-22; Saito-Diaz K, 2013, GROWTH FACTORS, V31, P1, DOI 10.3109/08977194.2012.752737; Shitashige M, 2010, CANCER RES, V70, P5024, DOI 10.1158/0008-5472.CAN-10-0306; Shkoda A, 2012, PLOS BIOL, V10, DOI 10.1371/journal.pbio.1001376; Taira K, 2004, J BIOL CHEM, V279, P49488, DOI 10.1074/jbc.M406370200; Xie L, 2013, CLIN CANCER RES, V19, P2572, DOI 10.1158/1078-0432.CCR-12-3898; Yamada T., 2010, United States Patent, Patent No. [WO2010064111, 2010064111]	17	20	20	2	6	NATURE PUBLISHING GROUP	NEW YORK	75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA	2157-9024			ONCOGENESIS	Oncogenesis	FEB	2014	3								e89	10.1038/oncsis.2014.2			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	AZ8CU	WOS:000348443300005	24566388	Green Published, gold			2022-04-25	
J	Yang, JW; Zhang, QH; Liu, T				Yang, Jing-wen; Zhang, Qing-huai; Liu, Tong			Autophagy facilitates anticancer effect of 5-fluorouracil in HCT-116 cells	JOURNAL OF CANCER RESEARCH AND THERAPEUTICS			English	Article						Apoptosis; autophagy; chemotherapy; p53	CANCER; CHEMOTHERAPY; INHIBITION; PUERARIN; PATHWAY	Aim of Study: The roles of autophagy performed in chemotherapy-induced cell death or proliferation inhibition were still in debate. In this study, we aimed to disclose the function of autophagy in chemotherapy of HCT-116 colon cells. Materials and Methods: Pharmacological and genetic methods were applied to induce and inhibit autophagy and elucidate the roles of autophagy performed in chemotherapy-induced proliferation inhibition and apoptosis. Autophagy was assessed by microtubule-associated protein light chain 3 (LC3) expression and monodansylcadaverine (MDC) staining. Results: After treatment with 5-fluorouracil (5-FU), HCT-116 cells showed typical autophagy as stained by MDC. Autophagy inhibitor (3-methyladenine [3-MA]) or inducer (rapamycin) was applied in combination with 5-FU, respectively. As evidenced by our data, 3-MA inhibited while rapamycin facilitated 5-FU-induced apoptosis and proliferation inhibition of HCT-116 cells. Consistently, 3-MA inhibited, while rapamycin facilitated 5-FU-induced expressions of Beclin1 and LC3B. Moreover, 3-MA inhibited while rapamycin facilitated 5-FU-induced p53 protein expression. Using genetic method, Beclin1 overexpression increased while Beclin1 knockdown decreased 5-FU-induced cell proliferation inhibition and apoptosis. Especially, Beclin1 overexpression increased while Beclin1 knockdown decreased 5-FU-induced p53 expression. Conclusion: Our study provides both of pharmacological and genetic evidence to support that autophagy facilitates anticancer effect of the chemotherapeutic agent. The associated application of autophagy inducer with 5-FU would be beneficial for the chemotherapy in HCT-116 cancer cells.	[Yang, Jing-wen; Zhang, Qing-huai] Tianjin Union Med Ctr, Dept Anorectal Surg, Tianjin, Peoples R China; [Liu, Tong] Tianjin Med Univ, Gen Hosp, Dept Gen Surg, Inst Gen Surg, Tianjin, Peoples R China		Liu, T (corresponding author), 154 Anshan Rd, Tianjin 300070, Peoples R China.	tongliu12@163.com					Brown JM, 2005, NAT REV CANCER, V5, P231, DOI 10.1038/nrc1560; Glick D, 2010, J PATHOL, V221, P3, DOI 10.1002/path.2697; Gravalos C, 2009, CLIN TRANSL ONCOL, V11, P526, DOI 10.1007/s12094-009-0397-8; Haggar Fatima A, 2009, Clin Colon Rectal Surg, V22, P191, DOI 10.1055/s-0029-1242458; Hasima N, 2014, CELL DEATH DIS, V5, DOI 10.1038/cddis.2014.467; Hu F, 2015, J PHARMACOL SCI, V128, P27, DOI 10.1016/j.jphs.2015.04.003; Indrova M, 2006, INT J ONCOL, V28, P253; Komori S, 2013, MOL CLIN ONCOL, V1, P453, DOI 10.3892/mco.2013.71; Marino G, 2014, NAT REV MOL CELL BIO, V15, P81, DOI 10.1038/nrm3735; Pattingre S, 2005, CELL, V122, P927, DOI 10.1016/j.cell.2005.07.002; Schonewolf CA, 2014, WORLD J GASTRO ONCOL, V6, P74, DOI 10.4251/wjgo.v6.i3.74; Sui X, 2013, CELL DEATH DIS, V4, DOI 10.1038/cddis.2013.350; Suzuki K, 2001, EMBO J, V20, P5971, DOI 10.1093/emboj/20.21.5971; Toden S, 2016, ONCOTARGET, V7, P16158, DOI 10.18632/oncotarget.7567; Trakarnsanga A, 2012, WORLD J GASTROENTERO, V18, P5521, DOI 10.3748/wjg.v18.i39.5521; Tsujimoto Y, 2005, CELL DEATH DIFFER, V12, P1528, DOI 10.1038/sj.cdd.4401777; Wang LJ, 2016, TUMOR BIOL, V37, P11743, DOI 10.1007/s13277-016-5018-x; Zhu GQ, 2015, J NEUROSCI, V35, P621, DOI 10.1523/JNEUROSCI.2193-14.2015; Zhu GQ, 2014, PHYTOTHER RES, V28, P179, DOI 10.1002/ptr.4975; Zhu GQ, 2012, NEUROCHEM INT, V60, P400, DOI 10.1016/j.neuint.2012.01.003; Zilfou JT, 2009, CSH PERSPECT BIOL, V1, DOI 10.1101/cshperspect.a001883	21	10	11	0	5	WOLTERS KLUWER MEDKNOW PUBLICATIONS	MUMBAI	WOLTERS KLUWER INDIA PVT LTD , A-202, 2ND FLR, QUBE, C T S  NO 1498A-2 VILLAGE MAROL, ANDHERI EAST, MUMBAI, 400059, INDIA	0973-1482	1998-4138		J CANCER RES THER	J. Canc. Res. Ther.	DEC	2018	14			5			S1141	S1147		10.4103/0973-1482.204898			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	HE5TR	WOS:000453452300035	30539860	gold			2022-04-25	
J	Kaluderovic, GN; Mijatovic, SA; Zmejkovski, BB; Bulatovic, MZ; Gomez-Ruiz, S; Mojic, MK; Steinborn, D; Miljkovic, DM; Schmidt, H; Stosic-Grujicic, SD; Sabo, TJ; Maksimovic-Ivanic, DD				Kaluderovic, Goran N.; Mijatovic, Sanja A.; Zmejkovski, Bojana B.; Bulatovic, Mirna Z.; Gomez-Ruiz, Santiago; Mojic, Marija K.; Steinborn, Dirk; Miljkovic, Djordje M.; Schmidt, Harry; Stosic-Grujicic, Stanislava D.; Sabo, Tibor J.; Maksimovic-Ivanic, Danijela D.			Platinum(II/IV) complexes containing ethylenediamine-N,N '-di-2/3-propionate ester ligands induced caspase-dependent apoptosis in cisplatin-resistant colon cancer cells	METALLOMICS			English	Article							VITRO ANTITUMORAL ACTIVITY; IN-VITRO; STEREOSPECIFIC LIGANDS; ANTICANCER ACTIVITY; MECHANISMS; CRYSTAL; INHIBITOR; COMPOUND; TOXICITY; TARGET	Several new R(2)eddp (R = i-Pr, i-Bu; eddp = ethylenediamine-N,N'-di-3-propionate) esters and corresponding platinum(II) and platinum(IV) complexes of the general formula [PtCln(R(2)edda-type)] (n = 2, 4) were synthesized and characterized by spectroscopic methods (IR, H-1 and C-13 NMR) and elemental analysis. The crystal structure of platinum(IV) complex [PtCl4{(c-Pe)(2)eddip}] (3a) was resolved and is given herein. Ligand precursors, platinum(II), and platinum(IV) complexes were tested against eight tumor cell lines (CT26CL25, HTC116, SW620, PC3, LNCaP, U251, A375, and B16). Selectivity in the action of those compounds between tumor and two normal primary cells (fibroblasts and keratinocytes) are discussed. A structure-activity relationship of these compounds is discussed. Furthermore, cell cycle distribution, induction of necrosis, apoptosis, autophagy, anoikis, caspase activation, ROS, and RNS are presented on the cisplatin-resistant colon carcinoma HCT116 cell line.	[Kaluderovic, Goran N.; Zmejkovski, Bojana B.; Steinborn, Dirk; Schmidt, Harry] Univ Halle Wittenberg, Inst Chem, D-06120 Halle, Germany; [Mijatovic, Sanja A.; Bulatovic, Mirna Z.; Mojic, Marija K.; Miljkovic, Djordje M.; Stosic-Grujicic, Stanislava D.; Maksimovic-Ivanic, Danijela D.] Univ Belgrade, Inst Biol Res Sinisa Stankovic, Belgrade 11060, Serbia; [Zmejkovski, Bojana B.] Univ Belgrade, Inst Chem Technol & Met, Dept Chem, Belgrade 11000, Serbia; [Gomez-Ruiz, Santiago] Univ Rey Juan Carlos, ESCET, Dept Quim Inorgan & Analit, Madrid 28933, Spain; [Sabo, Tibor J.] Univ Belgrade, Fac Chem, Belgrade 11000, Serbia		Kaluderovic, GN (corresponding author), Univ Halle Wittenberg, Inst Chem, Kurt Mothes Str 2, D-06120 Halle, Germany.	goran.kaluderovic@chemie.uni-halle.de; nelamax@yahoo.com	Mojić, Marija/E-8729-2015; Miljković, Đorđe/F-1378-2015; Gómez-Ruiz, Santiago/E-4863-2012; Kaluderovic, Goran/AAR-7347-2021; Sabo, Tibor/Q-6063-2016; Kaluđerović, Goran/E-6310-2013; Stosic-Grujicic, Stanislava/E-6828-2015; Maksimović-Ivanić, Danijela/E-7246-2015; Bulatović, Mirna/L-6826-2015; Mijatović, Sanja/E-7662-2015	Mojić, Marija/0000-0002-4906-9880; Miljković, Đorđe/0000-0002-5613-9306; Gómez-Ruiz, Santiago/0000-0001-9538-8359; Kaluderovic, Goran/0000-0001-5168-1000; Sabo, Tibor/0000-0002-9866-327X; Kaluđerović, Goran/0000-0001-5168-1000; Stosic-Grujicic, Stanislava/0000-0002-9845-3299; Maksimović-Ivanić, Danijela/0000-0002-8006-5079; Bulatović, Mirna/0000-0002-5472-6144; Mijatović, Sanja/0000-0001-9509-9098	Alexander von Humboldt FoundationAlexander von Humboldt Foundation; Ministry of Science and Technological Development of the Republic of SerbiaMinistry of Education, Science & Technological Development, Serbia [172035, 173013]	GNK acknowledges financial support from the Alexander von Humboldt Foundation. The authors are grateful to the Ministry of Science and Technological Development of the Republic of Serbia for financial support (Grant Nos. 172035 and 173013). We would also like to thank Mrs Heidrun Felgner for language corrections of the manuscript.	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J	Chiacchiera, F; Simone, C				Chiacchiera, Fulvio; Simone, Cristiano			The AMPK-FoxO3A axis as a target for cancer treatment	CELL CYCLE			English	Review						AMPK; FoxO3A; cancer; signal-dependent transcription; antitumor therapy; cell metabolism; calorie restriction	FOXO TRANSCRIPTION FACTORS; ACTIVATED PROTEIN-KINASE; PEUTZ-JEGHERS-SYNDROME; LIFE-SPAN; GENE-EXPRESSION; PROMOTES TUMORIGENESIS; DEPENDENT REGULATION; CALORIC RESTRICTION; CELL-PROLIFERATION; LKB1-AMPK PATHWAY	FoxO proteins are an evolutionarily conserved subfamily of transcription factors involved in tumor suppression, regulation of energy metabolism and development in several tissues, and are mainly regulated by phosphorylation-dependent nuclear/cytoplasmic shuttling. The transcriptional activity of FoxO3A, one of the four members of the family, is further modulated by AMPK, one of the key regulators of cellular metabolism, which basically shifts cell machinery from energy-consuming to energy-producing pathways. We recently demonstrated that the AMPK/FoxO3A energy sensor pathway is still inducible in human cancer cells in response to metabolic stress, as it becomes activated in colorectal and ovarian cancer cells in response to the inhibition of p38 alpha. Activation of the FoxO3A transcriptional program initially induces autophagy as an attempt to retain energy to survive, whereas under persistent stress conditions it triggers autophagic cell death. In this review, we focus on the connections between AMPK and FoxO3A, describing their central role as modulators of fundamental processes such as stress resistance, cell metabolism, autophagy and cell death, and highlighting the therapeutic potential of pharmacological modulation of the AMPK-FoxO3A axis.	[Chiacchiera, Fulvio; Simone, Cristiano] Consorzio Mario Negri Sud, Lab Signal Dependent Transcript, DTP, Chieti, Italy		Simone, C (corresponding author), Consorzio Mario Negri Sud, Lab Signal Dependent Transcript, DTP, Chieti, Italy.	simone@negrisud.it	Chiacchiera, Fulvio/K-6740-2016; Chiacchiera, Fulvio/ABD-6137-2020; SIMONE, Cristiano/K-3452-2018	Chiacchiera, Fulvio/0000-0003-3830-2090; SIMONE, Cristiano/0000-0002-2628-7658	FIRC (Italian Foundation for Cancer Research)Fondazione AIRC per la ricerca sul cancro; Italian Association for Cancer Research (AIRC)Fondazione AIRC per la ricerca sul cancro	We thank Dr. Francesco Paolo Jori for his helpful discussion during the preparation of the manuscript and editorial assistance. Dr. Chiacchiera is supported by FIRC (Italian Foundation for Cancer Research) fellowships. This work was partially supported by a 'My First Grant' from the Italian Association for Cancer Research (AIRC).	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J	Qiu, SL; Xiao, ZC; Piao, CM; Xian, YL; Jia, LX; Qi, YF; Han, JH; Zhang, YY; Du, J				Qiu, Shu-Lan; Xiao, Zhi-Cheng; Piao, Chun-Mei; Xian, Ying-Lin; Jia, Li-Xin; Qi, Yong-Fen; Han, Jia-Huai; Zhang, You-yi; Du, Jie			AMP-activated Protein Kinase alpha 2 Protects against Liver Injury from Metastasized Tumors via Reduced Glucose Deprivation-induced Oxidative Stress	JOURNAL OF BIOLOGICAL CHEMISTRY			English	Article						AMP-activated kinase (AMPK); Glucose; Metastasis; Oxidative Stress; Tumor	REACTIVE OXYGEN; CELL-DEATH; TNF-ALPHA; ENERGY; MITOCHONDRIA; AUTOPHAGY; CANCER; PHOSPHORYLATION; STARVATION; APOPTOSIS	Background: AMPK senses energetic changes and regulates glucose metabolism. Results: AMPK 2 deficiency aggravated the glucose deprivation and necrosis of the hepatocytes via increased ROS production and decreased mitophagy. Conclusion: AMPK 2 is essential for attenuation of liver injury during tumor metastasis. Significance: This is the first time to reveal the mechanism by which glucose/energy competition induced tissue damage in tumor. It is well known that tumors damage affected tissues; however, the specific mechanism underlying such damage remains elusive. AMP-activated protein kinase (AMPK) senses energetic changes and regulates glucose metabolism. In this study, we examined the mechanisms by which AMPK promotes metabolic adaptation in the tumor-bearing liver using a murine model of colon cancer liver metastasis. Knock-out of AMPK 2 significantly enhanced tumor-induced glucose deprivation in the liver and increased the extent of liver injury and hepatocyte death. Mechanistically, we observed that AMPK 2 deficiency resulted in elevated reactive oxygen species, reduced mitophagy, and increased cell death in response to tumors or glucose deprivation in vitro. These results imply that AMPK 2 is essential for attenuation of liver injury during tumor metastasis via hepatic glucose deprivation and mitophagy-mediated inhibition of reactive oxygen species production. Therefore, AMPK 2 might represent an important therapeutic target for colon cancer metastasis-induced liver injury.	[Qiu, Shu-Lan; Xiao, Zhi-Cheng; Piao, Chun-Mei; Xian, Ying-Lin; Jia, Li-Xin; Du, Jie] Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Minist Educ,Key Lab Remodeling Related Cardiovasc, Beijing 100029, Peoples R China; [Qi, Yong-Fen; Zhang, You-yi] Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Lab Cardiovasc Bioact Mol, Beijing 100191, Peoples R China; [Han, Jia-Huai] Xiamen Univ, Sch Biol Sci, Xiamen 361005, Peoples R China		Du, J (corresponding author), Capital Med Univ, Inst Heart Lung & Blood Vessel Dis, Beijing Anzhen Hosp, Beijing 100029, Peoples R China.	jdu@bcm.edu	Han, J/G-4671-2010		Chinese Ministry of Science and TechnologyMinistry of Science and Technology, China [2009CB522205, 2012AA02A201]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81230006, 31090363, 81000871]	This work was supported by Chinese Ministry of Science and Technology Grants 2009CB522205 and 2012AA02A201 and National Natural Science Foundation of China Grants 81230006, 31090363, and 81000871.	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Biol. Chem.	MAR 28	2014	289	13					9449	9459		10.1074/jbc.M113.543447			11	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	AD7UJ	WOS:000333472100060	24515110	Green Published, hybrid			2022-04-25	
J	Che, N; Yang, ZT; Liu, XZ; Li, MX; Feng, Y; Zhang, CY; Li, C; Cui, Y; Xuan, YH				Che, Nan; Yang, Zhaoting; Liu, Xingzhe; Li, Mengxuan; Feng, Ying; Zhang, Chengye; Li, Chao; Cui, Yan; Xuan, Yanhua			Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species-induced autophagy	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE			English	Article						autophagy; colorectal cancer; LETM1; reactive oxygen species	NEGATIVE BREAST-CANCER; ROS; APOPTOSIS; INVASION; DAMAGE	Leucine zipper-EF-hand-containing transmembrane protein 1 (LETM1) is a mitochondrial inner membrane protein that is highly expressed in various cancers. Although LETM1 is known to be associated with poor prognosis in colorectal cancer (CRC), its roles in autophagic cell death in CRC have not been explored. In this study, we examined the mechanisms through which LETM1 mediates autophagy in CRC. Our results showed that LETM1 was highly expressed in CRC tissues and that down-regulation of LETM1 inhibited cell proliferation and induced S-phase arrest. LETM1 silencing also suppressed cancer stem cell-like properties and induced autophagy in CRC cells. Additionally, the autophagy inhibitor 3-methyladenine reversed the inhibitory effects of LETM1 silencing on proliferation and stemness, whereas the autophagy activator rapamycin had the opposite effects. Mechanistically, suppression of LETM1 increased the levels of reactive oxygen species (ROS) and mitochondrial ROS by regulation of SOD2, which in turn activated AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), initiated autophagy, and inhibited proliferation and stemness. Our findings suggest that silencing LETM1 induced autophagy in CRC cells by triggering ROS-mediated AMPK/mTOR signalling, thus blocking CRC progression, which will enhance our understanding of the molecular mechanism of LETM1 in CRC.	[Che, Nan; Yang, Zhaoting; Liu, Xingzhe; Feng, Ying; Xuan, Yanhua] Yanbian Univ, Dept Pathol, Coll Med, Yanji, Peoples R China; [Che, Nan; Yang, Zhaoting; Liu, Xingzhe; Li, Mengxuan; Feng, Ying; Zhang, Chengye; Li, Chao; Xuan, Yanhua] Yanbian Univ, Inst Regenerat Med, Coll Med, Yanji, Peoples R China; [Cui, Yan] Yanbian Univ, Dept Oncol, Affiliated Hosp, Yanji, Peoples R China		Cui, Y (corresponding author), Yanbian Univ, Dept Oncol, Affiliated Hosp, 1827 Juzi Rd, Yanji 133002, Peoples R China.; Xuan, YH (corresponding author), Yanbian Univ, Dept Pathol, Coll Med, 977 Gongyuan Rd, Yanji 133002, Peoples R China.	13514336939@163.com; xuanyh1@ybu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81760531]	National Natural Science Foundation of China, Grant/Award Number: 81760531	Grinevicius VMAD, 2016, J ETHNOPHARMACOL, V189, P139, DOI 10.1016/j.jep.2016.05.020; Bai J, 2020, WORLD J STEM CELLS, V12, P87, DOI 10.4252/wjsc.v12.i1.87; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Chen L, 2017, ONCOTARGET, V8, P93878, DOI 10.18632/oncotarget.21317; Chi JY, 2020, CELL SIGNAL, V65, DOI 10.1016/j.cellsig.2019.109419; Doonan PJ, 2014, FASEB J, V28, P4936, DOI 10.1096/fj.14-256453; Fulda S, 2015, ONCOGENE, V34, P5105, DOI 10.1038/onc.2014.458; Garcia-Aranda M, 2019, CANCERS, V11, DOI 10.3390/cancers11040433; Hamurcu Z, 2018, J CANCER RES CLIN, V144, P415, DOI 10.1007/s00432-017-2557-5; Han KH, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20215300; Huang BS, 2017, ONCOL REP, V38, P2935, DOI 10.3892/or.2017.5959; Huang E, 2017, NAT COMMUN, V8, DOI 10.1038/s41467-017-01435-1; Iachettini S, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-1065-0; Jiang DW, 2013, P NATL ACAD SCI USA, V110, pE2249, DOI 10.1073/pnas.1308558110; Jiang DW, 2009, SCIENCE, V326, P144, DOI 10.1126/science.1175145; Kozovska Z, 2014, BIOMED PHARMACOTHER, V68, P911, DOI 10.1016/j.biopha.2014.10.019; Levy JMM, 2017, NAT REV CANCER, V17, P528, DOI 10.1038/nrc.2017.53; Li HY, 2020, EXP MOL PATHOL, V112, DOI 10.1016/j.yexmp.2019.104333; Li LL, 2015, CELL MOL NEUROBIOL, V35, P615, DOI 10.1007/s10571-015-0166-x; Li RW, 2017, FOOD CHEM TOXICOL, V100, P183, DOI 10.1016/j.fct.2016.12.029; Lin JZ, 2020, CANCER LETT, V469, P481, DOI 10.1016/j.canlet.2019.11.014; Lin ZF, 2013, BIOCHEM BIOPH RES CO, V441, P191, DOI 10.1016/j.bbrc.2013.10.033; Liu JL, 2019, AGING-US, V11, P7830, DOI 10.18632/aging.102291; McQuibban AG, 2010, HUM MOL GENET, V19, P987, DOI 10.1093/hmg/ddp563; Moloney JN, 2018, SEMIN CELL DEV BIOL, V80, P50, DOI 10.1016/j.semcdb.2017.05.023; Piao LH, 2019, PATHOL RES PRACT, V215, DOI 10.1016/j.prp.2019.152437; Piao LZ, 2019, BMC CANCER, V19, DOI 10.1186/s12885-019-6128-9; Piao LZ, 2009, CELL SIGNAL, V21, P767, DOI 10.1016/j.cellsig.2009.01.020; Son YW, 2019, FREE RADICAL BIO MED, V134, P260, DOI 10.1016/j.freeradbiomed.2019.01.001; Tang ZH, 2017, REDOX BIOL, V12, P367, DOI 10.1016/j.redox.2017.03.009; Teng JF, 2019, PHARMACOL RES, V147, DOI 10.1016/j.phrs.2019.104396; Vincent A, 2019, WORLD J STEM CELLS, V11, P920, DOI 10.4252/wjsc.v11.i11.920; Wang K, 2019, TRENDS BIOCHEM SCI, V44, P401, DOI 10.1016/j.tibs.2019.01.001; [王贞 Wang Zhen], 2019, [振动与冲击, Journal of Vibration and Shock], V38, P1; Wen CY, 2019, CELL DEATH DIS, V10, DOI 10.1038/s41419-019-2035-x; Yan JH, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-019-1355-0; Yang ZT, 2018, EXP CELL RES, V373, P145, DOI 10.1016/j.yexcr.2018.10.006; Yang ZT, 2018, HUM PATHOL, V81, P148, DOI 10.1016/j.humpath.2018.07.001; Zarcos-Pedrinaci I, 2018, CANCER RES TREAT, V50, P1270, DOI 10.4143/crt.2017.371; Zhang JH, 2017, J AGR FOOD CHEM, V65, P8966, DOI 10.1021/acs.jafc.7b03822; Zhang JX, 2017, EXP GERONTOL, V89, P45, DOI 10.1016/j.exger.2017.01.010; Zhou J, 2019, THERANOSTICS, V9, P5577, DOI 10.7150/thno.34663	42	4	4	3	5	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1582-1838	1582-4934		J CELL MOL MED	J. Cell. Mol. Med.	FEB	2021	25	4					2110	2120		10.1111/jcmm.16169		DEC 2020	11	Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Research & Experimental Medicine	QG9KQ	WOS:000598053800001	33314691	gold, Green Published			2022-04-25	
J	Schutz, CA; Staedler, D; Crosbie-Staunton, K; Movia, D; Bernasconi, CC; Kenzaoui, BH; Prina-Mello, A; Juillerat-Jeanneret, L				Schuetz, Catherine A.; Staedler, Davide; Crosbie-Staunton, Kieran; Movia, Dania; Bernasconi, Catherine Chapuis; Kenzaoui, Blanka Halamoda; Prina-Mello, Adriele; Juillerat-Jeanneret, Lucienne			Differential stress reaction of human colon cells to oleic-acid-stabilized and unstabilized ultrasmall iron oxide nanoparticles	INTERNATIONAL JOURNAL OF NANOMEDICINE			English	Article						oleic acid; ultrasmall iron oxide nanoparticles; human colon cells; lipid vacuoles; stress reaction; heat shock proteins	SUPERPARAMAGNETIC NANOPARTICLES; SURFACE-CHEMISTRY; OXIDATIVE STRESS; DELIVERY VECTORS; CONTRAST AGENTS; CANCER-CELLS; CYTOTOXICITY; GENOTOXICITY; INHIBITION; METABOLISM	Therapeutic engineered nanoparticles (NPs), including ultrasmall superparamagnetic iron oxide (USPIO) NPs, may accumulate in the lower digestive tract following ingestion or injection. In order to evaluate the reaction of human colon cells to USPIO NPs, the effects of non-stabilized USPIO NPs (NS-USPIO NPs), oleic-acid-stabilized USPIO NPs (OA-USPIO NPs), and free oleic acid (OA) were compared in human HT29 and CaCo2 colon epithelial cancer cells. First the biophysical characteristics of NS-USPIO NPs and OA-USPIO NPs in water, in cell culture medium supplemented with fetal calf serum, and in cell culture medium preconditioned by HT29 and CaCo2 cells were determined. Then, stress responses of the cells were evaluated following exposure to NS-USPIO NPs, OA-USPIO NPs, and free OA. No modification of the cytoskeletal actin network was observed. Cell response to stress, including markers of apoptosis and DNA repair, oxidative stress and degradative/autophagic stress, induction of heat shock protein, or lipid metabolism was determined in cells exposed to the two NPs. Induction of an autophagic response was observed in the two cell lines for both NPs but not free OA, while the other stress responses were cell-and NP-specific. The formation of lipid vacuoles/droplets was demonstrated in HT29 and CaCo2 cells exposed to OA-USPIO NPs but not to NS-USPIO NPs, and to a much lower level in cells exposed to equimolar concentrations of free OA. Therefore, the induction of lipid vacuoles in colon cells exposed to OA utilized as a stabilizer for USPIO NPs is higly amplified compared to free OA, and is not observed in the absence of this lipid in NS-USPIO NPs.	[Schuetz, Catherine A.; Bernasconi, Catherine Chapuis; Kenzaoui, Blanka Halamoda; Prina-Mello, Adriele; Juillerat-Jeanneret, Lucienne] CHU Vaudois, UNIL, CH-1015 Lausanne, Switzerland; [Staedler, Davide] Ecole Polytech Fed Lausanne, Inst Chem Sci & Engn, CH-1015 Lausanne, Switzerland; [Crosbie-Staunton, Kieran; Prina-Mello, Adriele] Trinity Coll Dublin, Sch Med, Dublin, Ireland; [Movia, Dania; Prina-Mello, Adriele] Trinity Coll Dublin, CRANN, Dublin, Ireland		Juillerat-Jeanneret, L (corresponding author), Univ Inst Pathol, Rue Bugnon 25, CH-1011 Lausanne, Switzerland.	prinamea@tcd.ie; lucienne.juillerat@chuv.ch	Movia, Dania/T-6552-2018; Prina-Mello, Adriele/C-6458-2011	Movia, Dania/0000-0001-6412-8132; Prina-Mello, Adriele/0000-0002-4371-2214	European CommissionEuropean CommissionEuropean Commission Joint Research Centre [NMP4-CA-2008-21853, HEALTH-2007-201335, NMP4-LA-2010-246479, NMP4-LA-2011-262943, NMP6-LA-2013-310584]	The authors want to thank the TCD CRANN Advanced Microscopy Laboratory, and in particular Dr Valerie Gerard, for the preparation of the TEM images of the received NPs and Seher Guney-Ayra for technical assistance. This work was partially supported by the European Commission 7th Framework Projects NanoImpactNet (NMP4-CA-2008-21853), NanoTEST (HEALTH-2007-201335), NAM-DIATREAM (NMP4-LA-2010-246479), MULTIFUN (NMP4-LA-2011-262943), and NANoREG (NMP6-LA-2013-310584).	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J. Nanomed.		2014	9						3481	3498		10.2147/IJN.S65082			18	Nanoscience & Nanotechnology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics; Pharmacology & Pharmacy	AM4UR	WOS:000339851900001	25092978	Green Published, gold, Green Submitted			2022-04-25	
J	Lu, CM; Chen, JF; Xu, HG; Zhou, XZ; He, QQ; Li, YL; Jiang, GQ; Shan, YX; Xue, BX; Zhao, RX; Wang, Y; Werle, KD; Cui, RT; Liang, JY; Xu, ZX				Lu, Changming; Chen, Jianfeng; Xu, Hua-Guo; Zhou, Xianzheng; He, Qiongqiong; Li, Yu-Lin; Jiang, Guoqing; Shan, Yuxi; Xue, Boxin; Zhao, Rui-Xun; Wang, Yong; Werle, Kaitlin D.; Cui, Rutao; Liang, Jiyong; Xu, Zhi-Xiang			MIR106B and MIR93 Prevent Removal of Bacteria From Epithelial Cells by Disrupting ATG16L1-Mediated Autophagy	GASTROENTEROLOGY			English	Article						Inflammatory Bowel Disease; microRNA; Cell Biology; Infection	INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; C-MYC; ANTIGEN PRESENTATION; SUSCEPTIBILITY LOCI; MAMMALIAN AUTOPHAGY; IMPAIRED AUTOPHAGY; EXPRESSION; ATG16L1	BACKGROUND & AIMS: Variants in genes that regulate autophagy have been associated with Crohn's disease (CD). Defects in autophagy-mediated removal of pathogenic microbes could contribute to the pathogenesis of CD. We investigated the role of the microRNAs (miRs) MIR106B and MIR93 in induction of autophagy and bacterial clearance in human cell lines and the correlation between MIR106B and autophagy-related gene 16L1 (ATG16L1) expression in tissues from patients with CD. METHODS: We studied the ability of MIR106B and MIR93 to regulate ATG transcripts in human cancer cell lines (HCT116, SW480, HeLa, and U2OS) using luciferase report assays and bioinformatics analyses; MIR106B and MIR93 mimics and antagonists were transfected into cells to modify levels of miRs. Cells were infected with LF82, a CD-associated adherent-invasive strain of Escherichia coli, and monitored by confocal microscopy and for colony-forming units. Colon tissues from 41 healthy subjects (controls), 22 patients with active CD, 16 patients with inactive CD, and 7 patients with chronic inflammation were assessed for levels of MIR106B and ATG16L1 by in situ hybridization and immunohistochemistry. RESULTS: Silencing Dicer1, an essential processor of miRs, increased levels of ATG protein and formation of autophagosomes in cells, indicating that miRs regulate autophagy. Luciferase reporter assays indicated that MIR106B and MIR93 targeted ATG16L1 messenger RNA. MIR106B and MIR93 reduced levels of ATG16L1 and autophagy; these increased after expression of ectopic ATG16L1. In contrast, MIR106B and MIR93 antagonists increased formation of autophagosomes. Levels of MIR106B were increased in intestinal epithelia from patients with active CD, whereas levels of ATG16L1 were reduced compared with controls. Levels of c-Myc were also increased in intestinal epithelia of patients with active CD compared with controls. These alterations could impair removal of CD-associated bacteria by autophagy. CONCLUSIONS: In human cell lines, MIR106B and MIR93 reduce levels of ATG16L1 and autophagy and prevent autophagy-dependent eradication of intracellular bacteria. This process also appears to be altered in colon tissues from patients with active CD.	[Lu, Changming; Chen, Jianfeng; Xu, Hua-Guo; Zhao, Rui-Xun; Wang, Yong; Werle, Kaitlin D.; Xu, Zhi-Xiang] Univ Alabama Birmingham, Ctr Comprehens Canc, Div Hematol & Oncol, Birmingham, AL 35205 USA; [Zhou, Xianzheng] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA; [Zhou, Xianzheng] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA; [Zhou, Xianzheng] New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA; [Zhou, Xianzheng] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA; [He, Qiongqiong] Cent S Univ, Xiangya Sch Med, Dept Pathol, Changsha, Hunan, Peoples R China; [Li, Yu-Lin] Jilin Univ, Norman Bethune Coll Med, Minist Educ, Key Lab Pathobiol, Changchun 130023, Jilin, Peoples R China; [Jiang, Guoqing; Shan, Yuxi; Xue, Boxin] Soochow Univ, Affiliated Hosp 2, Dept Surg, Suzhou, Jiangsu, Peoples R China; [Cui, Rutao] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA; [Liang, Jiyong] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA		Xu, ZX (corresponding author), Univ Alabama Birmingham, Ctr Comprehens Canc, Div Hematol & Oncol, Wallace Tumor Inst Bldg,Room 520D,1824 6th Ave So, Birmingham, AL 35205 USA.	zhixiangxu@uabmc.edu			National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA133053, P50CA098252]; National Institute of Allergy and Infectious DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R21AI092220]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA016672, R01CA133053, P50CA098252] Funding Source: NIH RePORTER; NATIONAL CENTER FOR RESEARCH RESOURCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [P20RR021905] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R21AI092220] Funding Source: NIH RePORTER	Supported by National Cancer Institute grant R01CA133053, the National Cancer Institute Cervical Cancer SPORE Career Development Award and Pilot Award P50CA098252 (to Z.-X.X.), and National Institute of Allergy and Infectious Diseases grant R21AI092220 (to X.Z.).	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J	Lee, JJ; Park, IH; Rhee, WJ; Kim, HS; Shin, JS				Lee, Je-Jung; Park, In Ho; Rhee, Woo Joong; Kim, Hee Sue; Shin, Jeon-Soo			HMGB1 modulates the balance between senescence and apoptosis in response to genotoxic stress	FASEB JOURNAL			English	Article						cancer; metastasis; cell fate; doxorubicin; camptothecin	CELLULAR SENESCENCE; SECRETORY PHENOTYPE; CANCER CELLS; PROTEIN; TUMORIGENESIS; SUPPRESSION; AUTOPHAGY; RELEASE; COMPLEX; P53	High mobility group box-1 (HMGB1) is involved in various diseases and is associated with the resistance of many types of human cancers to chemotherapy; however, its role in cancer metastasis remains unexplored. This study examined the HMGB1 status of both highly and poorly metastatic cancer cells in response to genotoxic stress. The weakly and highly metastatic mouse melanoma cell lines (B16 vs. B16-F10), human melanoma cell lines (SK-MEL-28 vs. SK-MEL-24), colon cancer cell lines (DLD-1 vs. LS174T), and wild-type (WT) vs. HMGB1 knockout (KO) mouse embryonic fibroblasts (MEFs) were treated with doxorubicin (Dox) and camptothecin (CPT), and then cellular morphology, senescence-associated beta-galactosidase staining, lactate dehydrogenase release, and caspase-3 activation were used to assess cell fate. To investigate the role of HMGB1 in p21 expression, HMGB1 and p21 expressions were examined by Western blotting, and the HMGB1-mediated p21 promoter luciferase assay was performed after small interfering RNA or overexpression of HMGB1 prior to Dox treatment. Although highly metastatic mouse melanoma B16-F10 cells preferred senescence, with persistent HMGB1 expression, poorly metastatic B16 cells entered apoptosis, with decreasing HMGB1 levels via cleavage under Dox treatment. Similarly, more metastatic human melanoma SK-MEL-24 and human colon cancer LS174T cells underwent senescence, whereas fewer metastatic melanoma SK-MEL-28 and DLD-1 cells exhibited apoptosis under Dox stimulation. In senescent B16-F10, SK-MEL-24, and LS174T cells treated with Dox, p21 levels were increased by persistent HMGB1 expression. Furthermore, HMGB1 depletion caused a senescence-apoptosis shift with p21 down-regulation in B16-F10 cells, and HMGB1 overexpression switched from apoptosis to senescence concomitantly with increased p21 expression in B16 cells after Dox treatment. The same effects were observed in both cell pairs of mouse melanoma and human colon cancer cells treated with CPT, another genotoxic stressor. Indeed, although WT MEF entered senescence accompanied by p21 increase, HMGB1 KO underwent apoptosis with p21 decrease by Dox treatment. In our cell model system, we demonstrated that highly metastatic cancer cells preferentially enter senescence, whereas apoptosis predominates in weakly metastatic cancer cells under genotoxic stress, which depends on the presence or absence of HMGB1, suggesting that the HMGB1-p21 axis is required for genotoxic stress-induced senescence. These findings suggest that HMGB1 modulation of cancers with different metastatic status could be a strategy for selectively enforcing tumor suppression.-Lee, J.-J., Park, I. H., Rhee, W. J., Kim, H. S., Shin, J.-S. HMGB1 modulates the balance between senescence and apoptosis in response to genotoxic stress.	[Lee, Je-Jung; Rhee, Woo Joong; Kim, Hee Sue; Shin, Jeon-Soo] Yonsei Univ, Coll Med, Dept Microbiol, 50-1 Yonsei Ro, Seoul 03722, South Korea; [Lee, Je-Jung; Park, In Ho; Shin, Jeon-Soo] Yonsei Univ, Coll Med, Inst Immunol & Immunol Dis, Seoul, South Korea; [Park, In Ho; Shin, Jeon-Soo] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul, South Korea; [Rhee, Woo Joong; Shin, Jeon-Soo] Inst for Basic Sci Korea, Ctr Nanomed, Seoul, South Korea		Shin, JS (corresponding author), Yonsei Univ, Coll Med, Dept Microbiol, 50-1 Yonsei Ro, Seoul 03722, South Korea.	jsshin6203@yuhs.ac		Rhee, Woo Joong/0000-0001-9690-0553; Shin, Jeon-Soo/0000-0002-8294-3234; Park, In Ho/0000-0003-2190-5469	National Research Foundation of Korea (NRF) - Korean government [2014R1A4A1008625, 2017R1A2B3006704, 2017R1D1A1B03028551, 2019R1I1A1A01041284, 2019R1A6A1A03032869]; Research Center Program of the Institute for Basic Science (IBS) in Korea [IBS-R026-D1]; Brain Korea 21 PLUS Project for Medical Science	This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean government (2014R1A4A1008625, 2017R1A2B3006704, 2017R1D1A1B03028551, 2019R1I1A1A01041284, and 2019R1A6A1A03032869), the Research Center Program of the Institute for Basic Science (IBS) in Korea (IBS-R026-D1), and the Brain Korea 21 PLUS Project for Medical Science. The authors declare no conflicts of interest.	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OCT	2019	33	10					10942	10953		10.1096/fj.201900288R			12	Biochemistry & Molecular Biology; Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology	JC3GG	WOS:000489166300030	31284735				2022-04-25	
J	Mansilla, S; Llovera, L; Portugal, J				Mansilla, Sylvia; Llovera, Laia; Portugal, Jose			Chemotherapeutic Targeting of Cell Death Pathways	ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY			English	Article						Apoptosis; Autophagy; Chemotherapy; Mitotic catastrophe; Necrosis; Senescence	SMALL-MOLECULE INHIBITORS; SENESCENCE-LIKE PHENOTYPE; COLON-CARCINOMA CELLS; 2 DISTINCT MODES; MITOTIC CATASTROPHE; CANCER-THERAPY; DNA-DAMAGE; TUMOR-CELLS; CHECKPOINT ABROGATION; PROLIFERATION ARREST	Cell death plays an important role in cancer growth and progression, as well as in the efficiency of chemotherapy. Although apoptosis is commonly regarded as the principal mechanism of programmed cell death, it has been increasingly reported that several anti-cancer agents do not only induce apoptosis but other forms of cell death such as necrosis, autophagy and mitotic catastrophe, as well as the state of permanent loss of proliferative capacity known as senescence. A deeper understanding of what we know about chemotherapy-induced death is rather relevant considering the emerging knowledge of non-apoptotic cell death signaling pathways, and the fact that many tumors have the apoptosis pathway seriously compromised. In this review we examine the effects that various anti-cancer agents have on pathways involved in the different cell death outcomes. Novel and specific anti-cancer agents directed toward members of the cell death signaling pathways are being developed and currently being tested in clinical trials. If we precisely activate or inhibit molecules that mediate the diversity of cell death outcomes, we might succeed in more effective and less toxic chemotherapy.	[Mansilla, Sylvia; Llovera, Laia; Portugal, Jose] CSIC, Inst Biol Mol Barcelona, E-08028 Barcelona, Spain		Portugal, J (corresponding author), CSIC, Inst Biol Mol Barcelona, Parc Cient Barcelona,Baldiri Reixac 10, E-08028 Barcelona, Spain.	jpmbmc@ibmb.csic.es	Portugal, José/K-4504-2014	Portugal, José/0000-0002-1923-9666; Llovera Nadal, Laia/0000-0002-5836-593X; Mansilla, Sylvia/0000-0003-0181-1721	Spanish Ministry of Science and InnovationSpanish Government [BFU2010-15518]; European CommunityEuropean Commission	This work was supported by grant BFU2010-15518 from the Spanish Ministry of Science and Innovation, and the FEDER program of the European Community, and it was performed within the framework of the Xarxa de Referencia en Biotecnologia of the Generalitat de Catalunya. We apologize to authors whose work has not been included.	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Chem.	MAR	2012	12	3					226	238		10.2174/187152012800228805			13	Oncology; Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	936TR	WOS:000303613400009	22263795				2022-04-25	
J	Hrabakova, R; Kollareddy, M; Tyleckova, J; Halada, P; Hajduch, M; Gadher, SJ; Kovarova, H				Hrabakova, Rita; Kollareddy, Madhu; Tyleckova, Jirina; Halada, Petr; Hajduch, Marian; Gadher, Suresh Jivan; Kovarova, Hana			Cancer Cell Resistance to Aurora Kinase Inhibitors: Identification of Novel Targets for Cancer Therapy	JOURNAL OF PROTEOME RESEARCH			English	Article						Aurora kinase inhibitors; resistance; p5.3; apoptosis; autophagy; platelet-activating factor acetylhydrolase; Ran; serine hydroxymethyltransferase; serpin BS; calretinin	DRUG-RESISTANCE; BREAST-CANCER; P53; CHEMOTHERAPY; EXPRESSION; CHEMORESISTANCE; CARCINOMA; PATHWAY; ACTIVATION; PROTEOMICS	Drug resistance is the major obstacle to successful cancer therapy. Our study focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in clinical trials. We have used 2D electrophoresis in the pH ranges of 4-7 and 6-11 followed by protein identification using MALDI-TOF/TOF to compare the protein composition of HCT116 inhibitors or resistant toward these drugs. The analysis also colon cancer cells either sensitive to CYC116 and ZM447439 included p53(+/+) and p53(-/-) phenotypes of HCT116 cells. Our findings demonstrate that platelet-activating factor acetylhydrolase and GTP-binding nuclear protein Ran contribute to the development of resistance to ZM447439 only where resistance is related to p53. On the other hand, serine hydroxymethyltransferase was found to promote the tumor growth in cells resistant to CYC116 without the influence of p53. Computer modeling of interaction networks highlighted a direct link of the p53-independent mechanism of resistance to CYC116 with autophagy. Importantly, serine hydroxymethyltransferase, serpin B5, and calretinin represent the target proteins that may help overcome resistance in combination therapies. In addition, serpin B5 and calretinin appear to be candidate biomarkers that may be accessible in patients for monitoring of cancer therapy with ease.	[Hrabakova, Rita; Tyleckova, Jirina; Kovarova, Hana] AS CR, Vvi, Inst Anim Physiol & Genet, Lab Biochem & Mol Biol Germ Cells, Libechov 27721, Czech Republic; [Kollareddy, Madhu; Hajduch, Marian] Palacky Univ, Inst Mol & Translat Med, Expt Med Lab, Olomouc 77515, Czech Republic; [Kollareddy, Madhu; Hajduch, Marian] Univ Hosp, Fac Med & Dent, Olomouc 77515, Czech Republic; [Halada, Petr] AS CR, Vvi, Inst Microbiol, Lab Mol Struct Characterisat, Prague 14220, Czech Republic; [Gadher, Suresh Jivan] Life Technol, Frederick, MD 21704 USA		Kovarova, H (corresponding author), AS CR, Vvi, Inst Anim Physiol & Genet, Lab Biochem & Mol Biol Germ Cells, Rumburska 89, Libechov 27721, Czech Republic.	kovarova@iapg.cas.cz	Hajduch, Marian/J-4015-2014; Sucha, Rita/ABA-9387-2021; Kovarova, Hana/G-7135-2014; Hrabakova, Rita/G-7136-2014; Halada, Petr/H-3330-2014; Dzubak, Petr/D-2175-2013	Hajduch, Marian/0000-0002-4834-908X; Sucha, Rita/0000-0002-2808-4870; Halada, Petr/0000-0002-7229-3450; Kollareddy, Madhu/0000-0001-7412-096X; Dzubak, Petr/0000-0002-3098-5969	Ministry of Education, Youth and SportsMinistry of Education, Youth & Sports - Czech Republic [LC07017]; Operational Program Research and Development for InnovationsEuropean Commission [CZ.1.05/2.1.00/01.0030];  [RVO67985904];  [RVO61388971]	We greatly acknowledge Jaroslava Supolikova for skillful technical assistance. This work was supported in part by the Ministry of Education, Youth and Sports (Grant LC07017) and by Institutional Research Projects RVO67985904 (IAPG, AS CR, v.v.i.) and RVO61388971 (IMIC, AS CR, v.v.i.). An infrastructural part of this project was supported from the Operational Program Research and Development for Innovations (CZ.1.05/2.1.00/01.0030).	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Proteome Res.	JAN	2013	12	1					455	469		10.1021/pr300819m			15	Biochemical Research Methods	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	065NX	WOS:000313156300046	23151231				2022-04-25	
J	Aredia, F; Scovassi, AI				Aredia, Francesca; Scovassi, Anna Ivana			A new function for miRNAs as regulators of autophagy	FUTURE MEDICINAL CHEMISTRY			English	Review						antagomir; autophagy; biomarker; cancer; miRNA; oncomiR; tumor suppressor miRNA	CANCER STEM-CELLS; TUMOR SUPPRESSIVE ROLES; COLORECTAL-CANCER; HEPATOCELLULAR-CARCINOMA; DOWN-REGULATION; CIRCULATING MICRORNAS; PROMOTES AUTOPHAGY; SIGNALING NETWORKS; HUMAN GLIOBLASTOMA; SMALL MOLECULES	Autophagy is a self-digestive process regulated by an intricate network of factors able either to ensure the prosurvival function of autophagy or to convert it in a death pathway. Recently, the involvement of miRNAs in the regulation of autophagy networks has been reported. This review will summarize the main features of these small noncoding endogenous RNAs, focusing on their relevance in cancer and finally addressing their impact on autophagy.	[Aredia, Francesca; Scovassi, Anna Ivana] CNR, Ist Genet Mol, Via Abbiategrasso 207, I-27100 Pavia, Italy		Scovassi, AI (corresponding author), CNR, Ist Genet Mol, Via Abbiategrasso 207, I-27100 Pavia, Italy.	scovassi@igm.cnr.it					Abba ML, 2016, J CLIN MED, V5, DOI 10.3390/jcm5010008; Ambros V, 2004, NATURE, V431, P350, DOI 10.1038/nature02871; Ananta JS, 2016, MOL PHARMACEUT, V13, P3164, DOI 10.1021/acs.molpharmaceut.6b00388; Nieto MA, 2013, SCIENCE, V342, P708, DOI 10.1126/science.1234850; Ardekani Ali M., 2010, Avicenna Journal of Medical Biotechnology, V2, P161; Aredia F, 2013, FUTURE MED CHEM, V5, P1009, DOI 10.4155/fmc.13.85; Babashah S, 2011, EUR J CANCER, V47, P1127, DOI 10.1016/j.ejca.2011.02.008; Banwait JK, 2015, ADV DRUG DELIVER REV, V81, P94, DOI 10.1016/j.addr.2014.10.030; Barbagallo D, 2016, ONCOTARGET, V7, P4746, DOI 10.18632/oncotarget.6621; Basak I, 2016, CELL MOL LIFE SCI, V73, P811, DOI 10.1007/s00018-015-2093-x; Berezikov E, 2005, CELL, V120, P21, DOI 10.1016/j.cell.2004.12.031; 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Chem.	JAN	2017	9	1					25	36		10.4155/fmc-2016-0173			12	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	EH6FM	WOS:000391868200003	27957876				2022-04-25	
J	Chaudhary, P; Ha, E; Vo, TTL; Seo, JH				Chaudhary, Prerna; Ha, Eunyoung; Tam Thuy Lu Vo; Seo, Ji Hae			Diverse roles of arrest defective 1 in cancer development	ARCHIVES OF PHARMACAL RESEARCH			English	Review						ARD1; Acetyltransferase; Acetylation; Tumorigenesis	HEPATOCELLULAR-CARCINOMA; POOR-PROGNOSIS; PROTEIN; ACETYLATION; ARD1; EXPRESSION; CONTRIBUTES; METASTASIS; REGULATOR; APOPTOSIS	Arrest defective 1 is an acetyltransferase that acetylates N-terminal amino acid or internal lysine residues of its target proteins. By acetylating its target proteins, ARD1 plays roles in many cellular activities, including proliferation, differentiation, autophagy, and apoptosis. In recent years, a number of investigations have emerged reporting the dysregulated expression of ARD1 in different types of cancer, including lung, liver, pancreas, breast, prostate, and colon cancer. Furthermore, the expression level of ARD1 in cancer tissues has been correlated with the progression and metastasis of the cancer and the survival of cancer patients. Consequently, mechanistic studies have revealed that ARD1-mediated protein acetylation plays an important role in modulating several cellular events that are important for cancer development, such as cell cycle progression, cell death, and migration. On the basis of this evidence, targeting of ARD1 has been proposed as a promising avenue for the development of novel cancer therapeutics. This review summarizes the biological functions of ARD1 in different types of cancer and provides a deep insight into the biochemical activities of ARD1 during tumor progression.	[Chaudhary, Prerna; Ha, Eunyoung; Tam Thuy Lu Vo; Seo, Ji Hae] Keimyung Univ, Sch Med, Dept Biochem, Daegu 42601, South Korea		Seo, JH (corresponding author), Keimyung Univ, Sch Med, Dept Biochem, Daegu 42601, South Korea.	seojh@kmu.ac.kr			National Research Foundation of KoreaNational Research Foundation of Korea [NRF-2016R1A6A1A03011325, NRF-2016R1D1A1B03935560, NRF-2019R1C1C1005855] Funding Source: Medline		Aksnes H, 2019, MOL CELL, V73, P1097, DOI 10.1016/j.molcel.2019.02.007; Arnesen T, 2006, ONCOGENE, V25, P4350, DOI 10.1038/sj.onc.1209469; Arnesen T, 2008, CURR CANCER DRUG TAR, V8, P545, DOI 10.2174/156800908786241113; Balogh J, 2016, J HEPATOCELL CARCINO, V3, P41, DOI 10.2147/JHC.S61146; Banreti A, 2013, AUTOPHAGY, V9, P819, DOI 10.4161/auto.23908; Chien MH, 2018, CANCER LETT, V433, P86, DOI 10.1016/j.canlet.2018.06.033; DePaolo JS, 2016, ONCOTARGET, V7, P71417, DOI 10.18632/oncotarget.12163; Dorfel MJ, 2015, GENE, V567, P103, DOI 10.1016/j.gene.2015.04.085; Drazic A, 2016, BBA-PROTEINS PROTEOM, V1864, P1372, DOI 10.1016/j.bbapap.2016.06.007; Fu MF, 2003, MOL CELL BIOL, V23, P8563, DOI 10.1128/MCB.23.23.8563-8575.2003; Hua KT, 2011, CANCER CELL, V19, P218, DOI 10.1016/j.ccr.2010.11.010; Ji XY, 2014, P NATL ACAD SCI USA, V111, pE4305, DOI 10.1073/pnas.1412289111; Jiang BH, 2010, AM J PATHOL, V177, P1095, DOI 10.2353/ajpath.2010.091178; Kalvik TV, 2013, ONCOGENE, V32, P269, DOI 10.1038/onc.2012.82; Nguyen KT, 2018, EXP MOL MED, V50, DOI 10.1038/s12276-018-0097-y; Kuhns KJ, 2018, EXP MOL MED, V50, DOI 10.1038/s12276-018-0107-0; Kuo HP, 2010, AM J TRANSL RES, V2, P56; Kuo HP, 2010, SCI SIGNAL, V3, DOI 10.1126/scisignal.2000590; Kuo HP, 2009, BIOCHEM BIOPH RES CO, V389, P156, DOI 10.1016/j.bbrc.2009.08.127; Lavery DN, 2011, J BIOMED BIOTECHNOL, DOI 10.1155/2011/862125; Lee CF, 2010, J CLIN INVEST, V120, P2920, DOI 10.1172/JCI42275; Lee D, 2018, EXP MOL MED, V50, DOI 10.1038/s12276-018-0106-1; Lee EJ, 2018, EXP MOL MED, V50, DOI 10.1038/s12276-018-0103-4; Lee EJ, 2017, ONCOTARGET, V8, P68517, DOI 10.18632/oncotarget.19704; Lee MN, 2018, EXP MOL MED, V50, DOI 10.1038/s12276-018-0105-2; Lim JH, 2006, CANCER RES, V66, P10677, DOI 10.1158/0008-5472.CAN-06-3171; Lonergan Peter E, 2011, J Carcinog, V10, P20, DOI 10.4103/1477-3163.83937; Lozada EM, 2016, ONCOTARGET, V7, P20425, DOI 10.18632/oncotarget.7966; Luczak MW, 2006, FOLIA HISTOCHEM CYTO, V44, P143; Markopoulos AK, 2012, OPEN DENT J, V6, P126, DOI 10.2174/1874210601206010126; Marley AR, 2016, INT J MOL EPIDEMIOL, V7, P105; Merriel SWD, 2018, ADV THER, V35, P1285, DOI 10.1007/s12325-018-0766-1; Moskovitz J, 2001, P NATL ACAD SCI USA, V98, P12920, DOI 10.1073/pnas.231472998; PARK EC, 1992, EMBO J, V11, P2087, DOI 10.1002/j.1460-2075.1992.tb05267.x; Park YH, 2017, INT J ONCOL, V51, P573, DOI 10.3892/ijo.2017.4039; Qian X, 2017, AUTOPHAGY, V13, P1246, DOI 10.1080/15548627.2017.1313945; Ree R, 2018, EXP MOL MED, V50, DOI 10.1038/s12276-018-0116-z; Ren TT, 2008, CANCER LETT, V264, P83, DOI 10.1016/j.canlet.2008.01.028; Seo JH, 2016, NAT COMMUN, V7, DOI 10.1038/ncomms12882; Seo JH, 2010, CANCER RES, V70, P4422, DOI 10.1158/0008-5472.CAN-09-3258; Shang YF, 2002, MOL CELL, V9, P601, DOI 10.1016/S1097-2765(02)00471-9; Shim JH, 2012, DIGEST DIS, V30, P603, DOI 10.1159/000343090; Shin DH, 2009, PLOS ONE, V4, DOI 10.1371/journal.pone.0007451; Shin SH, 2014, CELL DEATH DIS, V5, DOI 10.1038/cddis.2014.456; Shtutman M, 1999, P NATL ACAD SCI USA, V96, P5522, DOI 10.1073/pnas.96.10.5522; Soppa J, 2010, ARCHAEA, V2010, DOI 10.1155/2010/820681; Stove SI, 2018, EUR J HUM GENET, V26, P1294, DOI 10.1038/s41431-018-0136-0; Vo TTL, 2018, EXP MOL MED, V50, DOI 10.1038/s12276-018-0100-7; Vo TTL, 2017, ONCOTARGET, V8, P57216, DOI 10.18632/oncotarget.19332; Wang ZH, 2011, ASIAN PAC J CANCER P, V12, P1973; Wang ZH, 2012, P NATL ACAD SCI USA, V109, P3053, DOI 10.1073/pnas.1113356109; Wu YY, 2018, EXP MOL MED, V50, DOI 10.1038/s12276-018-0098-x; Xu HY, 2012, CARCINOGENESIS, V33, P1193, DOI 10.1093/carcin/bgs144; Xu W, 2014, ONCOGENE, V33, P2279, DOI 10.1038/onc.2013.163; Yamaguchi H, 2005, CURR OPIN CELL BIOL, V17, P559, DOI 10.1016/j.ceb.2005.08.002; Yang HJ, 2016, ONCOTARGET, V7, P2709, DOI 10.18632/oncotarget.6458; Yoon H, 2014, NAT COMMUN, V5, DOI 10.1038/ncomms6176; Yu L, 2018, AUTOPHAGY, V14, P207, DOI 10.1080/15548627.2017.1378838; Yu M, 2009, CANCER INVEST, V27, P978, DOI 10.3109/07357900902769723; Zeng Y, 2016, TUMOR BIOL, V37, P6719, DOI 10.1007/s13277-015-4563-z; Zeng Y, 2014, CARCINOGENESIS, V35, P2244, DOI 10.1093/carcin/bgu132; Zhang Y, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0921-2; Zhou Y, 2015, J MOL ENDOCRINOL, V54, pR15, DOI 10.1530/JME-14-0203	63	7	7	1	2	PHARMACEUTICAL SOC KOREA	SEOUL	1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA	0253-6269	1976-3786		ARCH PHARM RES	Arch. Pharm. Res.	DEC	2019	42	12					1040	1051		10.1007/s12272-019-01195-0			12	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	JW3CI	WOS:000502933000002	31813105				2022-04-25	
J	Fu, YY; Hong, L; Xu, JC; Zhong, GP; Gu, Q; Gu, QQ; Guan, YP; Zheng, XP; Dai, Q; Luo, X; Liu, C; Huang, ZY; Yin, XM; Liu, PQ; Li, M				Fu, Yuanyuan; Hong, Liang; Xu, Jiecheng; Zhong, Guoping; Gu, Qiong; Gu, Qianqian; Guan, Yanping; Zheng, Xueping; Dai, Qi; Luo, Xia; Liu, Cui; Huang, Zhiying; Yin, Xiao-Ming; Liu, Peiqing; Li, Min			Discovery of a small molecule targeting autophagy via ATG4B inhibition and cell death of colorectal cancer cells in vitro and in vivo	AUTOPHAGY			English	Article						Anti-tumor; ATG4B; autophagy; cell death; colorectal cancer; delipidation; FRET assay; xenografts	PROTEIN; DERIVATIVES; MODULATION; ASSAY; LC3	Human Atg4 homologs are cysteine proteases, which play key roles in the macroautophagy/autophagy process by cleaving Atg8 homologs for conjugation to lipid membranes and for deconjugation of Atg8 homologs from membranes. Expression of ATG4B is significantly increased in colorectal cancer cells compared to normal cells, suggesting that ATG4B may be important for cancer biology. Inhibition of ATG4B may reduce the autophagy activity, thereby sensitizing cancer cells to therapeutic agents. Thus, developing specific and potent ATG4B inhibitors for research as well as for potential therapeutic uses is highly needed. In this study, we integrated in silico screening and in vitro assays to discover a potent ATG4B inhibitor, named S130, from a noncommercial library. This chemical binds to ATG4B with strong affinity and specifically suppresses the activity of ATG4B but not other proteases. S130 did not cause the impairment of autophagosome fusion, nor did it result in the dysfunction of lysosomes. Instead, S130 might attenuate the delipidation of LC3-II on the autolysosomes to suppress the recycling of LC3-I, which normally occurs after LC3-II cleavage by ATG4B. Intriguingly, S130 induced cell death, which was accompanied with autophagy stress and could be further exacerbated by nutrient deprivation. Such cytotoxicity could be partially reversed by enhancing ATG4B activity. Finally, we found that S130 was distributed in tumor tissues in vivo and was also effective in arresting the growth of colorectal cancer cells. Thus, this study indicates that ATG4B is a potential anticancer target and S130 might be a novel small-molecule candidate for future cancer therapy.	[Fu, Yuanyuan; Hong, Liang; Xu, Jiecheng; Zhong, Guoping; Gu, Qiong; Gu, Qianqian; Guan, Yanping; Zheng, Xueping; Dai, Qi; Luo, Xia; Liu, Cui; Huang, Zhiying; Liu, Peiqing; Li, Min] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Design & Evaluat, Natl & Local United Engn Lab Druggabil & New Drug, Guangzhou, Guangdong, Peoples R China; [Yin, Xiao-Ming] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA		Liu, PQ; Li, M (corresponding author), Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China.	liupq@mail.sysu.edu.cn; limin65@mail.sysu.edu.cn	管, 宴萍/AAL-5308-2020; gu, qiong/N-1653-2017; Xu, Jun/AAI-7544-2020	Xu, Jun/0000-0002-1075-0337; Liu, Peiqing/0000-0003-4388-2173; Gu, Qiong/0000-0001-6011-3697; li, min/0000-0002-5657-8675; Peiqing, Liu/0000-0002-3378-4863	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31671437]; National Science and Technology Major Project of the Ministry of Science and Technology of China [2018ZX09735010]; Natural Science Foundation of Guangdong Province, ChinaNational Natural Science Foundation of Guangdong Province [2016A030313335]; 111 projectMinistry of Education, China - 111 Project [B16047]; Guangdong Provincial Key Laboratory of Construction Foundation [2017B030314030]	This work was supported in part by the National Natural Science Foundation of China (31671437), the National Science and Technology Major Project of the Ministry of Science and Technology of China (2018ZX09735010), the Natural Science Foundation of Guangdong Province, China (2016A030313335), the 111 project (B16047), and the Guangdong Provincial Key Laboratory of Construction Foundation (2017B030314030).	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J	Yan, T; Seo, Y; Schupp, JE; Zeng, XH; Desai, AB; Kinsella, TJ				Yan, T; Seo, Y; Schupp, JE; Zeng, XH; Desai, AB; Kinsella, TJ			Methoxyamine potentiates iododeoxyuridine-induced radiosensitization by altering cell cycle kinetics and enhancing senescence	MOLECULAR CANCER THERAPEUTICS			English	Article							BASE EXCISION-REPAIR; STRAND-BREAK REPAIR; HALOGENATED PYRIMIDINE; DNA-DAMAGE; TUMOR SUPPRESSION; COLON-CANCER; RADIATION; PATHWAYS; SUBSTITUTION; ENHANCEMENT	We previously reported that methoxyamine (an inhibitor of base excision repair) potentiates iododeoxyuridine (IUdR)induced radiosensitization in human tumor cells. In this study, we investigated the potential mechanisms of this enhanced cell death. Human colorectal carcinoma RKO cells were exposed to IUdR (3 mu mol/L) and/or methoxyamine (3 mmol/L) for 48 hours before ionizing radiation (5 Gy). We found that IUdR/methoxyamine altered cell cycle kinetics and led to an increased G(1) population but a decreased S population before ionizing radiation. Immediately following ionizing radiation (up to 6 hours), IUdR/methoxyamine-pretreated cells showed a stringent Gi-S checkpoint but an insufficient G(2)-M checkpoint, whereas a prolonged G(1) arrest, containing 2CG1 and 4CG1 cells, was found at later time:; up to 72 hours. Levels of cell cycle-specific markers [p21, p27, cyclin A, cyclin B1, and pcdc2(Y15)] and DIVA damage signaling proteins [gamma H2AX, pChk1(S317), and pChk2(T68)] supported these altered cell cycle kinetics. Interestingly, we found that IUdR/methoxyamine pretreatment reduced ionizing radiation-induced apoptosis. Additionally, the extent of cell death through necrosis or autophagy seemed similar in all (IUDR +/- methoxyamine + ionizing radiation) treatment groups. However, a larger population of senescence-activated beta-galactosidase-positive cells was seen in IUdR/methoxyamine/ionizing radiation-treated cells, which was correlated with the increased activation of the senescence factors p53 and pRb. These data indicate that Ili methoxyamine pretreatment enhanced the effects of ionizing radiation by causing a prolonged G(1) cell cycle arrest and by promoting stress-induced premature senescence. Thus, senescence, a novel ionizing radiation induced tumor suppression pathway, may be effectively targeted by IUdR/methoxyamine pretreatment, resulting in an improved therapeutic gain for ionizing radiation.	Univ Hosp Cleveland, Ireland Canc Ctr, Dept Radiat Oncol, Cleveland, OH 44106 USA; Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA		Kinsella, TJ (corresponding author), Univ Hosp Cleveland, Ireland Canc Ctr, Dept Radiat Oncol, LTR 6068,11100 Euclid Ave, Cleveland, OH 44106 USA.	timothy.kinsella@uhhs.com			NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA050595] Funding Source: NIH RePORTER; NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA112963, CA50595] Funding Source: Medline		Ben-Porath I, 2005, INT J BIOCHEM CELL B, V37, P961, DOI 10.1016/j.biocel.2004.10.013; Berry SE, 2003, CANCER RES, V63, P5490; Brown M, 2003, CANCER BIOL THER, V2, P477, DOI 10.4161/cbt.2.5.450; Campisi J, 2005, SCIENCE, V309, P886, DOI 10.1126/science.1116801; Campisi J, 2005, CELL, V120, P513, DOI 10.1016/j.cell.2005.02.003; Chehab NH, 2000, GENE DEV, V14, P278; Chen YH, 2004, DNA REPAIR, V3, P1025, DOI 10.1016/j.dnarep.2004.03.003; Collins I, 2005, CURR OPIN PHARMACOL, V5, P366, DOI 10.1016/j.coph.2005.04.009; FORNACE AJ, 1990, INT J RADIAT ONCOL, V18, P873, DOI 10.1016/0360-3016(90)90410-L; Foster ER, 2005, FEBS J, V272, P3231, DOI 10.1111/j.1742-4658.2005.04741.x; Gozuacik D, 2004, ONCOGENE, V23, P2891, DOI 10.1038/sj.onc.1207521; Herskind C, 2000, EXP GERONTOL, V35, P747, DOI 10.1016/S0531-5565(00)00168-6; Hinz JM, 2005, DNA REPAIR, V4, P782, DOI 10.1016/j.dnarep.2005.03.005; JONES GDD, 1995, INT J RADIAT BIOL, V67, P647, DOI 10.1080/09553009514550761; KINSELLA TJ, 1987, INT J RADIAT ONCOL, V13, P733, DOI 10.1016/0360-3016(87)90292-6; KINSELLA TJ, 2005, ONCOLOGY EVIDENCE BA, P41; Kurz EU, 2004, DNA REPAIR, V3, P889, DOI 10.1016/j.dnarep.2004.03.029; LAWRENCE TS, 1990, RADIAT RES, V123, P192, DOI 10.2307/3577544; LAWRENCE TS, 1990, INT J RADIAT ONCOL, V18, P1393, DOI 10.1016/0360-3016(90)90313-9; Liu Lili, 2004, Curr Opin Investig Drugs, V5, P623; Liu LL, 2002, CLIN CANCER RES, V8, P2985; Liu LL, 2003, MOL CANCER THER, V2, P1061; Lowe SW, 2004, NATURE, V432, P307, DOI 10.1038/nature03098; MILLER EM, 1992, RADIAT RES, V131, P81, DOI 10.2307/3578320; Pawlik TM, 2004, INT J RADIAT ONCOL, V59, P928, DOI 10.1016/j.ijrobp.2004.03.005; Shay JW, 2004, ONCOGENE, V23, P2919, DOI 10.1038/sj.onc.1207518; Taverna P, 2003, CANCER RES, V63, P838; TURNER DP, IN PRESS CANC RES; Vallerga Anne K, 2004, Clin Adv Hematol Oncol, V2, P793; Veigl ML, 1998, P NATL ACAD SCI USA, V95, P8698, DOI 10.1073/pnas.95.15.8698; Watanabe R, 2002, INT J RADIAT BIOL, V78, P953, DOI 10.1080/0955300021000024270; Yan T, 2003, CLIN CANCER RES, V9, P2327; Yan T, 2001, CANCER RES, V61, P8290	33	22	23	0	3	AMER ASSOC CANCER RESEARCH	PHILADELPHIA	615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA	1535-7163	1538-8514		MOL CANCER THER	Mol. Cancer Ther.	APR	2006	5	4					893	902		10.1158/1535-7163.MCT-05-0364			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	041LU	WOS:000237458500012	16648559				2022-04-25	
J	Chaachouay, H; Fehrenbacher, B; Toulany, M; Schaller, M; Multhoff, G; Rodemann, HP				Chaachouay, Hassan; Fehrenbacher, Birgit; Toulany, Mahrnoud; Schaller, Martin; Multhoff, Gabriele; Rodemann, H. Peter			AMPK-independent autophagy promotes radioresistance of human tumor cells under clinical relevant hypoxia in vitro	RADIOTHERAPY AND ONCOLOGY			English	Article; Proceedings Paper	14th International Wolfsberg Meeting on Molecular Radiation Biology/Oncology	JUL 20-22, 2015	Wolfsberg, AUSTRIA	ESTRO		Clinical relevant hypoxia; Autophagy; Ionizing radiation; Solid tumor cells	RADIATION; SURVIVAL; CONTRIBUTES; EXPRESSION; INDUCTION; RESISTANT; BNIP3; ULK1	Background and purpose: Blocking of the autophagy-signaling has the potential to improve cancer therapy. In the present study, the role of autophagy for radioresistance of human tumor cells was tested under clinically relevant hypoxia (1% O-2). Materials and methods: Non-small cell lung cancer cell lines A549 and H460, head and neck squamous cell carcinoma FaDu, colon carcinoma cell line HCT116 and mouse-embryo-fibroblasts were analyzed under normoxic (21% O-2) and hypoxic (0.01% and 1% O-2) conditions with respect to clonogenic cell survival and hypoxia-induced autophagy. Immunofluorescence and electron microscopy were used to monitor the autophagy process and Western blotting of LC3, AMPK, and BNIP3 was applied to analyze autophagy signaling. Results: Clinically relevant hypoxia stimulated autophagy in tumor cells as indicated by enhanced LC3-I to LC3-II conversion. Furthermore, hypoxia stimulated autophagy was approved by Immunofluorescence staining and electron-microscopy analysis of autophagosome vacuoles. Preconditioning of tumor cells to moderate-hypoxia increased their radioresistance that was significantly reversed following pretreatment with autophagy inhibitor, chloroquine. Using siRNA against AMPK as well as AMPK deficient cells, autophagy stimulation by 1% O-2 was shown to be AMPK-independent. However, a correlation between the expression of BNIP3 and autophagy-stimulation was observed under this condition. Conclusion: Under clinically relevant hypoxia (1% O-2) the stimulation of autophagy mediates resistance of hypoxic tumor cells to ionizing radiation, which is independent of AMPK signaling. (C) 2015 Elsevier Ireland Ltd. All rights reserved.	[Chaachouay, Hassan; Toulany, Mahrnoud; Rodemann, H. Peter] Univ Tubingen, Div Radiobiol & Mol Environm Res, Dept Radiat Oncol, D-72076 Tubingen, Germany; [Fehrenbacher, Birgit; Schaller, Martin] Univ Tubingen, Dept Dermatol, D-72076 Tubingen, Germany; [Chaachouay, Hassan; Multhoff, Gabriele] Tech Univ Munich, Dept Radiat Oncol, D-80290 Munich, Germany; [Chaachouay, Hassan; Multhoff, Gabriele] HMGU CCG Innate Immun Tumor Biol, Munich, Germany; [Chaachouay, Hassan] Univ Zurich, Vetsuisse Fac, Sect Radiat Oncol, CH-8006 Zurich, Switzerland		Rodemann, HP (corresponding author), Univ Tubingen, Div Radiobiol & Mol Environm Res, Dept Radiat Oncol, Rontgenweg 11, D-72076 Tubingen, Germany.	hans-peter.rodemann@uni-tuebingen.de	Multhoff, Gabriele/AAW-9796-2021	Multhoff, Gabriele/0000-0002-2616-3137; Chaachouay, Hassan/0000-0002-9100-2612	Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [SFB-773 TP-B2, Ro 572/7-1, SFB773 TP-Z2]; DFG-Graduate SchoolGerman Research Foundation (DFG) [SFB773];  [SFB824/II]	This work was supported by the Deutsche Forschungsgemeinschaft by grants awarded to HPR (SFB-773 TP-B2 and Ro 572/7-1) and to MS (SFB773 TP-Z2). HC received a fellowship of the SFB773 associated DFG-Graduate School and GM received funding from the SFB824/II. The support of Dr. Tassula Proikas-Cezanne (Institute of Cell Biology, University of Tubingen) and Benoit Viollet, PhD (Institut Cochin, INSERM U1016, CNRS UMR 8104, Universite Paris Descartes, France) who provided the AMPK proficient and deficient MEF is gratefully acknowledged.	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Oncol.	SEP	2015	116	3					409	416		10.1016/j.radonc.2015.08.012			8	Oncology; Radiology, Nuclear Medicine & Medical Imaging	Science Citation Index Expanded (SCI-EXPANDED); Conference Proceedings Citation Index - Science (CPCI-S)	Oncology; Radiology, Nuclear Medicine & Medical Imaging	CU8UN	WOS:000363819700013	26318663				2022-04-25	
J	Li, Y; Li, W; Hoffman, AR; Cui, JW; Hu, JF				Li, Yan; Li, Wei; Hoffman, Andrew R.; Cui, Jiuwei; Hu, Ji-Fan			The Nucleus/Mitochondria-Shuttling LncRNAs Function as New Epigenetic Regulators of Mitophagy in Cancer	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY			English	Review						mitochondria; mitophagy; cancer metabolism; long non-coding RNA; cancer stem cells; cancer therapy	LONG NONCODING RNAS; HEPATOCELLULAR-CARCINOMA CELL; COLORECTAL-CANCER; MITOCHONDRIAL CLEARANCE; DAMAGED MITOCHONDRIA; GLUCOSE-METABOLISM; PARKIN ISOFORMS; HIGH EXPRESSION; BNIP3 PROTEIN; TARGET GENE	Mitophagy is a specialized autophagic pathway responsible for the selective removal of damaged or dysfunctional mitochondria by targeting them to the autophagosome in order to maintain mitochondria quality. The role of mitophagy in tumorigenesis has been conflicting, with the process both supporting tumor cell survival and promoting cell death. Cancer cells may utilize the mitophagy pathway to augment their metabolic requirements and resistance to cell death, thereby leading to increased cell proliferation and invasiveness. This review highlights major regulatory pathways of mitophagy involved in cancer. In particular, we summarize recent progress regarding how nuclear-encoded long non-coding RNAs (lncRNAs) function as novel epigenetic players in the mitochondria of cancer cells, affecting the malignant behavior of tumors by regulating mitophagy. Finally, we discuss the potential application of regulating mitophagy as a new target for cancer therapy.	[Li, Yan; Li, Wei; Cui, Jiuwei; Hu, Ji-Fan] First Hosp Jilin Univ, Ctr Canc, Key Lab Organ Regenerat & Transplantat, Minist Educ, Changchun, Peoples R China; [Li, Yan; Hoffman, Andrew R.; Hu, Ji-Fan] Stanford Univ, VA Palo Alto Hlth Care Syst, Med Sch, Palo Alto, CA 94305 USA		Cui, JW; Hu, JF (corresponding author), First Hosp Jilin Univ, Ctr Canc, Key Lab Organ Regenerat & Transplantat, Minist Educ, Changchun, Peoples R China.; Hu, JF (corresponding author), Stanford Univ, VA Palo Alto Hlth Care Syst, Med Sch, Palo Alto, CA 94305 USA.	cuijw@jlu.edu.cn; jifan@stanford.edu		Hoffman, Andrew/0000-0002-0145-1917	National Key R&D Program of China [2018YFA0106902]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [82050003, 81900701, 31430021, 81874052, 81672275, 31871297, 81670143, 32000431]; Key Project of Chinese Ministry of EducationMinistry of Education, China [311015]; National Basic Research Program of China (973 Program)National Basic Research Program of China [2015CB943303]; Nation Key Research and Development Program of China grant [2016YFC13038000]; Research on Chronic Non-communicable Diseases Prevention and Control of National Ministry of Science and Technology [2016YFC1303804]; National Health Development Planning Commission Major Disease Prevention and Control of Science and Technology Plan of Action, Cancer Prevention and Control [ZX-07-C2016004]; Natural Science Foundation of Jilin Province [20200801046GH, 20150101176JC, 20180101117JC, 20130413010GH]; Provincial Science Fund of Jilin Province Development and Reform Commission [2014N147, 2017C022]; 10th Youth Fund of First Hospital of Jilin University [JDYY 102019034]; California Institute of Regenerative Medicine (CIRM)California Institute for Regenerative Medicine [RT2-01942]; Biomedical Research Service of the Department of Veterans AffairsUS Department of Veterans Affairs [BX002905]	This work was supported by the National Key R&D Program of China (2018YFA0106902), the National Natural Science Foundation of China (82050003, 81900701, 31430021, 81874052, 81672275, 31871297, 81670143, 81900701, and 32000431), the Key Project of Chinese Ministry of Education grant (311015), the National Basic Research Program of China (973 Program; 2015CB943303), the Nation Key Research and Development Program of China grant (2016YFC13038000), Research on Chronic Non-communicable Diseases Prevention and Control of National Ministry of Science and Technology (2016YFC1303804), the National Health Development Planning Commission Major Disease Prevention and Control of Science and Technology Plan of Action, Cancer Prevention and Control (ZX-07-C2016004), the Natural Science Foundation of Jilin Province (20200801046GH, 20150101176JC, 20180101117JC, and 20130413010GH), the Provincial Science Fund of Jilin Province Development and Reform Commission (2014N147 and 2017C022), the 10th Youth Fund of First Hospital of Jilin University (JDYY 102019034), California Institute of Regenerative Medicine (CIRM) grant (RT2-01942), and the Biomedical Research Service of the Department of Veterans Affairs (BX002905).	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Cell. Dev. Biol.	SEP 8	2021	9								699621	10.3389/fcell.2021.699621			14	Cell Biology; Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Developmental Biology	US7SG	WOS:000697626300001	34568319	gold, Green Published			2022-04-25	
J	Rovito, D; Giordano, C; Vizza, D; Plastina, P; Barone, I; Casaburi, I; Lanzino, M; De Amicis, F; Sisci, D; Mauro, L; Aquila, S; Catalano, S; Bonofiglio, D; Ando, S				Rovito, Daniela; Giordano, Cinzia; Vizza, Donatella; Plastina, Pierluigi; Barone, Ines; Casaburi, Ivan; Lanzino, Marilena; De Amicis, Francesca; Sisci, Diego; Mauro, Loredana; Aquila, Saveria; Catalano, Stefania; Bonofiglio, Daniela; Ando, Sebastiano			Omega-3 PUFA ethanolamides DHEA and EPEA induce autophagy through PPAR gamma activation in MCF-7 breast cancer cells	JOURNAL OF CELLULAR PHYSIOLOGY			English	Article							POLYUNSATURATED FATTY-ACIDS; EICOSAPENTAENOIC ACID; RECEPTOR-GAMMA; GENE-EXPRESSION; N-ACYLETHANOLAMINES; COLON-CANCER; OMEGA-3-FATTY-ACIDS; APOPTOSIS; BINDING; BCL-2	The omega-3 long chain polyunsaturated fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), elicit anti-proliferative effects in cancer cell lines and in animal models. Dietary DHA and EPA can be converted to their ethanolamide derivatives, docosahexaenoyl ethanolamine (DHEA), and eicosapentaenoyl ethanolamine (EPEA), respectively; however, few studies are reported on their anti-cancer activities. Here, we demonstrated that DHEA and EPEA were able to reduce cell viability in MCF-7 breast cancer cells whereas they did not elicit any effects in MCF-10A non-tumorigenic breast epithelial cells. Since DHA and EPA are ligands of Peroxisome Proliferator-Activated Receptor gamma (PPAR), we sought to determine whether PPAR may also mediate DHEA and EPEA actions. In MCF-7 cells, both compounds enhanced PPAR expression, stimulated a PPAR response element-dependent transcription as confirmed by the increased expression of its target gene PTEN, resulting in the inhibition of AKT-mTOR pathways. Besides, DHEA and EPEA treatment induced phosphorylation of Bcl-2 promoting its dissociation from beclin-1 which resulted in autophagy induction. We also observed an increase of beclin-1 and microtubule-associated protein 1 light chain 3 expression along with an enhanced autophagosomes formation as revealed by mono-dansyl-cadaverine staining. Finally, we demonstrated the involvement of PPAR in DHEA- and EPEA-induced autophagy by using siRNA technology and a selective inhibitor. In summary, our data show that the two omega-3 ethanolamides exert anti-proliferative effects by inducing autophagy in breast cancer cells highlighting their potential use as breast cancer preventive and/or therapeutic agents. J. Cell. Physiol. 228: 13141322, 2013. (c) 2012 Wiley Periodicals, Inc.	[Rovito, Daniela; Vizza, Donatella; Casaburi, Ivan; Lanzino, Marilena; De Amicis, Francesca; Sisci, Diego; Aquila, Saveria; Catalano, Stefania; Bonofiglio, Daniela] Univ Calabria, Dept Pharmacobiol, Arcavacata Di Rende, CS, Italy; [Giordano, Cinzia; Barone, Ines; Ando, Sebastiano] Univ Calabria, Ctr Sanit, Arcavacata Di Rende, CS, Italy; [Plastina, Pierluigi] Univ Calabria, Dept Pharmaceut Sci, Arcavacata Di Rende, CS, Italy; [Barone, Ines; Mauro, Loredana; Ando, Sebastiano] Univ Calabria, Arcavacata Di Rende, CS, Italy		Ando, S (corresponding author), Univ Calabria, Dept Cell Biol, I-87036 Cosenza, Italy.	daniela.bonofiglio@tin.it; sebastiano.ando@unical.it	/AAD-9701-2019; Bonofiglio, Daniela/AAV-8371-2020	/0000-0001-6577-1541; Lanzino, Marilena/0000-0002-6362-5396; Rovito, Daniela/0000-0001-5390-5477; BONOFIGLIO, Daniela/0000-0002-4142-0496; GIORDANO, Cinzia/0000-0003-4969-0607; CATALANO, Stefania/0000-0002-6352-9628; AQUILA, Saveria/0000-0003-4738-6927; De Amicis, Francesca/0000-0001-7079-1037; BARONE, Ines/0000-0002-9769-1615	Associazione Italiana Ricerca sul Cancro (AIRC)Fondazione AIRC per la ricerca sul cancro [IG 11595]; Reintegration AIRC/Marie Curie International Fellowship; AIRC MFAGFondazione AIRC per la ricerca sul cancro [6180]; MURSTMinistry of Education, Universities and Research (MIUR); Lilli Funaro Foundation; FSE (Fondo Sociale Europeo); Calabria RegionRegione Calabria	Contract grant sponsor: Associazione Italiana Ricerca sul Cancro (AIRC) IG 11595.; Contract grant sponsor: Reintegration AIRC/Marie Curie International Fellowship.; Contract grant sponsor: AIRC MFAG 6180.; Contract grant sponsor: MURST and Ex 60%.; Contract grant sponsor: Lilli Funaro Foundation.; Contract grant sponsor: FSE (Fondo Sociale Europeo) and Calabria Region.	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Cell. Physiol.	JUN	2013	228	6					1314	1322		10.1002/jcp.24288			9	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	096OL	WOS:000315414000021	23168911				2022-04-25	
J	Du, RN; Zhao, PW; Wu, SK; Gao, YX; Wu, RN; Yang, ML; Song, WY; Gao, HN				Du, Rina; Zhao, Pengwei; Wu, Shikui; Gao, Yaoxing; Wu, Rina; Yang, Minli; Song, Wanying; Gao, Haining			Sendeng-4 Suppressed Melanoma Growth by Induction of Autophagy and Apoptosis	EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE			English	Article							BECLIN-1; LC3; CANCER	Sendeng-4 is a traditional Chinese medicine that has been successfully applied to anti-inflammatory diseases in clinical practice. Monomers within Sendeng-4 showed promising antitumor activity against lung cancer, colon cancer, and cutaneous cancer. However, potency of Sendeng-4 in melanoma has not been explored. This study aims to explore the potential application of Sendeng-4 in melanoma treatment. In the present study, we systemically investigate the possibility of Sendeng-4 for treatment of melanoma cancer in vitro by proliferation assay, colony formation, flow cell cytometry, RNA-seq, western blot, and fluorescence-based assay. Our data demonstrated that Sendeng-4 suppresses the proliferation and colony formation capacity of melanoma cells and induces cell cycle block at G2/M phase and eventually cell death. Mechanistically, transcriptome sequencing demonstrates that the PI3K-AKT pathway was significantly inactivated upon Sendeng-4 exposure, which was confirmed by western blot showing decreased phosphorylation of AKT. In addition, decreased BCL-2 expression and increased BAX expression were observed, suggesting programmed cell death via apoptosis. Moreover, LC3-II production as well as autophagosomes formation was observed as demonstrated by western blot and immunofluorescence, indicating elevated autophagy network by Sendeng-4 stimulation. Collectively, we concluded that Sendeng-4 might be used as an anticancer drug for melanoma.	[Du, Rina] Inner Mongolian Int Mongolian Hosp, Wulanchabudong St, Hohhot 010090, Peoples R China; [Zhao, Pengwei; Song, Wanying; Gao, Haining] Inner Mongolia Med Univ, Sch Basic Med Sci, Lab Microbiol & Immunol, Xinhua St, Hohhot 010059, Peoples R China; [Wu, Shikui; Wu, Rina] Inner Mongolia Med Univ, Coll Pharm, Jinshan St, Hohhot 010010, Peoples R China; [Gao, Yaoxing] Inner Mongolia Med Univ, Affiliated Hosp, Tongdao St, Hohhot 010010, Peoples R China; [Yang, Minli] Inner Mongolia Baihanxumu Biotechnol Co LTD, Jinshan St, Hohhot 010010, Peoples R China		Zhao, PW (corresponding author), Inner Mongolia Med Univ, Sch Basic Med Sci, Lab Microbiol & Immunol, Xinhua St, Hohhot 010059, Peoples R China.; Gao, YX (corresponding author), Inner Mongolia Med Univ, Affiliated Hosp, Tongdao St, Hohhot 010010, Peoples R China.	rina_du@163.com; pengwzhao@126.com; shikuiwu@yahoo.com; gaoyaoxing1506@163.com; wurinawu506@hotmail.com; 895758757@qq.com; swy7990@126.com; 1766768147@qq.com		zhao, pengwei/0000-0002-2526-5705	Inner Mongolia Major Science and Technology Projects	This work was supported by Inner Mongolia Major Science and Technology Projects (Study of Mongolian medicine Sendeng-4 and development of its related nanocosmeceutical products).	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J	Wang, GY; Zhang, T; Sun, W; Wang, HS; Yin, F; Wang, ZY; Zuo, DQ; Sun, MX; Zhou, ZF; Lin, BH; Xu, J; Hua, YQ; Li, HQ; Cai, ZD				Wang, Gangyang; Zhang, Tao; Sun, Wei; Wang, Hongsheng; Yin, Fei; Wang, Zhuoying; Zuo, Dongqing; Sun, Mengxiong; Zhou, Zifei; Lin, Binhui; Xu, Jing; Hua, Yingqi; Li, Haoqing; Cai, Zhengdong			Arsenic sulfide induces apoptosis and autophagy through the activation of ROS/JNK and suppression of Akt/mTOR signaling pathways in osteosarcoma	FREE RADICAL BIOLOGY AND MEDICINE			English	Article						Arsenic sulfide; Apoptosis; Autophagy; Osteosarcoma; Call cycle	ACUTE PROMYELOCYTIC LEUKEMIA; ROS-MEDIATED MECHANISMS; IN-VITRO; CELL-CYCLE; CANCER-CELLS; MOLECULAR-MECHANISMS; MITOTIC ARREST; TETRA-SULFIDE; GROWTH; DEATH	Osteosarcoma is a common primary malignant bone tumor, the cure rate of which has stagnated over the past 25-30 years. Arsenic sulfide (As2S2), the main active ingredient of the traditional Chinese medicine realgar, has been proved to have antitumor efficacy in several tumor types including acute promyelocytic leukemia, gastric cancer and colon cancer. Here, we investigated the efficacy and mechanism of As2S2 in osteosarcoma both in vitro and in vivo. In this study, we demonstrated that As2S2 potently suppressed cell proliferation by inducing G2/M phase arrest in various osteosarcoma cell lines. Also, treatment with As2S2 induced apoptosis and autophagy in osteosarcoma cells. The apoptosis induction was related to PARP cleavage and activation of caspase-3, -8, -9. As2S2 was demonstrated to induce autophagy as evidenced by formation of autophagokme and accumulation of LC3H. Further studies showed that As2S2-induced apoptosis and autophagy could be significantly attenuated by ROS scavenger and JNK inhibitor. Moreover, we found that As2S2 inhibited Akt/mTOR signaling pathway, and suppressing Akt and mTOR kinases activity can increase As2S2-induced apoptosis and autophagy. Finally, As2S2 in vivo suppressed tumor growth with few side effects. In summary, our results revealed that As2S2 induced G2/M phase arrest, apoptosis, and autophagy via activing ROS/JNK and blocking Altt/mTOR signaling pathway in human osteosarcoma cells. Arsenic sulfide may be a potential clinical antitumor drugs targeting osteosarcoma.	[Wang, Gangyang; Zhang, Tao; Sun, Wei; Wang, Hongsheng; Yin, Fei; Wang, Zhuoying; Zuo, Dongqing; Sun, Mengxiong; Zhou, Zifei; Lin, Binhui; Xu, Jing; Hua, Yingqi; Li, Haoqing; Cai, Zhengdong] Shanghai Jiao Tong Univ, Dept Orthopaed, Shanghai Bone Tumor Inst, Shanghai Gen Hosp,Sch Med, Shanghai, Peoples R China; [Wang, Hongsheng] Tongji Univ, Yangpu Hosp, Dept Orthopaed, Sch Med, Shanghai, Peoples R China; [Zuo, Dongqing] Tongji Univ, Shanghai Peoples Hosp 10, Dept Orthopaed, Sch Med, Shanghai, Peoples R China; [Zhou, Zifei] Tongji Univ, Shanghai East Hosp, Dept Orthopaed, Shanghai, Peoples R China; [Wang, Gangyang; Zhang, Tao; Sun, Wei; Wang, Hongsheng; Yin, Fei; Wang, Zhuoying; Zuo, Dongqing; Sun, Mengxiong; Zhou, Zifei; Lin, Binhui; Xu, Jing; Hua, Yingqi; Li, Haoqing; Cai, Zhengdong] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, 100 Haining Rd Shanghai, Shanghai, Peoples R China		Hua, YQ; Li, HQ; Cai, ZD (corresponding author), Shanghai Jiao Tong Univ, Dept Orthopaed, Shanghai Bone Tumor Inst, Shanghai Gen Hosp,Sch Med, Shanghai, Peoples R China.	gangyang_wang@163.com; zhangtaoabc@2008.sina.com; viv-sun@163.com; wanghs1231@gmail.com; yinfeicat@163.com; wyz135@163.com; zuozuo198@163.com; sunmensiong@126.com; zhouzf@yeah.net; nylbh7581@163.com; piao_hay@163.com; hua_yingqi@163.com; lihaoqing@medmail.com; czd856@vip.163.com			National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81502604]; Shanghai Science and Technology CommissionShanghai Science & Technology CommitteeScience & Technology Commission of Shanghai Municipality (STCSM) [14140904000]; School of Medicine, Shanghai Jiao Tong University [81450110092]; Shanghai Hospital Development Center [SHDC12013107]	This work was supported by the National Natural Science Foundation (No. 81502604); Shanghai Science and Technology Commission (No. 14140904000); School of Medicine, Shanghai Jiao Tong University (No. 81450110092) and Research Grant from Shanghai Hospital Development Center (No. SHDC12013107).	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Biol. Med.	MAY	2017	106						24	37		10.1016/j.freeradbiomed.2017.02.015			14	Biochemistry & Molecular Biology; Endocrinology & Metabolism	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Endocrinology & Metabolism	EU0TN	WOS:000400724500003	28188923				2022-04-25	
J	McAllister, SD; Soroceanu, L; Desprez, PY				McAllister, Sean D.; Soroceanu, Liliana; Desprez, Pierre-Yves			The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids	JOURNAL OF NEUROIMMUNE PHARMACOLOGY			English	Review						Cannabinoid; Cannabidiol; Cancer; Reactive oxygen species	CANNABIDIOL-INDUCED APOPTOSIS; CANCER-CELL INVASION; ENDOCANNABINOID SYSTEM; POSSIBLE INVOLVEMENT; TUMOR-GROWTH; INHIBITION; DELTA-9-TETRAHYDROCANNABINOL; THERAPY; TETRAHYDROCANNABINOL; AUTOPHAGY	As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Delta(9)-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers. In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors. For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer. This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells. We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.	[McAllister, Sean D.; Soroceanu, Liliana; Desprez, Pierre-Yves] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA		McAllister, SD (corresponding author), Calif Pacific Med Ctr, Res Inst, 475 Brannan St,Suite 220, San Francisco, CA 94107 USA.	mcallis@cpmcri.org			NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA135281] Funding Source: NIH RePORTER; NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01 CA135281] Funding Source: Medline		AGURELL S, 1981, EXPERIENTIA, V37, P1090, DOI 10.1007/BF02085029; ALBANESE C, 1995, J BIOL CHEM, V270, P23589, DOI 10.1074/jbc.270.40.23589; ALOZIE SO, 1980, PHARMACOL BIOCHEM BE, V12, P217, DOI 10.1016/0091-3057(80)90359-7; Armstrong JL, 2015, J INVEST DERMATOL; Baldwin JM, 1994, CURR OPIN CELL BIOL, V6; Bifulco M, 2002, NAT MED, V8, P547, DOI 10.1038/nm0602-547; Bornheim LM, 1998, CHEM RES TOXICOL, V11, P1209, DOI 10.1021/tx9800598; BRADY KT, 1980, PSYCHOPHARMACOLOGY, V72, P21, DOI 10.1007/BF00433803; Caffarel MM, 2010, MOL CANCER, V9, DOI 10.1186/1476-4598-9-196; Cardaci S, 2012, J CELL SCI, V125, P2115, DOI 10.1242/jcs.095216; Carracedo A, 2006, CANCER CELL, V9, P301, DOI 10.1016/j.ccr.2006.03.005; Carracedo A, 2006, CANCER RES, V66, P6748, DOI 10.1158/0008-5472.CAN-06-0169; DALTON WS, 1976, CLIN PHARMACOL THER, V19, P300; Dando I, 2013, CELL DEATH DIS, V4, DOI 10.1038/cddis.2013.151; DAVIS WM, 1983, GEN PHARMACOL, V14, P247, DOI 10.1016/0306-3623(83)90004-6; De Petrocellis L, 2013, BRIT J PHARMACOL, V168, P79, DOI 10.1111/j.1476-5381.2012.02027.x; Donadelli M, 2011, CELL DEATH DIS, V2, DOI 10.1038/cddis.2011.36; EDERY H, 1971, ANN NY ACAD SCI, V191, P40, DOI 10.1111/j.1749-6632.1971.tb13985.x; Elbaz M, 2015, MOL ONCOL; Emery SM, 2014, J PHARMACOL EXP THER, V348, P293, DOI 10.1124/jpet.113.205120; Flygare J, 2008, SEMIN CANCER BIOL, V18, P176, DOI 10.1016/j.semcancer.2007.12.008; Fong S, 2003, P NATL ACAD SCI USA, V100, P13543, DOI 10.1073/pnas.2230238100; Freimuth N, 2010, J PHARMACOL EXP THER, V332, P336, DOI 10.1124/jpet.109.157735; Galve-Roperh I, 2000, NAT MED, V6, P313, DOI 10.1038/73171; GUIMARAES FS, 1994, GEN PHARMACOL, V25, P161, DOI 10.1016/0306-3623(94)90027-2; Guindon J, 2011, BRIT J PHARMACOL, V163, P1447, DOI 10.1111/j.1476-5381.2011.01327.x; Gupta GP, 2007, P NATL ACAD SCI USA, V104, P19506, DOI 10.1073/pnas.0709185104; Hampson AJ, 1998, P NATL ACAD SCI USA, V95, P8268, DOI 10.1073/pnas.95.14.8268; HILTUNEN AJ, 1988, PHARMACOL BIOCHEM BE, V30, P675, DOI 10.1016/0091-3057(88)90082-2; HILTUNEN AJ, 1989, NEUROPHARMACOLOGY, V28, P183, DOI 10.1016/0028-3908(89)90055-5; Holland ML, 2007, BRIT J PHARMACOL, V152, P815, DOI 10.1038/sj.bjp.0707467; Holland ML, 2006, BIOCHEM PHARMACOL, V71, P1146, DOI 10.1016/j.bcp.2005.12.033; HOLLISTER LE, 1975, CLIN PHARMACOL THER, V18, P80; HOWLETT AC, 1987, NEUROPHARMACOLOGY, V26, P507, DOI 10.1016/0028-3908(87)90035-9; Hu H, 2009, ONCOL REP, V21, P1053, DOI 10.3892/or_00000323; Huffman JW, 1996, J MED CHEM, V39, P3875, DOI 10.1021/jm960394y; HUNT CA, 1981, J PHARMACOKINET BIOP, V9, P245, DOI 10.1007/BF01059266; Jacobsson SOP, 2000, BIOCHEM PHARMACOL, V60, P1807, DOI 10.1016/S0006-2952(00)00492-5; Jaeger W, 1996, XENOBIOTICA, V26, P275, DOI 10.3109/00498259609046707; JARBE TUC, 1987, NEUROPHARMACOLOGY, V26, P219, DOI 10.1016/0028-3908(87)90212-7; Karler R., 1979, MARIHUANA BIOL EFFEC, P619, DOI [10.1016/b978-0-08-023759-6.50052-4, DOI 10.1016/B978-0-08-023759-6.50052-4, 10.1016/B978-0-08-023759-6.50052-4]; Klein TW, 2005, NAT REV IMMUNOL, V5, P400, DOI 10.1038/nri1602; Kogan NM, 2007, MOL CANCER THER, V6, P173, DOI 10.1158/1535-7163.MCT-06-0039; Kogan NM, 2004, J MED CHEM, V47, P3800, DOI 10.1021/jm040042o; Laurent A, 2005, CANCER RES, V65, P948; Ligresti A, 2006, J PHARMACOL EXP THER, V318, P1375, DOI 10.1124/jpet.106.105247; Malfait AM, 2000, P NATL ACAD SCI USA, V97, P9561, DOI 10.1073/pnas.160105897; Mao P, 2013, P NATL ACAD SCI USA, V110, P8644, DOI 10.1073/pnas.1221478110; Marcu JP, 2010, MOL CANCER THER, V9, P180, DOI 10.1158/1535-7163.MCT-09-0407; Massi P, 2008, J NEUROCHEM, V104, P1091, DOI 10.1111/j.1471-4159.2007.05073.x; Massi P, 2006, CELL MOL LIFE SCI, V63, P2057, DOI 10.1007/s00018-006-6156-x; Massi P, 2004, J PHARMACOL EXP THER, V308, P838, DOI 10.1124/jpet.103.061002; Massi P, 2013, BRIT J CLIN PHARMACO, V75, P303, DOI 10.1111/j.1365-2125.2012.04298.x; Mato S, 2010, GLIA, V58, P1739, DOI 10.1002/glia.21044; McAllister SD, 2007, MOL CANCER THER, V6, P2921, DOI 10.1158/1535-7163.MCT-07-0371; McAllister SD, 2011, BREAST CANCER RES TR, V129, P37, DOI 10.1007/s10549-010-1177-4; McKallip RJ, 2006, MOL PHARMACOL, V70, P897, DOI 10.1124/mol.106.023937; McPartland J. 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Neuroimmune Pharm.	JUN	2015	10	2					255	267		10.1007/s11481-015-9608-y			13	Neurosciences; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Neurosciences & Neurology; Pharmacology & Pharmacy	CK5WF	WOS:000356296100007	25916739	Green Accepted			2022-04-25	
J	Zhang, W; Li, QY; Song, C; Lao, LF				Zhang, Wei; Li, Qianyi; Song, Chao; Lao, Lifeng			Knockdown of autophagy-related protein 6, Beclin-1, decreases cell growth, invasion, and metastasis and has a positive effect on chemotherapy-induced cytotoxicity in osteosarcoma cells	TUMOR BIOLOGY			English	Article						Autophagy; Beclin-1; Proliferation; Invasion; Chemoresistance	CANCER-THERAPY; APOPTOSIS; DEATH; INHIBITION; ACTIVATION; MATRIX-METALLOPROTEINASE-9; CHEMOSENSITIVITY; RESISTANCE; INDUCTION; MIGRATION	Beclin-1, a well-known key regulator of autophagy, has been implicated in many disorders, including cancer, aging, and degenerative diseases. Previous studies demonstrated that Beclin-1 participated in tumorgenesis and was highly expressed in colorectal cancer cells, primary duodenal adenocarcinoma, and hepatocellular carcinoma cells, and overexpression of Beclin-1 could induce autophagic cell death in leukemia cells. However, the exact effects and molecular mechanisms of Beclin-1-mediated autophagy in osteosarcoma are still unknown up to now. Here, we evaluated the role of Beclin-1 in human osteosarcoma cell lines in vivo and in vitro. In order to characterize the endogenous expression of Beclin-1 in osteosarcoma cell lines, we performed real-time PCR and Western blot analysis. We further analyzed the level of Beclin-1 in osteosarcoma cells after chemotherapy and investigated the impact of autophagy inhibition on chemotherapy-induced cytotoxicity. We used the small interfering RNA (siRNA) directed against Beclin-1 to infect the osteosarcoma cell line with relatively high Belcin-1 expression. Furthermore, we determine the functional relevance of Beclin-1 knockdown to osteosarcoma cell growth, migration, and invasion, and investigate the expression levels of matrix metallopeptidase-2 (MMP-2), MMP-9, phosphoinositide 3-kinase p85 alpha (PI3Kp85 alpha), and phosphorylated AKT (p-AKT). As a result, HOS osteosarcoma cells exhibited higher Beclin-1 expression. Anticancer agents including doxorubicin, cisplatin, and methotrexate each induced Beclin-1 up-regulation in human osteosarcoma cells, and siRNA-mediated knockdown of Beclin-1 suppressed cell proliferation, migration, and invasion indicated by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenylthetrazolium bromide, would healing, and transwell assays. Cell apoptosis induced by anticancer agents was markedly increased. Knockdown of Beclin-1 or inhibition of autophagy by 3-methyladenine (an inhibitor of autophagy and PI3K) rendered them significantly more sensitive to chemotherapy. Addition of the pan-caspase inhibitor ZVAD-FMK partly reversed the cisplatin-induced cell death. When Beclin-1 expression was inhibited, the expression of PI3Kp85 alpha, p-AKT, and MMP-9 was downregulated in HOS cells. In addition, the tumor volumes in subcutaneous nude mouse models in Beclin-1-deleted HOS cells were significantly smaller than those of control group. These results suggested that knockdown of Beclin-1 by siRNA exerts inhibitory effects on growth and migration of osteosarcoma cells possibly via blockade of the PI3K/AKT signaling. Beclin-1 knockdown rendered them significantly more sensitive to chemotherapy through activating apoptosis pathway. The results of this study suggest that Beclin-1 plays an important role in proliferation and tumor progression in osteosarcoma and inhibition autophagy can increase the efficacy of anticancer agent therapy.	[Zhang, Wei; Li, Qianyi; Song, Chao; Lao, Lifeng] Shanghai Jiao Tong Univ, Dept Orthopaed Surg, Renji Hosp, Sch Med, Shanghai 200127, Peoples R China		Lao, LF (corresponding author), Shanghai Jiao Tong Univ, Dept Orthopaed Surg, Renji Hosp, Sch Med, Shanghai 200127, Peoples R China.	WZhangDoctor@163.com; QLi667@126.com; CSongspine@163.com; laolifeng@gmail.com			National Natural Science Foundation of Youth Program [81101394]; Shanghai Special Fund for Outstanding Young Teachers in Universities [JDY10080]; Shanghai Renji Hospital Fund for Outstanding Youth [RJPY10-010]; Shanghai Fund for Young Physician Development [20141051]	This work was supported by the grants from the National Natural Science Foundation of Youth Program (No. 81101394), Shanghai Special Fund for Outstanding Young Teachers in Universities (No. JDY10080), Shanghai Renji Hospital Fund for Outstanding Youth (No. RJPY10-010), and Shanghai Fund for Young Physician Development (No. 20141051).	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APR	2015	36	4					2531	2539		10.1007/s13277-014-2868-y			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CF9LJ	WOS:000352885900038	25427639				2022-04-25	
J	Papademetrio, DL; Lompardia, SL; Simunovich, T; Costantino, S; Mihalez, CY; Cavaliere, V; Alvarez, E				Laura Papademetrio, Daniela; Laura Lompardia, Silvina; Simunovich, Tania; Costantino, Susana; Yamila Mihalez, Cintia; Cavaliere, Victoria; Alvarez, Elida			Inhibition of Survival Pathways MAPK and NF-kB Triggers Apoptosis in Pancreatic Ductal Adenocarcinoma Cells via Suppression of Autophagy	TARGETED ONCOLOGY			English	Article							FACTOR-KAPPA-B; GENE-EXPRESSION; SIGNALING PATHWAYS; CANCER-TREATMENT; LUNG-CANCER; ACTIVATION; INDUCTION; PROTEINS; COLON; RAS/RAF/MEK/ERK	Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a survival rate of 4-6 months from diagnosis. PDAC is the fourth leading cause of cancer-related death in the Western world, with a mortality rate of 10 cases per 100,000 population. Chemotherapy constitutes only a palliative strategy, with limited effects on life expectancy. Aims To investigate the biological response of PDAC to mitogen-activated protein kinase (MAPK) and NF-kappaB (NF-kB) inhibitors and the role of autophagy in the modulation of these signaling pathways in order to address the challenge of developing improved medical protocols for patients with PDAC. Methods Two ATCC cell lines, MIAPaCa-2 and PANC-1, were used as PDAC models. Cells were exposed to inhibitors of MAPK or NF-kB survival pathways alone or after autophagy inhibition. Several aspects were analyzed, as follows: cell proliferation, by [H-3] TdR incorporation; cell death, by TUNEL assay, regulation of autophagy by LC3-II expression level and modulation of pro-and anti-apoptotic proteins by Western blot. Results We demonstrated that the inhibition of the MAPK and NF-kB survival pathways with U0126 and caffeic acid phenethyl ester (CAPE), respectively, produced strong inhibition of pancreatic tumor cell growth without inducing apoptotic death. Interestingly, U0126 and CAPE induced apoptosis after autophagy inhibition in a caspase-dependent manner in MIA PaCa-2 cells and in a caspase-independent manner in PANC-1 cells. Conclusions Here we present evidence that allows us to consider a combined therapy regimen comprising an autophagy inhibitor and a MAPK or NF-kB pathway inhibitor as a possible treatment strategy for pancreatic cancer.	[Laura Papademetrio, Daniela; Laura Lompardia, Silvina; Simunovich, Tania; Costantino, Susana; Yamila Mihalez, Cintia; Cavaliere, Victoria; Alvarez, Elida] Univ Buenos Aires, Fac Farm & Bioquim, Catedra Inmunol, Junin 956,4 Piso, RA-1113 Buenos Aires, Buenos Aires, Argentina; [Laura Papademetrio, Daniela; Laura Lompardia, Silvina; Costantino, Susana; Yamila Mihalez, Cintia; Alvarez, Elida] Consejo Nacl Invest Cient & Tecn, IDEHU, RA-1033 Buenos Aires, Buenos Aires, Argentina		Papademetrio, DL; Alvarez, E (corresponding author), Univ Buenos Aires, Fac Farm & Bioquim, Catedra Inmunol, Junin 956,4 Piso, RA-1113 Buenos Aires, Buenos Aires, Argentina.; Papademetrio, DL; Alvarez, E (corresponding author), Consejo Nacl Invest Cient & Tecn, IDEHU, RA-1033 Buenos Aires, Buenos Aires, Argentina.	dpapademetrio@ffyb.uba.ar; elialv@ffyb.uba.ar	Lompardía, Silvina/AAF-7230-2021	Lompardia, Silvina/0000-0002-8499-5417; Papademetrio, Daniela/0000-0002-3419-5614	Universidad de Buenos AiresUniversity of Buenos Aires; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)	This study was funded by Universidad de Buenos Aires and Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET).	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Oncol.	APR	2016	11	2					183	195		10.1007/s11523-015-0388-3			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DI7QA	WOS:000373695200007	26373299				2022-04-25	
J	Dumas, JF; Brisson, L; Chevalier, S; Maheo, K; Fromont, G; Moussata, D; Besson, P; Roger, S				Dumas, Jean-Francois; Brisson, Lucie; Chevalier, Stephan; Maheo, Karine; Fromont, Gaelle; Moussata, Driffa; Besson, Pierre; Roger, Sebastien			Metabolic reprogramming in cancer cells, consequences on pH and tumour progression: Integrated therapeutic perspectives with dietary lipids as adjuvant to anticancer treatment	SEMINARS IN CANCER BIOLOGY			English	Review						Cancer cell metabolism; pH; Cancer cell invasiveness; Resistance to treatments; N-3 polyunsaturated fatty acids	POLYUNSATURATED FATTY-ACIDS; GATED SODIUM-CHANNELS; EPITHELIAL-MESENCHYMAL TRANSITION; NA+/H+ EXCHANGER NHE1; TRANSCRIPTION FACTOR SNAIL; BREAST-CANCER; COLON-CANCER; DOCOSAHEXAENOIC ACID; OXIDATIVE STRESS; EXTRACELLULAR PH	While tumours arise from acquired mutations in oncogenes or tumour-suppressor genes, it is clearly established that cancers are metabolic diseases characterized by metabolic alterations in tumour cells, and also non-tumour cells of the host organism resulting in tumour cachexia and patient weakness. In this review, we aimed at delineating details by which metabolic alterations in cancer cells, characterized by mitochondrial bioenergetics deregulations and the preference for aerobic glycolysis, are critical parameters controlling the aggressive progression of tumours. In particular, metabolic alteration in cancer cells are coupled to the modulation of intracellular and extracellular pH, epithelial-to-mesenchymal transition and associated increased invasiveness, autophagy, and the development of anticancer treatment resistance. Finally, based on mechanistic, pre-clinical and clinical studies, we proposed the adjuvant supplementation of dietary n-3 polyunsaturated fatty acids for a complementary holistic treatment of the cancer disease. (C) 2017 Elsevier Ltd. All rights reserved.	[Dumas, Jean-Francois; Brisson, Lucie; Chevalier, Stephan; Maheo, Karine; Fromont, Gaelle; Moussata, Driffa; Besson, Pierre; Roger, Sebastien] Univ Francois Rabelais Tours, INSERM, Nutr Croissance & Canc UMR1069, 10 Blvd Tonnelle, F-37032 Tours, France; [Dumas, Jean-Francois; Chevalier, Stephan; Maheo, Karine; Besson, Pierre] Univ Francois Rabelais Tours, UFR Sci Pharmaceut, Ave Monge, F-37200 Tours, France; [Fromont, Gaelle] CHU Tours, Serv Anat & Cytol Pathol, F-37044 Tours 9, France; [Moussata, Driffa] CHU Tours, Serv Hepatogastroenterol & Cancerol Digest, F-37044 Tours 9, France; [Roger, Sebastien] Univ Francois Rabelais Tours, UFR Sci & Tech, Dept Physiol Anim, Ave Monge, F-37200 Tours, France; [Roger, Sebastien] Inst Univ France, 1 Rue Descartes, F-75231 Paris, France		Roger, S (corresponding author), Univ Francois Rabelais Tours, INSERM, UMR 1069, 10 Blvd Tonnelle, F-37032 Tours, France.	sebastien.roger@univ-tours.fr	Maheo, Karine/AAC-3259-2022; fromont, gaelle/N-8708-2016; Dumas, Jean-François/AAN-5035-2020; Brisson, Lucie/R-1179-2016; Dumas, Jean-François/S-7486-2017	Dumas, Jean-François/0000-0002-2293-6606; Brisson, Lucie/0000-0001-7811-1382; Dumas, Jean-François/0000-0002-2293-6606; Roger, Sebastien/0000-0002-9852-5248	Ministere de la Recherche et des Technologies; InsermInstitut National de la Sante et de la Recherche Medicale (Inserm)European Commission; Ligue Nationale Contre le Cancer - Interregion Grand-Ouest; Region Centre-Val de LoireRegion Centre-Val de Loire; Centre Hospitalo-Universitaire of Tours; Association CANCEN; Studium; Canceropole Grand-Ouest; Institut Universitaire de France (IUF)	We thank all our colleagues from the Inserm UMR1069 for all constructive discussion and Catherine Le Roy for secretary and administrative assistance. The work performed at the Inserm UMR1069 was supported by the "Ministere de la Recherche et des Technologies", the Inserm, the "Ligue Nationale Contre le Cancer - Interregion Grand-Ouest", the Region Centre-Val de Loire (grant "NaVMetarget", project "ARD2020 Biomedicaments), the Centre Hospitalo-Universitaire of Tours, the "Association CANCEN", the "Studium" and the "Canceropole Grand-Ouest". SR is supported by the Institut Universitaire de France (IUF).	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J	Gil, J; Ramsey, D; Szmida, E; Leszczynski, P; Pawlowski, P; Bebenek, M; Sasiadek, MM				Gil, Justyna; Ramsey, David; Szmida, Elzbieta; Leszczynski, Przemyslaw; Pawlowski, Pawel; Bebenek, Marek; Sasiadek, Maria M.			The BAX gene as a candidate for negative autophagy-related genes regulator on mRNA levels in colorectal cancer	MEDICAL ONCOLOGY			English	Article						Autophagy; Apoptosis; Colorectal cancer; Relative expression	DOWN-REGULATION; EXPRESSION; PROTEIN; TUMOR; APOPTOSIS; BECLIN-1; MECHANISMS; METASTASIS; PCR	Autophagy is a catabolic process, which is involved in the maintenance of intracellular homeostasis by degrading redundant molecules and organelles. Autophagy begins with the formation of a double-membrane phago-phore, followed by its enclosure, thus leading to the appearance of an autophagosome which fuses with lysosome. This process is highly conserved, precisely orchestrated and regulated by autophagy-related genes. Recently, autophagy has been widely studied in different types of cancers, including colorectal cancer. As it has been revealed, autophagy plays two opposite roles in tumorigenesis, as a tumor suppressor and a tumor enhancer/activator, and therefore is called a double-edge sword. Recently, interaction between autophagy and apoptosis has been found. Therefore, we aimed to study the mRNA levels of genes engaged in autophagy and apoptosis in colorectal cancer tissues. Colorectal cancer and adjacent healthy tissues were obtained from 73 patients diagnosed with primary colorectal cancer. Real-time PCR analysis employing Universal Probe Library was used to assess the expression of the seven following selected genes: BECN1, UVRAG, ULK1, ATG13, Bif-1, BCL2 and BAX. For all but one of the tested genes, a decrease in expression was observed. An increase in expression was observed for BAX. BAX expression decreases consistently from early to more advanced stages. High expression of BAX was strongly associated with negative UVRAG expression. The high expression of the BAX gene seems to be a negative regulator of autophagy in colorectal cancer cells. The relative downregulation of autophagy-related genes was observed in colorectal cancer samples.	[Gil, Justyna; Szmida, Elzbieta; Pawlowski, Pawel; Sasiadek, Maria M.] Wroclaw Med Univ, Dept Genet, PL-50368 Wroclaw, Poland; [Ramsey, David] Wroclaw Univ Technol, Dept Operat Res, PL-50372 Wroclaw, Poland; [Leszczynski, Przemyslaw] Wroclaw Med Univ, Dept Biol & Med Parasitol, PL-50345 Wroclaw, Poland; [Bebenek, Marek] Lower Silesian Oncol Ctr, Dept Surg Oncol 1, PL-53413 Wroclaw, Poland		Gil, J (corresponding author), Wroclaw Med Univ, Dept Genet, PL-50368 Wroclaw, Poland.	justyna.gil@umed.wroc.pl	/L-5618-2019	/0000-0003-0991-7686; Bebenek, Marek/0000-0001-7716-5960; Szmida, Elzbieta/0000-0003-3108-0165; Sasiadek, Maria/0000-0002-7599-7074; Leszczynski, Przemyslaw/0000-0002-4181-4997	National Science Centre (Poland) [DEC-2012/07/D/NZ5/04305]	This work was financed from the funds of the National Science Centre (Poland) decision number DEC-2012/07/D/NZ5/04305.	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Oncol.	FEB	2017	34	2							16	10.1007/s12032-016-0869-y			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EK1MF	WOS:000393689000002	28035578	hybrid, Green Published			2022-04-25	
J	Malarz, K; Mularski, J; Kuczak, M; Mrozek-Wilczkiewicz, A; Musiol, R				Malarz, Katarzyna; Mularski, Jacek; Kuczak, Michal; Mrozek-Wilczkiewicz, Anna; Musiol, Robert			Novel Benzenesulfonate Scaffolds with a High Anticancer Activity and G2/M Cell Cycle Arrest	CANCERS			English	Article						styrylquinazoline; sulfonic derivatives; anticancer activity; cell cycle inhibition; G2; M phase; apoptosis; autophagy		Simple Summary Sulfonate derivatives have limited application in pharmacology. Only few examples of small-molecule alkylating agents used as DNA poisons are known. This is the first report presenting strong anticancer activity of aromatic sulfonates based on quinazolines. The screening revealed that compounds expressed good submicromolar activity exceeding imatinib against a panel of cancer cell lines, including leukemia, colon, pancreatic cancers and glioblastoma, and minimal effect on proliferation of non-cancer cells. This activity corresponds with strong cell cycle arrest and mitotic inhibition similar or higher than that of paclitaxel. Further investigation revealed a more multitargeted mechanism of action. This structure may be an effective, novel scaffold for drug design. Sulfonates, unlike their derivatives, sulphonamides, have rarely been investigated for their anticancer activity. Unlike the well-known sulphonamides, esters are mainly used as convenient intermediates in a synthesis. Here, we present the first in-depth investigation of quinazoline sulfonates. A small series of derivatives were synthesized and tested for their anticancer activity. Based on their structural similarity, these compounds resemble tyrosine kinase inhibitors and the p53 reactivator CP-31398. Their biological activity profile, however, was more related to sulphonamides because there was a strong cell cycle arrest in the G2/M phase. Further investigation revealed a multitargeted mechanism of the action that corresponded to the p53 protein status in the cell. Although the compounds expressed a high submicromolar activity against leukemia and colon cancers, pancreatic cancer and glioblastoma were also susceptible. Apoptosis and autophagy were confirmed as the cell death modes that corresponded with the inhibition of metabolic activity and the activation of the p53-dependent and p53-independent pathways. Namely, there was a strong activation of the p62 protein and GADD44. Other proteins such as cdc2 were also expressed at a higher level. Moreover, the classical caspase-dependent pathway in leukemia was observed at a lower concentration, which again confirmed a multitargeted mechanism. It can therefore be concluded that the sulfonates of quinazolines can be regarded as promising scaffolds for developing anticancer agents.	[Malarz, Katarzyna; Kuczak, Michal; Mrozek-Wilczkiewicz, Anna] Univ Silesia Katowice, A Chelkowski Inst Phys, 75 Pulku Piechoty 1a, PL-41500 Chorzow, Poland; [Malarz, Katarzyna; Kuczak, Michal; Mrozek-Wilczkiewicz, Anna] Univ Silesia Katowice, Silesian Ctr Educ & Interdisciplinary Res, 75 Pulku Piechoty 1a, PL-41500 Chorzow, Poland; [Mularski, Jacek; Kuczak, Michal; Musiol, Robert] Univ Silesia Katowice, Inst Chem, 75 Pulku Piechoty 1a, PL-41500 Chorzow, Poland		Malarz, K (corresponding author), Univ Silesia Katowice, A Chelkowski Inst Phys, 75 Pulku Piechoty 1a, PL-41500 Chorzow, Poland.; Malarz, K (corresponding author), Univ Silesia Katowice, Silesian Ctr Educ & Interdisciplinary Res, 75 Pulku Piechoty 1a, PL-41500 Chorzow, Poland.; Musiol, R (corresponding author), Univ Silesia Katowice, Inst Chem, 75 Pulku Piechoty 1a, PL-41500 Chorzow, Poland.	katarzyna.malarz@us.edu.pl; jacek.mularski@us.edu.pl; mkuczak@us.edu.pl; anna.mrozek-wilczkiewicz@us.edu.pl; robert.musiol@us.edu.pl		K, Michal/0000-0002-7577-3011; Mularski, Jacek/0000-0002-1502-0421; Musiol, Robert/0000-0002-6219-7369; Malarz, Katarzyna/0000-0003-4283-3126	National Science CentreNational Science Centre, Poland [2019/35/B/NZ5/04208]	This work was financed by the National Science Centre grant 2019/35/B/NZ5/04208 (K.M.).	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J	Olsen, I; Yilmaz, O				Olsen, Ingar; Yilmaz, Ozlem			Possible role of Porphyromonas gingivalis in orodigestive cancers	JOURNAL OF ORAL MICROBIOLOGY			English	Review						Porphyromonas gingivalis; orodigestive cancers; oral cavity; esophagus; colon; pancreas; precancerous lesions; experimental models; direct relationship	SQUAMOUS-CELL CARCINOMA; PEPTIDYLARGININE DEIMINASE TYPE-4; NUCLEOSIDE-DIPHOSPHATE-KINASE; ORAL-CANCER; PERIODONTAL-DISEASE; EPITHELIAL-CELLS; POLYMICROBIAL SYNERGY; GENE-EXPRESSION; NECK-CANCER; RISK	There is increasing evidence for an association between periodontitis/tooth loss and oral, gastrointestinal, and pancreatic cancers. Periodontal disease, which is characterized by chronic inflammation and microbial dysbiosis, is a significant risk factor for orodigestive carcinogenesis. Porphyromonas gingivalis is proposed as a keystone pathogen in chronic periodontitis causing both dysbiosis and discordant immune response. The present review focuses on the growing recognition of a relationship between P. gingivalis and orodigestive cancers. Porphyromonas gingivalis has been recovered in abundance from oral squamous cell carcinoma (OSCC). Recently established tumorigenesis models have indicated a direct relationship between P. gingivalis and carcinogenesis. The bacterium upregulates specific receptors on OSCC cells and keratinocytes, induces epithelial-to-mesenchymal (EMT) transition of normal oral epithelial cells and activates metalloproteinase-9 and interleukin-8 in cultures of the carcinoma cells. In addition, P. gingivalis accelerates cell cycling and suppresses apoptosis in cultures of primary oral epithelial cells. In oral cancer cells, the cell cycle is arrested and there is no effect on apoptosis, but macro autophagy is increased. Porphyromonas gingivalis promotes distant metastasis and chemoresistance to anti-cancer agents and accelerates proliferation of oral tumor cells by affecting gene expression of defensins, by peptidyl-arginine deiminase and noncanonical activation of beta-catenin. The pathogen also converts ethanol to the carcinogenic intermediate acetaldehyde. In addition, P. gingivalis can be implicated in precancerous gastric and colon lesions, esophageal squamous cell carcinoma, head and neck (larynx, throat, lip, mouth and salivary glands) carcinoma, and pancreatic cancer. The fact that distant organs can be involved clearly emphasizes that P. gingivalis has systemic tumorigenic effects in addition to the local effects in its native territory, the oral cavity. Although coinfection with other bacteria, viruses, and fungi occurs in periodontitis, P. gingivalis relates to cancer even in absence of periodontitis. Thus, there may be a direct relationship between P. gingivalis and orodigestive cancers.	[Olsen, Ingar] Univ Oslo, Fac Dent, Dept Oral Biol, POB 1052 Blindern, N-0316 Oslo, Norway; [Yilmaz, Ozlem] Med Univ South Carolina, Dept Oral Hlth Sci, Charleston, SC 29425 USA		Olsen, I (corresponding author), Univ Oslo, Fac Dent, Dept Oral Biol, POB 1052 Blindern, N-0316 Oslo, Norway.	ingaro@odont.uio.no	Yilmaz, Ozlem/ABG-5367-2021	Yilmaz, Ozlem/0000-0003-3487-7217	NIDCRUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [R01DE016593]; NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [R01DE016593] Funding Source: NIH RePORTER	This work was supported by the NIDCR [grant number R01DE016593 to OY].	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Oral Microbiology	JAN 1	2019	11	1								10.1080/20002297.2018.1563410			12	Microbiology	Science Citation Index Expanded (SCI-EXPANDED)	Microbiology	HH1OL	WOS:000455489400001	30671195	Green Published, gold			2022-04-25	
J	Hou, XY; Yang, CL; Zhang, LJ; Hu, TT; Sun, D; Cao, H; Yang, F; Guo, G; Gong, CY; Zhang, XN; Tong, AP; Li, R; Zheng, Y				Hou, Xueyan; Yang, Chengli; Zhang, Lijing; Hu, Tingting; Sun, Dan; Cao, Hua; Yang, Fan; Guo, Gang; Gong, Changyang; Zhang, Xiaoning; Tong, Aiping; Li, Rui; Zheng, Yu			Killing colon cancer cells through PCD pathways by a novel hyaluronic acid-modified shell-core nanoparticle loaded with RIP3 in combination with chloroquine	BIOMATERIALS			English	Article						Hyaluronic acid-modified shell-core; nanoparticle; mRIP3; Chloroquine; Necroptosis; Autophagy; Lysosomal membrane permeabilization; (LMP)	POLYMER HYBRID NANOPARTICLES; NEGATIVE BREAST-CANCER; PLGA NANOPARTICLES; GENE DELIVERY; AUTOPHAGY; TUMOR; APOPTOSIS; DEATH; DRUG; INHIBITION	Due to extensive apoptosis defects and multidrug resistance, there is great interest regarding nonapoptotic programmed cell death (PCD) pathways, such as lysosomal-mediated programmed cell death (LM-PCD), necroptosis and autophagy. Because there is an intricate effector network among these PCD pathways, it is expected that they may act synergistically in cancer therapy. In this study, chloroquine (CQ) was found to significantly upregulate receptor-interacting protein kinase 3 (RIP3) expression, and RIP3 were involved in CQ-related autophagy. Overexpressed-eGFP-RIP3 co-localized with the selective autophagy receptor p62. mRIP3 overexpression in combination with CQ markedly increased the inhibition rate relative to that observed in the CQ-treatment group. Several experiments, including Hoechst staining, transmission electron microscopy (TEM) observation, the high-mobility group box 1 (HMGB1) release assay, Annexin V/PI staining and immunoblotting of proteins included in PCD pathways, verified that mRIP3 overexpression in combination with CQ induced lysosomal membrane permeabilization (LMP) and necroptosis of cancer cells, leading to cancer cell death. For tumor-targeted delivery, hyaluronic acid (HA)-modified, lipid-coated PLGA nanoparticles loaded with mRlP3-pDNA were prepared and characterized using a particle sizer, differential scanning calorimetry (DSC) and TEM. The nanoparticles exhibited ideal biocompatibility and good tumor-targeting efficiency, and the tumor inhibition rate of HA-Lip-PEI-mRIP3-PLGA-NPs CQ was 80.2% in the CT26 mouse model. In this study, we attempted to treat tumors by inducing several alternative PCD pathways to shed light on the combination therapy of alternative PCD inducers. (C) 2017 Elsevier Ltd. All rights reserved.	[Hou, Xueyan; Hu, Tingting; Cao, Hua; Guo, Gang; Gong, Changyang; Tong, Aiping; Li, Rui; Zheng, Yu] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Collaborat Innovat Ctr Biotherapy, 17,Sect 3,Ren Min Nan Rd, Chengdu 610041, Sichuan, Peoples R China; [Yang, Chengli] Zunyi Med Univ, Dept Clin Pharm, Sch Pharm, 6 Xuefu Xi Rd, Zunyi 563006, Guizhou, Peoples R China; [Zhang, Lijing] Zhengzhou Univ, Med Res Ctr, Affiliated Hosp 1, 1 Jianshe East Rd, Zhengzhou 450052, Henan, Peoples R China; [Sun, Dan] Sichuan Univ, Coll Life Sci, Chengdu 610041, Sichuan, Peoples R China; [Yang, Fan] Sichuan Univ, West China Univ Hosp 2, Dept Gynecol, Chengdu 610041, Peoples R China; [Zhang, Xiaoning] Tsinghua Univ, Sch Med, Lab Pharmaceut, 30 Shuangqing Rd, Beijing 100084, Peoples R China		Zheng, Y (corresponding author), Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Collaborat Innovat Ctr Biotherapy, 17,Sect 3,Ren Min Nan Rd, Chengdu 610041, Sichuan, Peoples R China.	zhengyu82@scu.edu.cn	孙, 丹/AAJ-6568-2020		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81001012]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2014T70877, 2013M542421]	The mRIP3-pDNA is a gift from Dr. Jiahuai Han (Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China). This work was supported by the National Natural Science Foundation of China (81001012), the China Postdoctoral Science Foundation (2014T70877, 2013M542421).	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Materials Science, Biomaterials	Science Citation Index Expanded (SCI-EXPANDED)	Engineering; Materials Science	EN4CS	WOS:000395956000016	28199887				2022-04-25	
J	Hsieh, YY; Chou, CJ; Lo, HL; Yang, PM				Hsieh, Y-Y; Chou, C-J; Lo, H-L; Yang, P-M			Repositioning of a cyclin-dependent kinase inhibitor GW8510 as a ribonucleotide reductase M2 inhibitor to treat human colorectal cancer	CELL DEATH DISCOVERY			English	Article								Colorectal cancer (CRC) is the second leading cause of cancer-related death in males and females in the world. It is of immediate importance to develop novel therapeutics. Human ribonucleotide reductase (RRM1/RRM2) has an essential role in converting ribonucleoside diphosphate to 2'-deoxyribonucleoside diphosphate to maintain the homeostasis of nucleotide pools. RRM2 is a prognostic biomarker and predicts poor survival of CRC. In addition, increased RRM2 activity is associated with malignant transformation and tumor cell growth. Bioinformatics analyses show that RRM2 was overexpressed in CRC and might be an attractive target for treating CRC. Therefore, we attempted to search novel RRM2 inhibitors by using a gene expression signature-based approach, connectivity MAP (CMAP). The result predicted GW8510, a cyclin-dependent kinase inhibitor, as a potential RRM2 inhibitor. Western blot analysis indicated that GW8510 inhibited RRM2 expression through promoting its proteasomal degradation. In addition, GW8510 induced autophagic cell death. In addition, the sensitivities of CRC cells to GW8510 were associated with the levels of RRM2 and endogenous autophagic flux. Taken together, our study indicates that GW8510 could be a potential anti-CRC agent through targeting RRM2.	[Hsieh, Y-Y; Chou, C-J; Lo, H-L; Yang, P-M] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Biol & Drug Discovery, Taipei, Taiwan; [Hsieh, Y-Y; Chou, C-J; Lo, H-L; Yang, P-M] Acad Sinica, Taipei, Taiwan; [Hsieh, Y-Y] Taipei Meidcal Univ, Shuang Ho Hosp, Div Hematol & Oncol, Taipei, Taiwan; [Chou, C-J; Lo, H-L; Yang, P-M] Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Canc Biol & Drug Discovery, Taipei, Taiwan		Yang, PM (corresponding author), Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Biol & Drug Discovery, Taipei, Taiwan.; Yang, PM (corresponding author), Acad Sinica, Taipei, Taiwan.; Yang, PM (corresponding author), Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Canc Biol & Drug Discovery, Taipei, Taiwan.	yangpm@tmu.edu.tw	Yang, Pei-Ming/G-3763-2014	Yang, Pei-Ming/0000-0002-4004-2518	Taiwan's Ministry of Science and Technology [MOST103-2632-B-038-001, MOST104-2320-B-038-005]; Taipei Medical University-Shuang Ho Hospital [104TMU-SHH-03]; Research Team of Prevention and Therapy of Colorectal Cancer at Taipei Medical University [TMU-T104-01]; Comprehensive Cancer Center of Taipei Medical University - Health and welfare surcharge of tobacco products [MOHW105-TDU-B-212-134001]	This work was supported by research grants from Taiwan's Ministry of Science and Technology (MOST103-2632-B-038-001 and MOST104-2320-B-038-005), Taipei Medical University-Shuang Ho Hospital (104TMU-SHH-03), Research Team of Prevention and Therapy of Colorectal Cancer at Taipei Medical University (TMU-T104-01), and Comprehensive Cancer Center of Taipei Medical University (MOHW105-TDU-B-212-134001) funded by the Health and welfare surcharge of tobacco products.	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J	Li, YJ; Chen, YY; Huang, HY; Shi, MM; Yang, WP; Kuang, J; Yan, JQ				Li, Yongjian; Chen, Yunyang; Huang, Haiyan; Shi, Minmin; Yang, Weiping; Kuang, Jie; Yan, Jiqi			Autophagy mediated by endoplasmic reticulum stress enhances the caffeine-induced apoptosis of hepatic stellate cells	INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE			English	Article						caffeine; endoplasmic reticulum stress; autophagy; inositol-requiring enzyme-1 alpha; liver fibrosis	UNFOLDED-PROTEIN RESPONSE; PROMOTES TUMOR-GROWTH; LIVER FIBROSIS; MOLECULAR-MECHANISMS; COFFEE CONSUMPTION; COLORECTAL-CANCER; ACTIVATION; DISEASE; EXPRESSION; SORAFENIB	Caffeine has been identified to have beneficial effects against chronic liver diseases, particularly liver fibrosis. Many studies have reported that caffeine ameliorates liver fibrosis by directly inducing hepatic stellate cell (HSC) apoptosis; however, the molecular mechanisms involved in this process remain unclear. The presents study aimed to detect the underlying mechanisms by which caffeine mediates HSC apoptosis and eliminates activated HSCs. For this purpose, the LX-2 cell line was applied in this study and the cells were exposed to various concentrations of caffeine for the indicated times. The effects of caffeine on cell viability and apoptosis were assessed by Cell Counting Kit-8 assay and flow cytometry, respectively. Autophagy and endoplasmic reticulum (ER) stress were explored by morphological assessment and western blotting. In the present study, caffeine was found to inhibit the viability and increase the apoptosis of the LX-2 cells in dose-and time-dependent manners. ER stress was stimulated by caffeine as demonstrated by increased levels of GRP78/Bip, CHOP and inositol-requiring enzyme 1 (IRE1)-alpha as well as many enlarged ERs detected by electron microscopy. Caffeine induced autophagy as shown by increased p62 and LC3. accumulation and the number of GFP/RFP-LC3 puncta and autophagosomes/autolysosomes. Moreover, IRE1-alpha knockdown decreased the level of autophagic flux, and inhibition of autophagy protected LX-2 cells from apoptotic death. In conclusion, our study showed that the caffeine-enhanced autophagic flux in HSCs was stimulated by ER stress via the IRE1-alpha signaling pathway, which further weakened HSC viability via the induction of apoptosis. These findings provide new insight into the mechanism of caffeine's anti-fibrotic effects.	[Li, Yongjian; Chen, Yunyang; Huang, Haiyan; Yang, Weiping; Kuang, Jie; Yan, Jiqi] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Gen Surg, 197 Ruijin Er Rd, Shanghai 200025, Peoples R China; [Li, Yongjian; Chen, Yunyang; Shi, Minmin; Yang, Weiping; Kuang, Jie; Yan, Jiqi] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Shanghai Inst Digest Surg, Shanghai 200025, Peoples R China; [Chen, Yunyang] Jiangmen Cent Hosp, Dept Hepatobiliary Surg, Jiangmen 529030, Guangdong, Peoples R China		Kuang, J; Yan, JQ (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Gen Surg, 197 Ruijin Er Rd, Shanghai 200025, Peoples R China.	kuangjie823@msn.com; yanjiqi@sohu.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81070358]	This study was supported by the National Natural Science Foundation of China (no. 81070358), (http://www.nsfc.gov.cn) to JQY.	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J. Mol. Med.	NOV	2017	40	5					1405	1414		10.3892/ijmm.2017.3145			10	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	FK3PS	WOS:000413398800011	28949381	Green Submitted, hybrid, Green Published			2022-04-25	
J	Gueraud, F; Atalay, M; Bresgen, N; Cipak, A; Eckl, PM; Huc, L; Jouanin, I; Siems, W; Uchida, K				Gueraud, F.; Atalay, M.; Bresgen, N.; Cipak, A.; Eckl, P. M.; Huc, L.; Jouanin, I.; Siems, W.; Uchida, K.			Chemistry and biochemistry of lipid peroxidation products	FREE RADICAL RESEARCH			English	Review						Lipid peroxidation; alkenals; 4-hydroxy-2-nonenal; glutathione; apoptosis; adducts; volatile aldehydes	LOW-DENSITY-LIPOPROTEIN; POLYUNSATURATED FATTY-ACIDS; GLUTATHIONE-S-TRANSFERASE; PROTEIN-DISULFIDE-ISOMERASE; PIGMENT EPITHELIAL-CELLS; HEADSPACE GAS-CHROMATOGRAPHY; AMYLOID-BETA-PEPTIDE; HEAT-SHOCK PROTEINS; DNA-DAMAGE RESPONSE; COLON-CANCER CELLS	Oxidative stress and resulting lipid peroxidation is involved in various and numerous pathological states including inflammation, atherosclerosis, neurodegenerative diseases and cancer. This review is focused on recent advances concerning the formation, metabolism and reactivity towards macromolecules of lipid peroxidation breakdown products, some of which being considered as 'second messengers' of oxidative stress. This review relates also new advances regarding apoptosis induction, survival/proliferation processes and autophagy regulated by 4-hydroxynonenal, a major product of omega-6 fatty acid peroxidation, in relationship with detoxication mechanisms. The use of these lipid peroxidation products as oxidative stress/lipid peroxidation biomarkers is also addressed.	[Gueraud, F.; Huc, L.; Jouanin, I.] INRA, UMR1089 Xenobiot, F-31027 Toulouse 3, France; [Atalay, M.] Univ Eastern Finland, Inst Biomed, Kuopio, Finland; [Bresgen, N.; Eckl, P. 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Res.	OCT	2010	44	10			SI		1098	1124		10.3109/10715762.2010.498477			27	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	654BP	WOS:000282143400002	20836659	Green Published			2022-04-25	
J	Gijon, M; Metheringham, RL; Toss, MS; Paston, SJ; Durrant, LG				Gijon, Mohamed; Metheringham, Rachael L.; Toss, Michael S.; Paston, Samantha J.; Durrant, Lindy G.			The Clinical and Prognostic Significance of Protein Arginine Deiminases 2 and 4 in Colorectal Cancer	PATHOBIOLOGY			English	Article; Early Access						Protein arginine deiminase 2; Protein arginine deiminase 4; Citrullination; Colorectal cancer; Immunohistochemistry	MHC CLASS-I; PEPTIDYLARGININE DEIMINASE; CITRULLINATED VIMENTIN; RHEUMATOID-ARTHRITIS; HISTONE DEIMINATION; BETA-CATENIN; COLON-CANCER; EXPRESSION; CELLS; AUTOPHAGY	Introduction: Protein arginine deiminases (PADIs) are a family of enzymes that catalyse the post-translational modification of proteins. Association between PADI expression and clinicopathology, protein expression, and outcome was determined. Methods: PADI2 and PADI4 expression was assessed immunohistochemically in a cohort of colorectal cancer (CRC) patients. Results: CRC tissues expressed variable levels of PADI2 which was mainly localised in the cytoplasm and correlated with patient survival (p = 0.005); high expression increased survival time from 43.5 to 67.6 months. Expression of cytoplasmic PADI2 correlated with the expression of nuclear beta catenin, PADI4, and alpha-enolase. In contrast, expression of nuclear PADI2 correlated with a decrease in survival (p = 0.010), with high expression decreasing survival from 76.4 to 42.9 months. CRC tissues expressed variable levels of PADI4 in both the nucleus and cytoplasm. Expression of cytoplasmic PADI4 correlated with survival (p = 0.001) with high expression increasing survival time from 48.1 to 71.8 months. Expression of cytoplasmic PADI4 correlated with expression of nuclear beta catenin, alpha-enolase (p <= 0.0001, p = 0.002), and the apoptotic related protein, Bcl-2. Expression of nuclear PADI4 also correlated with survival (p = 0.011), with high expression of nuclear PADI4 increasing survival time from 55.4 to 74 months. Expression of nuclear PADI4 correlated with p53, alpha-enolase, and Bcl-2. Multivariate analysis showed that TNM stage, cytoplasmic PADI2, and PADI4 remained independent prognostic factors in CRC. Both PADI2 and PADI4 are good prognostic factors in CRC. Conclusion: High expression of cytoplasmic PADI2, PADI4, and nuclear PADI4 were associated with an increase in overall survival.	[Gijon, Mohamed; Metheringham, Rachael L.; Paston, Samantha J.; Durrant, Lindy G.] Scancell Ltd, Biodiscovery Inst, Univ Pk, Nottingham, England; [Durrant, Lindy G.] Univ Nottingham, Biodiscovery Inst, Div Canc & Stem Cells, Univ Pk, Nottingham, England; [Toss, Michael S.] Univ Nottingham, Nottingham City Hosp, Nottingham Breast Canc Res Ctr, Sch Med,Div Canc & Stem Cells, Nottingham, England		Durrant, LG (corresponding author), Scancell Ltd, Biodiscovery Inst, Univ Pk, Nottingham, England.; Durrant, LG (corresponding author), Univ Nottingham, Biodiscovery Inst, Div Canc & Stem Cells, Univ Pk, Nottingham, England.	lindy.durrant@nottingham.ac.uk		Gijon, Mohamed/0000-0002-2444-0727	Scancell Ltd.	This work was funded by Scancell Ltd.	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S	Baghy, K; Reszegi, A; Tatrai, P; Kovalszky, I		Birbrair, A		Baghy, Kornelia; Reszegi, Andrea; Tatrai, Peter; Kovalszky, Ilona			Decorin in the Tumor Microenvironment	TUMOR MICROENVIRONMENT: EXTRACELLULAR MATRIX COMPONENTS - PT B	Advances in Experimental Medicine and Biology		English	Article; Book Chapter						Decorin; Extracellular matrix; Receptor tyrosine kinase; Autophagy; Mitophagy; Inflammation; SLRP; Tumor; Stroma; EGFR; Met; Angiogenesis; Cell cycle; Signaling; Growth factor	EPIDERMAL-GROWTH-FACTOR; LEUCINE-RICH PROTEOGLYCANS; BREAST-CARCINOMA CELLS; HUMAN-COLON CARCINOMA; IMPRINTED GENE PEG3; FACTOR-I RECEPTOR; EXTRACELLULAR-MATRIX; CANCER GROWTH; FACTOR-BETA; COLLAGEN FIBRILLOGENESIS	The tumor microenvironment plays a determining role in cancer development through a plethora of interactions between the extracellular matrix and tumor cells. Decorin is a prototype member of the SLRP family found in a variety of tissues and is expressed in the stroma of various forms of cancer. Decorin has gained recognition for its essential roles in inflammation, fibrotic disorders, and cancer, and due to its antitumor properties, it has been proposed to act as a "guardian from the matrix." Initially identified as a natural inhibitor of transforming growth factor-beta, soluble decorin is emerging as a pan-RTK inhibitor targeting a multitude of RTKs, including EGFR, Met, IGF-IR, VEGFR2, and PDGFR. Besides initiating signaling, decorin/RTK interaction can induce caveosomal internalization and receptor degradation. Decorin also triggers cell cycle arrest and apoptosis and evokes antimetastatic and antiangiogenic processes. In addition, as a novel regulatory mechanism, decorin was shown to induce conserved catabolic processes, such as endothelial cell autophagy and tumor cell mitophagy. Therefore, decorin is a promising candidate for combatting cancer, especially the cancer types heavily dependent on RTK signaling.	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Zhang W, 2018, ONCOTARGET, V9, P5480, DOI 10.18632/oncotarget.23869; Zhu J, 2007, J BIOL CHEM, V282, P25852, DOI 10.1074/jbc.M704146200; Zhu JX, 2005, J BIOL CHEM, V280, P32468, DOI 10.1074/jbc.M503833200; Zwirner NW, 2010, CURR PHARM DESIGN, V16, P255, DOI 10.2174/138161210790170175	188	7	7	2	2	SPRINGER INTERNATIONAL PUBLISHING AG	CHAM	GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND	0065-2598	2214-8019	978-3-030-48457-6; 978-3-030-48456-9	ADV EXP MED BIOL	Adv.Exp.Med.Biol.		2020	1272						17	38		10.1007/978-3-030-48457-6_2	10.1007/ 978-3-030-48457-6		22	Biochemistry & Molecular Biology; Oncology	Book Citation Index – Science (BKCI-S); Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Oncology	BP9DW	WOS:000569017500003	32845500				2022-04-25	
J	Chiang, JH; Tsai, FJ; Hsu, YM; Yin, MC; Chiu, HY; Yang, JS				Chiang, Jo-Hua; Tsai, Fuu-Jen; Hsu, Yuan-Man; Yin, Mei-Chin; Chiu, Hong-Yi; Yang, Jai-Sing			Sensitivity of allyl isothiocyanate to induce apoptosis via ER stress and the mitochondrial pathway upon ROS production in colorectal adenocarcinoma cells	ONCOLOGY REPORTS			English	Article						allyl isothiocyanate; colon cancer cells; apoptosis; ER stress; mitochondria; ROS production	ENDOPLASMIC-RETICULUM STRESS; PHASE ARREST; IN-VITRO; CANCER; PROLIFERATION; INHIBITION; ANGIOGENESIS; DYSFUNCTION; METASTASIS; AUTOPHAGY	Allyl isothiocyanate (AITC), a bioactive phytochemical compound that is a constituent of dietary cruciferous vegetables, possesses promising chemopreventive and anticancer effects. However, reports of AITC exerting antitumor effects on apoptosis induction of colorectal cancer (CRC) cells in vitro are not well elucidated. The present study focused on the functional mechanism of the endoplasmic reticulum (ER) stress-based apoptotic machinery induced by AITC in human colorectal cancer HT-29 cells. Our results indicated that AITC decreased cell growth and number, reduced viability, and facilitated morphological changes of apoptotic cell death. DNA analysis by flow cytometry showed G2/M phase arrest, and alterations in the modulated protein levels caused by AITC were detected via western blot analysis. AITC also triggered vital intrinsic apoptotic factors (caspase-9/caspase-3 activity), disrupted mitochondrial membrane potential, and stimulated mitochondrial-related apoptotic molecules (e.g., cytochrome c, apoptotic protease activating factor 1, apoptosis-inducing factor, and endonuclease G). Additionally, AITC prompted induced cytosolic Ca2+ release and Ca2+-dependent ER stress-related signals, such as calpain 1, activating transcription factor 6 alpha, glucose-regulated proteins 78 and 94, growth arrest- and DNA damage-inducible protein 153 (GADD153), and caspase-4. The level of reactive oxygen species (ROS) production was found to induce the hallmark of ER stress GADD153, proapoptotic marker caspase-3, and calpain activity after AITC treatment. Our findings showed for the first time that AITC induced G2/M phase arrest and apoptotic death via ROS-based ER stress and the intrinsic pathway (mitochondrial-dependent) in HT-29 cells. Overall, AITC may exert an epigenetic effect and is a potential bioactive compound for CRC treatment.	[Chiang, Jo-Hua] Chung Jen Jr Coll Nursing Hlth Sci & Management, Dept Nursing, Chiayi 62241, Taiwan; [Tsai, Fuu-Jen] China Med Univ Hosp, Dept Med Res, Human Genet Ctr, Taichung 40447, Taiwan; [Tsai, Fuu-Jen] China Med Univ Hosp, Dept Med Genet, Taichung 40447, Taiwan; [Tsai, Fuu-Jen] China Med Univ, Sch Chinese Med, Taichung 40402, Taiwan; [Hsu, Yuan-Man] China Med Univ, Dept Biol Sci & Technol, Taichung 40402, Taiwan; [Yin, Mei-Chin] Asia Univ, Dept Food Nutr & Hlth Biotechnol, Taichung 41354, Taiwan; [Chiu, Hong-Yi] Buddhist Tzu Chi Med Fdn, Hualien Tzu Chi Hosp, Dept Pharm, Sec 3,707 Chung Yang Rd, Hualien 97002, Taiwan; [Chiu, Hong-Yi] Tzu Chi Univ, Sch Med, Master & PhD Program Pharmacol & Toxicol, Hualien 97004, Taiwan; [Chiu, Hong-Yi] Tzu Chi Univ Sci & Technol, Gen Educ Ctr, Hualien 97005, Taiwan; [Yang, Jai-Sing] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 40442, Taiwan		Chiu, HY (corresponding author), Buddhist Tzu Chi Med Fdn, Hualien Tzu Chi Hosp, Dept Pharm, Sec 3,707 Chung Yang Rd, Hualien 97002, Taiwan.; Yang, JS (corresponding author), China Med Univ, China Med Univ Hosp, Dept Med Res, 2 Yude Rd, Taichung 40447, Taiwan.	hychiu@tzuchi.com.tw; jaisingyang@gmail.com	Hsu, Yuan-Man/K-7074-2015	Hsu, Yuan-Man/0000-0002-4575-7475	Chung-Jen Junior College of Nursing, Health Sciences and Management [105015, 106-003]; Hualien Tzu Chi Hospital [TCRD107-55]; China Medical University Hospital [DMR-108-122]	This work was financially supported by Chung-Jen Junior College of Nursing, Health Sciences and Management (grants nos. 105015 and 106-003) and in part by Hualien Tzu Chi Hospital (grant no. TCRD107-55) and China Medical University Hospital (grant no. DMR-108-122).	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Rep.	OCT	2020	44	4					1415	1424		10.3892/or.2020.7700			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	NO3CL	WOS:000569361800012	32700751	Green Published, hybrid			2022-04-25	
J	Schonewolf, CA; Mehta, M; Schiff, D; Wu, H; Haffty, BG; Karantza, V; Jabbour, SK				Schonewolf, Caitlin A.; Mehta, Monal; Schiff, Devora; Wu, Hao; Haffty, Bruce G.; Karantza, Vassiliki; Jabbour, Salma K.			Autophagy inhibition by chloroquine sensitizes HT-29 colorectal cancer cells to concurrent chemoradiation	WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY			English	Article						Autophagy; Chloroquine; Radiosensitization; Colorectal cancer	HIF-1	AIM: To investigate whether the inhibition of autophagy by chloroquine (CQ) sensitizes rectal tumors to radiation therapy (RT) or concurrent chemoradiation (chemoRT). METHODS: In vitro, HCT-116 and HT-29 colorectal cancer (CRC) cell lines were treated as following: (1) PBS; (2) CQ; (3) 5-fluorouracil (5-FU); (4) RT; (5) CQ and RT; (6) 5-FU and RT; (7) CQ and 5-FU; and (8) 5-FU and CQ and RT. Each group was then exposed to various doses of radiation (0-8 Gy) depending on the experiment. Cell viability and proliferative capacity were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays. Clonogenic survival curves were constructed and compared across treatment groups. Autophagy status was determined by assessing the LC3-II to LC3-I ratio on western blot analysis, autophagosome formation on electron microscopy and identification of a perinuclear punctate pattern with GFP-labeled LC3 on fluorescence microscopy. Cell cycle arrest and cell death were evaluated by FACS and Annexin. analysis. All experiments were performed in triplicate and statistical analysis was performed by the student's t test to compare means between treatment groups. RESULTS: RT (2-8 Gy) induced autophagy in HCT-116 and HT-29 CRC cell lines at 4 and 6 h post-radiation, respectively, as measured by increasing LC3-II to LC3-I ratio on western blot. Additionally, electron microscopy demonstrated autophagy induction in HT-29 cells 24 h following irradiation at a dose of 8 Gy. Drug treatment with 5-FU (25 mu mol/L) induced autophagy and the combination of 5-FU and RT demonstrated synergism in autophagy induction. CQ (10 mu mol/L) alone and in combination with RT effectively inhibited autophagy and sensitized both HCT-116 and HT-29 cells to treatment with radiation (8 Gy; P < 0.001 and 0.00001, respectively). Significant decrease in clonogenic survival was seen only in the HT-29 cell line, when CQ was combined with RT at doses of 2 and 8 Gy (P < 0.5 and P = 0.05, respectively). There were no differences in cell cycle progression or Annexin V staining upon CQ addition to RT. CONCLUSION: Autophagy inhibition by CQ increases CRC cell sensitivity to concurrent treatment with 5-FU and RT in vitro, suggesting that addition of CQ to chemoRT improves CRC treatment response. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.	[Schonewolf, Caitlin A.; Mehta, Monal; Schiff, Devora; Wu, Hao; Haffty, Bruce G.; Jabbour, Salma K.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Dept Radiat Oncol, 195 Little Albany St, New Brunswick, NJ 08903 USA; [Karantza, Vassiliki] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Dept Med, New Brunswick, NJ 08903 USA		Jabbour, SK (corresponding author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Dept Radiat Oncol, 195 Little Albany St, New Brunswick, NJ 08903 USA.	jabbousk@umdnj.edu					Amaravadi RK, 2011, CLIN CANCER RES, V17, P654, DOI 10.1158/1078-0432.CCR-10-2634; Apel A, 2008, CANCER RES, V68, P1485, DOI 10.1158/0008-5472.CAN-07-0562; Capirci C, 2008, INT J RADIAT ONCOL, V72, P99, DOI 10.1016/j.ijrobp.2007.12.019; Dewhirst MW, 2007, CANCER RES, V67, P854, DOI 10.1158/0008-5472.CAN-06-4744; Guo JY, 2011, GENE DEV, V25, P460, DOI 10.1101/gad.2016311; Karantza-Wadsworth V, 2007, GENE DEV, V21, P1621, DOI 10.1101/gad.1565707; Kimmelman AC, 2011, GENE DEV, V25, P1999, DOI 10.1101/gad.17558811; Li J, 2010, EUR J CANCER, V46, P1900, DOI 10.1016/j.ejca.2010.02.021; Li J, 2009, ANN SURG ONCOL, V16, P761, DOI 10.1245/s10434-008-0260-0; Livesey KM, 2012, AUTOPHAGY, V8, P846, DOI 10.4161/auto.19891; Maas M, 2010, LANCET ONCOL, V11, P835, DOI 10.1016/S1470-2045(10)70172-8; Moeller BJ, 2005, CANCER CELL, V8, P99, DOI 10.1016/j.ccr.2005.06.016; Moeller BJ, 2004, CANCER CELL, V5, P429, DOI 10.1016/S1535-6108(04)00115-1; Morselli E, 2011, CELL CYCLE, V10, P2763, DOI 10.4161/cc.10.16.16868; Paillas S, 2012, AUTOPHAGY, V8, P1098, DOI [10.1461/auto.20268, DOI 10.1461/AUTO.20268]; Sasaki K, 2010, BMC CANCER, V10, DOI 10.1186/1471-2407-10-370; Siegel R, 2013, CA-CANCER J CLIN, V63, P11, DOI 10.3322/caac.21166; Sui XB, 2011, AUTOPHAGY, V7, P565, DOI 10.4161/auto.7.6.14073	18	49	52	0	7	BAISHIDENG PUBLISHING GROUP INC	PLEASANTON	8226 REGENCY DR, PLEASANTON, CA 94588 USA	1948-5204			WORLD J GASTRO ONCOL	World J. Gastrointest. Oncol.	MAR 15	2014	6	3					74	82		10.4251/wjgo.v6.i3.74			9	Oncology; Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Gastroenterology & Hepatology	V9A3O	WOS:000422130700003	24653797	Green Published, hybrid, Green Submitted			2022-04-25	
J	Li, T; Zhang, SY; Chen, FS; Hu, J; Yuan, S; Li, CR; Wang, XT; Zhang, WH; Tang, RW				Li, Tian; Zhang, Shiyi; Chen, Fengsong; Hu, Jun; Yuan, Shuai; Li, Chaoran; Wang, Xiaoting; Zhang, Weihong; Tang, Runwei			Formononetin ameliorates the drug resistance of Taxol resistant triple negative breast cancer by inhibiting autophagy	AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH			English	Article						Formononetin; Taxol; triple negative breast cancer; autophagy; miR-199a-3p	MECHANISMS; INVASION; GROWTH	Characterized by autophagy-associated protein disorders, autophagy participates in Taxol resistance in triple negative breast cancer (TNBC). As an evolutionarily conserved serine/threonine protein kinase with complex signaling pathway, mammalian target of rapamycin (mTOR) can regulate various cellular functions by phosphorylation of its downstream target proteins after activation. A large number of references have demonstrated that mTOR signaling pathway is related to autophagy and apoptosis. Formononetin (FMNT) has anticancer properties against breast, prostate and colon cancers. This study aimed to explore the regulatory effect of FMNT/miR-199a-3p/mTOR pathway on Taxol resistance and autophagy in breast cancer (BC). MiR-199a-3p, mTOR, LC3 and other autophagy related proteins were detected in Taxol sensitive and Taxol resistant TNBC cell lines, which were MDA-MB-231 and MDA-MB-231/Taxol, respectively. Cell viability and toxicity were determined by CCK-8 and MTT assay, respectively. The therapeutic effect of FMNT was evaluated in xenotransplantation model of nude mice. MiR-199a-3p was more highly expressed in MDA-MB-231/Taxol than in MDA-MB-231, while mTOR and p-mTOR decreased in MDA-MB-231/Taxol in comparison with MDA-MB-231, and autophagy activation and drug resistance were enhanced. In MDAMB-231/Taxol cell line, the role of FMNT was verified to inhibit high miR-199a-3p expression. In addition, the combination therapy of FMNT and Taxol was found to be more effective in inhibiting autophagy and drug resistance. Moreover, mTOR was the target of miR-199a-3p, which was confirmed by dual luciferase reporter (DLR) gene assay. Oral administration of FMNT reduced tumor volume after MDA-MB-231/Taxol injection in vivo. Moreover, oral administration of FMNT and Taxol suppressed autophagy and Taxol resistance by restoring mTOR protein level to that of the parent MDA-MB-231, suggesting that miR-199a-3p can severe as a new target to overcome Taxol resistance in TNBC.	[Li, Tian; Yuan, Shuai; Li, Chaoran; Wang, Xiaoting; Zhang, Weihong; Tang, Runwei] Shanghai Univ Tradit Chinese Med, Breast Surg Dept, Baoshan Branch, Shanghai 201900, Peoples R China; [Zhang, Shiyi] Guangdong Med Univ, Sch Clin Med 2, Dongguan 523000, Peoples R China; [Chen, Fengsong] Nantong Haimen Peoples Hosp, Nantong 226100, Peoples R China; [Hu, Jun] Shanghai Univ Tradit Chinese Med, Shanghai 201900, Peoples R China		Zhang, WH; Tang, RW (corresponding author), Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Baoshan Branch, Breast Surg Dept, 181 Youyi Rd, Shanghai 201900, Peoples R China.	zwh_08219@163.com; springtrw@sina.cn			Shanghai Municipal Health Commission Traditional Chinese Medicine Heritage and Technology Innovation Project [ZYCC2019020]; National Nature Science Nurturing Project of Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine [GZRPYJJ-201702]; Weihong famous TCM inheritance studio [BSMZYGZS-201909]; Shanghai Key Specialty Training Project of Traditional Chinese Medicine	1. Shanghai Municipal Health Commission Traditional Chinese Medicine Heritage and Technology Innovation Project (ZYCC2019020). 2. National Nature Science Nurturing Project of Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (GZRPYJJ-201702). 3. Zhang Weihong famous TCM inheritance studio (BSMZYGZS-201909). 4. Shanghai Key Specialty Training Project of Traditional Chinese Medicine.	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J. Transl. Res.		2021	13	2					497	514					18	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	QG3IJ	WOS:000617482700005	33594306				2022-04-25	
J	Chi, KH; Ko, HL; Yang, KL; Lee, CY; Chi, MS; Kao, SJ				Chi, Kwan-Hwa; Ko, Hui-Ling; Yang, Kai-Lin; Lee, Cheng-Yen; Chi, Mau-Shin; Kao, Shang-Jyh			Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a second line treatment results in high salvage rates for refractory metastatic solid tumors: a pilot safety and effectiveness analysis in a small patient cohort	ONCOTARGET			English	Article						rapamycin; hydroxychloroquine; metronomic chemotherapy; autophagy	ADVANCED BREAST-CANCER; CELL LUNG-CANCER; PHASE-I TRIAL; GLIOBLASTOMA-MULTIFORME; HEPATOCELLULAR-CARCINOMA; COMBINED AUTOPHAGY; DOUBLE-BLIND; EVEROLIMUS; CYCLOPHOSPHAMIDE; BEVACIZUMAB	Autophagy is an important oncotarget that can be modulated during anti-cancer therapy. Enhancing autophagy using chemotherapy and rapamycin (Rapa) treatment and then inhibiting it using hydroxychloroquine (HCQ) could synergistically improve therapy outcome in cancer patients. It is still unclear whether addition of Rapa and HCQ to chemotherapy could be used for reversing drug resistance. PATIENTS AND METHODS: Twenty-five stage IV cancer patients were identified. They had no clinical response to first-line metronomic chemotherapy; the patients were salvaged by adding an autophagy inducer (Rapa, 2 mg/day) and an autophagosome inhibitor (HCQ, 400 mg/day) to their current metronomic chemotherapy for at least 3 months. Patients included 4 prostate, 4 bladder, 4 lung, 4 breast, 2 colon, and 3 head and neck cancer patients as well as 4 sarcoma patients. RESULTS: Chemotherapy was administered for a total of 137 months. The median duration of chemotherapy cycles per patient was 4 months (95% confidence interval, 3-7 months). The overall response rate to this treatment was of 40%, with an 84% disease control rate. The most frequent and clinically significant toxicities were myelotoxicities. Grade >= 3 leucopenia occurred in 6 patients (24%), grade >= 3 thrombocytopenia in 8 (32%), and anemia in 3 (12%). None of them developed febrile neutropenia. Non-hematologic toxicities were fatigue (total 32%, with 1 patient developing grade 3 fatigue), diarrhea (total 20%, 1 patient developed grade 3 fatigue), reversible grade 3 cardiotoxicity (1 patient), and grade V liver toxicity from hepatitis B reactivation (1 patient). CONCLUSION: Our results of Rapa, HCQ and chemotherapy triplet combination suggest autophagy is a promising oncotarget and warrants further investigation in phase II studies.	[Chi, Kwan-Hwa; Ko, Hui-Ling; Yang, Kai-Lin; Lee, Cheng-Yen; Chi, Mau-Shin] Shin Kong Wu Ho Su Mem Hosp, Dept Radiat Therapy & Oncol, Taipei, Taiwan; [Chi, Kwan-Hwa] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan; [Chi, Kwan-Hwa] Natl Yang Ming Univ, Inst Biomed Imaging & Radiol Sci, Taipei 112, Taiwan; [Kao, Shang-Jyh] Shin Kong Wu Ho Su Mem Hosp, Div Chest Med, Taipei, Taiwan		Chi, KH (corresponding author), Shin Kong Wu Ho Su Mem Hosp, Dept Radiat Therapy & Oncol, Taipei, Taiwan.	M006565@ms.skh.org.tw; M001002@ms.skh.org.tw	Yang, Kai-Lin/AAG-2047-2020				Andre F, 2014, LANCET ONCOL, V15, P580, DOI 10.1016/S1470-2045(14)70138-X; Barber EL, 2013, J GYNECOL ONCOL, V24, P258, DOI 10.3802/jgo.2013.24.3.258; Bello L, 2001, CANCER RES, V61, P7501; Bertolini F, 2003, CANCER RES, V63, P4342; Bocci G, 2002, CANCER RES, V62, P6938; Bray K, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0041831; Cancer Therapy Evaluation Program, COMM TERM CRIT ADV E; Choi H, 2007, J CLIN ONCOL, V25, P1753, DOI 10.1200/JCO.2006.07.3049; Dellapasqua S, 2008, J CLIN ONCOL, V26, P4899, DOI 10.1200/JCO.2008.17.4789; Eisenhauer EA, 2009, EUR J CANCER, V45, P228, DOI 10.1016/j.ejca.2008.10.026; Fan QW, 2010, SCI SIGNAL, V3, DOI 10.1126/scisignal.2001017; Fury MG, 2013, CANCER-AM CANCER SOC, V119, P1823, DOI 10.1002/cncr.27986; Garcia-Saenz JA, 2008, J CHEMOTHERAPY, V20, P632, DOI 10.1179/joc.2008.20.5.632; Goldberg SB, 2012, J THORAC ONCOL, V7, P1602, DOI 10.1097/JTO.0b013e318262de4a; Grimaldi A, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0079658; Guba M, 2002, NAT MED, V8, P128, DOI 10.1038/nm0202-128; Hermans IF, 2003, CANCER RES, V63, P8408; Hsu CH, 2010, J HEPATOL, V53, P126, DOI 10.1016/j.jhep.2010.01.035; Kelley RK, 2013, BRIT J CANCER, V109, P1725, DOI 10.1038/bjc.2013.553; Kim SJ, 2013, INVEST NEW DRUG, V31, P1514, DOI 10.1007/s10637-013-0015-z; Klement G, 2002, CLIN CANCER RES, V8, P221; Kumar P, 2013, CLIN MED INSIGHTS-AR, V6, P35, DOI 10.4137/CMAMD.S5558; Lencioni R, 2010, SEMIN LIVER DIS, V30, P52, DOI 10.1055/s-0030-1247132; MacDonald AS, 2001, TRANSPLANTATION, V71, P271, DOI 10.1097/00007890-200101270-00019; Maes H, 2014, CANCER CELL, V26, P190, DOI 10.1016/j.ccr.2014.06.025; Mahalingam D, 2014, AUTOPHAGY, V10, P1403, DOI 10.4161/auto.29231; Marquette CL, 2013, J CLIN ONCOLOGY OFFI, V31; Martinez-Outschoorn UE, 2010, CELL CYCLE, V9, P4297, DOI 10.4161/cc.9.21.13817; Mason WP, 2012, INVEST NEW DRUG, V30, P2344, DOI 10.1007/s10637-011-9775-5; McCormack FX, 2011, NEW ENGL J MED, V364, P1595, DOI 10.1056/NEJMoa1100391; Mizushima N, 2008, NATURE, V451, P1069, DOI 10.1038/nature06639; Poklepovic A, 2014, AUTOPHAGY, V10, P1478, DOI 10.4161/auto.29428; Rangwala R, 2014, AUTOPHAGY, V10, P1391, DOI 10.4161/auto.29119; Rangwala R, 2014, AUTOPHAGY, V10, P1369, DOI 10.4161/auto.29118; Romiti A, 2013, CANCER CHEMOTH PHARM, V72, P13, DOI 10.1007/s00280-013-2125-x; Rosenfeld MR, 2014, AUTOPHAGY, V10, P1359, DOI 10.4161/auto.28984; Schuetze SM, 2012, EUR J CANCER, V48, P1347, DOI 10.1016/j.ejca.2012.03.022; Seront E, 2013, BRIT J CANCER, V109, P2597, DOI 10.1038/bjc.2013.644; Sotelo J, 2006, ANN INTERN MED, V144, P337, DOI 10.7326/0003-4819-144-5-200603070-00008; Sun JM, 2013, BRIT J CANCER, V109, P1482, DOI 10.1038/bjc.2013.467; Vacca A, 1999, BLOOD, V94, P4143, DOI 10.1182/blood.V94.12.4143.424k26_4143_4155; Vignot S, 2005, ANN ONCOL, V16, P525, DOI 10.1093/annonc/mdi113; Vogl DT, 2014, AUTOPHAGY, V10, P1380, DOI 10.4161/auto.29264; Vredenburgh JJ, 2007, J CLIN ONCOL, V25, P4722, DOI 10.1200/JCO.2007.12.2440; Wang YS HY, 2012, CANC RES, V72, P5611; Werner D, 2013, CANCER MED-US, V2, P325, DOI 10.1002/cam4.77; Xie XQ, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0055096; Yang ZNJ, 2011, MOL CANCER THER, V10, P1533, DOI 10.1158/1535-7163.MCT-11-0047	48	24	28	0	4	IMPACT JOURNALS LLC	ORCHARD PARK	6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA		1949-2553		ONCOTARGET	Oncotarget	JUN 30	2015	6	18					16735	16745		10.18632/oncotarget.3793			11	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	CO2UL	WOS:000359012000094	25944689	Green Published, gold, Green Submitted			2022-04-25	
J	Ni, CL; Li, BL; Ding, YY; Wu, Y; Wang, QY; Wang, JR; Cheng, JJ				Ni, Chunlei; Li, Bailiang; Ding, Yangyue; Wu, Yue; Wang, Qiuye; Wang, Jiarong; Cheng, Jianjun			Anti-Cancer Properties of Coix Seed Oil against HT-29 Colon Cells through Regulation of the PI3K/AKT Signaling Pathway	FOODS			English	Article						coix seed oil; anti-colon cancer; cell cycle; apoptosis; PI3K/AKT	HEPATOCELLULAR-CARCINOMA; APOPTOSIS INDUCTION; CYCLE ARREST; FATTY-ACID; INHIBITION; DOXORUBICIN; AUTOPHAGY; CHICKENS; EXTRACT; GROWTH	This study aims to observe the effects of coix seed oil (CSO) on HT-29 cells and investigate its possible regulation mechanism of the PI3K/Akt signaling pathway. Fatty acid analysis showed that coix seed oil mainly contains oleic acid (50.54%), linoleic acid (33.76%), palmitic acid (11.74%), and stearic acid (2.45%). Fourier transform infrared results found that the fatty acid functional groups present in the oil matched well with the vegetable oil band. The results from CCK-8 assays showed that CSO dose-dependently and time-dependently inhibited the viability of HT-29 cells in vitro. CSO inhibited cell viability, with IC50 values of 5.30 mg/mL for HT-29 obtained after 24 h treatment. Morphological changes were observed by apoptotic body/cell nucleus DNA (Hoechst 33258) staining using inverted and fluorescence microscopy. Moreover, flow cytometry analysis was used to evaluate the cell cycle and cell apoptosis. It showed that CSO induced cell apoptosis and cycle arrest in the G(2) phase. Quantitative real-time PCR and Western blotting revealed that CSO induced cell apoptosis by downregulating the PI3K/AKT signaling pathway. Additionally, CSO can cause apoptosis in cancer cells by activating caspase-3, up-regulating Bax, and down-regulating Bcl-2. In conclusion, the results revealed that CSO induced G(2) arrest and apoptosis of HT-29 cells by regulating the PI3K/AKT signaling pathway.	[Ni, Chunlei; Li, Bailiang; Ding, Yangyue; Wu, Yue; Wang, Qiuye; Wang, Jiarong; Cheng, Jianjun] Northeast Agr Univ, Coll Food Sci, Harbin 150030, Peoples R China		Cheng, JJ (corresponding author), Northeast Agr Univ, Coll Food Sci, Harbin 150030, Peoples R China.	jjcheng@neau.edu.cn			National Key Research and Development Program of China [2017YFD0401204-5]	FundingThis research was funded by the National Key Research and Development Program of China, grant number 2017YFD0401204-5.	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J	Brun, S; Pascussi, JM; Gifu, EP; Bestion, E; Macek-Jilkova, Z; Wang, GX; Bassissi, F; Mezouar, S; Courcambeck, J; Merle, P; Decaens, T; Pannequin, J; Halfon, P; de Fromentel, CC				Brun, Sonia; Pascussi, Jean-Marc; Gifu, Elena Patricia; Bestion, Eloine; Macek-Jilkova, Zuzana; Wang, Guanxiong; Bassissi, Firas; Mezouar, Soraya; Courcambeck, Jerome; Merle, Philippe; Decaens, Thomas; Pannequin, Julie; Halfon, Philippe; de Fromentel, Claude Caron			GNS561, a New Autophagy Inhibitor Active against Cancer Stem Cells in Hepatocellular Carcinoma and Hepatic Metastasis from Colorectal Cancer	JOURNAL OF CANCER			English	Article						GNS561; cancer stem cell; liver cancer; colorectal cancer; lysosome; therapy	CHEMORESISTANCE; SALINOMYCIN; RESISTANCE	Patients with advanced hepatocellular carcinoma (HCC) or metastatic colorectal cancer (mCRC) have a very poor prognosis due to the lack of efficient treatments. As observed in several other tumors, the effectiveness of treatments is mainly hampered by the presence of a highly tumorigenic sub-population of cancer cells called cancer stem cells (CSCs). Indeed, CSCs are resistant to chemotherapy and radiotherapy and can regenerate the tumor bulk. Hence, innovative drugs that are efficient against both bulk tumor cells and CSCs would likely improve cancer treatment. In this study, we demonstrated that GNS561, a new autophagy inhibitor that induces lysosomal cell death, showed significant activity against not only the whole tumor population but also a sub-population displaying CSC features (high ALDH activity and tumorsphere formation ability) in HCC and in liver mCRC cell lines. These results were confirmed in vivo in HCC from a DEN-induced cirrhotic rat model in which GNS561 decreased tumor growth and reduced the frequency of CSCs (CD90(+)CD45(-)). Thus, GNS561 offers great promise for cancer therapy by exterminating both the tumor bulk and the CSC sub-population. Accordingly, a global phase 1b clinical trial in liver cancers was recently completed.	[Brun, Sonia; Bestion, Eloine; Bassissi, Firas; Mezouar, Soraya; Courcambeck, Jerome; Halfon, Philippe] Genosci Pharma, 10 Rue Iena, F-13006 Marseille, France; [Pascussi, Jean-Marc; Pannequin, Julie] Univ Montpellier, IGF, CNRS, INSERM, Montpellier, France; [Gifu, Elena Patricia; Wang, Guanxiong; Merle, Philippe; de Fromentel, Claude Caron] Univ Lyon 1 Ctr Leon Berard, CRCL, INSERM, CNRS 5286,U1052, Lyon, France; [Bestion, Eloine] Aix Marseille Univ, IHU Mediterranee Infect, AP HM, MEPHI,IRD, Marseille, France; [Macek-Jilkova, Zuzana; Decaens, Thomas] Inst Adv Biosci, Res Ctr UGA, INSERM, U1209,CNRS 5309, La Tronche, France; [Macek-Jilkova, Zuzana; Decaens, Thomas] Univ Grenoble Alpes, Fac Med, Grenoble, France; [Macek-Jilkova, Zuzana; Decaens, Thomas] CHU Grenoble, Clin Univ Hepatogastroenterol, Pole Digidune, Grenoble, France; [Merle, Philippe] Hosp Civils Lyon, Hepatol & Gastroenterol Unit, Croix Rousse Hosp, Lyon, France		Brun, S; Halfon, P (corresponding author), Genosci Pharma, 10 Rue Iena, F-13006 Marseille, France.; de Fromentel, CC (corresponding author), CRCL, INSERM, U1052, 151 Cours A Thomas, F-69003 Lyon, France.	brun.sonia@hotmail.fr; phalfon@genosciencepharma.com; claude.de-fromentel@inserm.fr	Macek Jílková, Zuzana/N-4051-2014	Macek Jílková, Zuzana/0000-0002-2553-5971			Bonnet D, 2005, CELL PROLIFERAT, V38, P357, DOI 10.1111/j.1365-2184.2005.00353.x; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Brun S, 2020, GNS561 CLIN STAG PPT GNS561 CLIN STAG PPT; Brun S, 2019, INVEST NEW DRUG, V37, P1135, DOI 10.1007/s10637-019-00741-3; Cao JX, 2019, THERANOSTICS, V9, P811, DOI 10.7150/thno.29271; Cao L, 2011, BMC GASTROENTEROL, V11, DOI 10.1186/1471-230X-11-71; Cash TP, 2020, CANCERS BASEL, P12; Chen J, 2015, CANCER LETT, V367, P1, DOI 10.1016/j.canlet.2015.06.019; Cheng CC, 2019, ONCOTARGETS THER, V12, P8217, DOI 10.2147/OTT.S217468; Chiba T, 2006, HEPATOLOGY, V44, P240, DOI 10.1002/hep.21227; Clarke Michael F, 2006, Cancer Res, V66, P9339, DOI 10.1158/0008-5472.CAN-06-3126; ClinicalTrials. gov, STUDY GNS561 PAT STUDY GNS561 PAT; Das PK, 2020, CELLS-BASEL, V9, DOI 10.3390/cells9061392; El Hout M, 2020, MOL CANCER, V19, DOI 10.1186/s12943-019-1126-8; Feng Y, 2020, EXP CELL RES, V394, DOI 10.1016/j.yexcr.2020.112162; Flores-Tellez TNJ, 2017, WORLD J GASTROENTERO, V23, P6750, DOI 10.3748/wjg.v23.i37.6750; Grillet F, 2017, GUT, V66, P1802, DOI 10.1136/gutjnl-2016-311447; Harding J.J., 2021, JCO, V39; Huang EH, 2009, CANCER RES, V69, P3382, DOI 10.1158/0008-5472.CAN-08-4418; Johnson S, 2013, BIOPROTOC, P3; Lee CH, 2016, ONCOTARGET, V7, P1215, DOI 10.18632/oncotarget.6261; Li N, 2019, THER ADV GASTROENTER, V12, DOI 10.1177/1756284818821560; Lim J, 2020, FRONT PHARMACOL, V11, DOI 10.3389/fphar.2020.590344; Ma XL, 2019, BMC CANCER, V19, DOI 10.1186/s12885-019-5963-z; Mandhair HK, 2020, WORLD J STEM CELLS, V12, P303, DOI 10.4252/wjsc.v12.i5.303; Morgan MJ, 2018, P NATL ACAD SCI USA, V115, pE8479, DOI 10.1073/pnas.1706526115; Motawi TK, 2016, TUMOR BIOL, V37, P1617, DOI 10.1007/s13277-015-3920-2; Muller S, 2020, NAT CHEM, V12, P929, DOI 10.1038/s41557-020-0513-5; Nazio F, 2019, CELL DEATH DIFFER, V26, P690, DOI 10.1038/s41418-019-0292-y; Ojha R, 2015, BIORESEARCH OPEN ACC, V4, P97, DOI 10.1089/biores.2014.0035; Pattabiraman DR, 2014, NAT REV DRUG DISCOV, V13, P497, DOI 10.1038/nrd4253; Quintana E, 2008, NATURE, V456, P593, DOI 10.1038/nature07567; Rebecca VW, 2019, CANCER DISCOV, V9, P220, DOI 10.1158/2159-8290.CD-18-0706; Salerno M, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0110340; Schulte LA, 2020, CANCERS, V12, DOI 10.3390/cancers12030684; Sharif T, 2017, AUTOPHAGY, V13, P264, DOI 10.1080/15548627.2016.1260808; Smith AG, 2019, J PATHOL, V247, P708, DOI 10.1002/path.5222; Sukhai MA, 2013, J CLIN INVEST, V123, P315, DOI 10.1172/JCI64180; Sun JH, 2016, WORLD J GASTROENTERO, V22, P3547, DOI 10.3748/wjg.v22.i13.3547; Tanaka K, 2015, ONCOTARGET, V6, P24722, DOI 10.18632/oncotarget.4406; Mai TT, 2017, NAT CHEM, V9, P1025, DOI [10.1038/NCHEM.2778, 10.1038/nchem.2778]; Uchida Y, 2010, ONCOL REP, V24, P1147, DOI 10.3892/or_00000966; Vassalli G, 2019, STEM CELLS INT, V2019, DOI 10.1155/2019/3904645; Versini A, 2020, CHEM-EUR J, V26, P7416, DOI 10.1002/chem.202000335; Vitale I, 2015, INT J DEV BIOL, V59, P95, DOI 10.1387/ijdb.150082iv; Wu YF, 2020, FRONT PHARMACOL, V11, DOI 10.3389/fphar.2020.00198; Xia P, 2015, AM J CANCER RES, V5, P1602; Yang ZF, 2008, HEPATOLOGY, V47, P919, DOI 10.1002/hep.22082; Yang ZF, 2008, CANCER CELL, V13, P153, DOI 10.1016/j.ccr.2008.01.013; Yue W, 2013, AUTOPHAGY, V9, P714, DOI 10.4161/auto.23997; Zhou Yujuan, 2018, Oncotarget, V9, P33403, DOI 10.18632/oncotarget.23607	51	2	2	0	2	IVYSPRING INT PUBL	LAKE HAVEN	PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA	1837-9664			J CANCER	J. Cancer		2021	12	18					5432	5438		10.7150/jca.58533			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	TI4XG	WOS:000672805200007	34405006	Green Submitted, Green Published, gold			2022-04-25	
J	Su, CC				Su, Chin-Cheng			Sann-Joong-Kuey-Jian-Tang decreases the protein expression of mammalian target of rapamycin but increases microtubule associated protein II light chain 3 expression to inhibit human BxPC-3 pancreatic carcinoma cells	MOLECULAR MEDICINE REPORTS			English	Article						Sann-Joong-Kuey-Jian-Tang; mammalian target of rapamycin; microtubule associated protein II light chain 3; autophagy; human pancreatic carcinoma BxPC-3 cells	TNF-ALPHA; CANCER CELLS; AUTOPHAGY; DEATH; MCL-1; TCTP; BAX	Sann-Joong-Kuey-Jian-Tang (SJKJT), a Traditional Chinese Medicinal prescription, has been used for the treatment of lymphadenopathy and solid tumors, and has shown therapeutic potential in a number of human malignant tumor cell lines, such as Hep-G2 hepatocellular carcinoma cells. Previous mechanistic studies demonstrated that SJKJT inhibited the proliferation of BxPC-3 pancreatic carcinoma cells through the extrinsic and intrinsic apoptotic pathways in vitro. SJKJT was also shown to be cytotoxic to colo 205 colon cancer cells by inducing autophagy in vitro. The present study therefore investigated molecular mechanisms of autophagy in human BxPC-3 pancreatic cancer cells treated with SJKJT. The cytotoxic effects of SJKJT on BxPC-3 human pancreatic carcinoma cells were evaluated using an MTT assay. Furthermore, the expression of autophagy-associated proteins, including mammalian target of rapamycin (mTOR), beclin-1, autophagocytosis-associated protein (Atg)3, Atg7, Atg5-Atg12 and microtubule-associated protein II light chain 3 (LC3-II), was assessed using western blot analysis. The results demonstrated that BxPC-3 cells treated with SJKJT exhibited decreased expression levels of mTOR and increased expression of LC3-II protein. In addition, the expression of the beclin-1, Atg3, Atg7 and Atg5-Atg12 proteins was increased during the first 24 h, but decreased from 48 to 72 h. The results showed that SJKJT inhibited the proliferation of human BxPC-3 pancreatic cancer cells in vitro. A possible underlying molecular mechanism may be the induction of autophagy. Further investigation into the therapeutic potential of SJKJT in human pancreatic cancer is required.	[Su, Chin-Cheng] Changhua Christian Hosp, Tumor Res Ctr Integrat Med, Changhua 50006, Taiwan; [Su, Chin-Cheng] Changhua Christian Hosp, Comprehens Breast Canc Ctr, Changhua 50006, Taiwan; [Su, Chin-Cheng] Changhua Christian Hosp, Dept Surg, Changhua 50006, Taiwan; [Su, Chin-Cheng] China Med Univ, Sch Chinese Med, Coll Chinese Med, Taichung 40651, Taiwan		Su, CC (corresponding author), Changhua Christian Hosp, Tumor Res Ctr Integrat Med, 135 Nan Hsiao St, Changhua 50006, Taiwan.	succ.maeva@msa.hinet.net			Changhua Christian Hospital [100-CCH-ICO-06-1]	This study was supported by the Changhua Christian Hospital (grant no. 100-CCH-ICO-06-1).	Chen YL, 2013, MOL MED REP, V7, P1487, DOI 10.3892/mmr.2013.1381; Cheng CY, 2010, MOL MED REP, V3, P63, DOI 10.3892/mmr_00000219; Cheng CY, 2009, MOL MED REP, V2, P707, DOI 10.3892/mmr_00000160; Chien SY, 2013, INT J MOL MED, V32, P85, DOI 10.3892/ijmm.2013.1369; CLARKE PGH, 1990, ANAT EMBRYOL, V181, P195, DOI 10.1007/bf00174615; Dalby KN, 2010, AUTOPHAGY, V6, P322, DOI 10.4161/auto.6.3.11625; Fujii S, 2008, CANCER SCI, V99, P1813, DOI 10.1111/j.1349-7006.2008.00893.x; Kondo Y, 2006, AUTOPHAGY, V2, P85, DOI 10.4161/auto.2.2.2463; Moretti L, 2007, DRUG RESIST UPDATE, V10, P135, DOI 10.1016/j.drup.2007.05.001; Mujumdar N, 2010, GASTROENTEROLOGY, V139, P598, DOI 10.1053/j.gastro.2010.04.046; Siegel R, 2012, CA-CANCER J CLIN, V62, P10, DOI 10.3322/caac.20138; Siegel R, 2011, CA-CANCER J CLIN, V61, P212, DOI 10.3322/caac.20121; Verhoef Marja J, 2005, Integr Cancer Ther, V4, P274, DOI 10.1177/1534735405282361; YANG CH, 1994, ADV SPACE RES-SERIES, V14, P115, DOI 10.1016/0273-1177(94)90459-6; Yang SH, 2011, GENE DEV, V25, P717, DOI 10.1101/gad.2016111; Yang YP, 2005, ACTA PHARMACOL SIN, V26, P1421, DOI 10.1111/j.1745-7254.2005.00235.x	16	2	2	0	6	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1791-2997	1791-3004		MOL MED REP	Mol. Med. Rep.	APR	2015	11	4					3160	3166		10.3892/mmr.2014.3090			7	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	CE3FG	WOS:000351711100112	25516264	Bronze			2022-04-25	
J	Pattingre, S; De Vries, L; Bauvy, C; Chantret, I; Cluzeaud, F; Ogier-Denis, E; Vandewalle, A; Codogno, P				Pattingre, S; De Vries, L; Bauvy, C; Chantret, I; Cluzeaud, F; Ogier-Denis, E; Vandewalle, A; Codogno, P			The g-protein regulator AGS3 controls an early event during macroautophagy in human intestinal HT-29 cells	JOURNAL OF BIOLOGICAL CHEMISTRY			English	Article							CONTROLS AUTOPHAGIC SEQUESTRATION; ALPHA-INTERACTING PROTEIN; HETEROTRIMERIC G-PROTEIN; TETRATRICOPEPTIDE REPEAT; SUBCELLULAR-DISTRIBUTION; DISSOCIATION INHIBITOR; RAT HEPATOCYTES; GOLGI MEMBRANES; LINE HT-29; VACUOLES	AGS3 contains GoLoco or G-protein regulatory motifs in its COOH-terminal half that stabilize the GDP-bound conformation of the alpha-subunit of the trimeric G(i3) protein. The latter is part of a signaling pathway that controls the lysosomal-autophagic catabolism in human colon cancer HT-29 cells. In the present work we show that the mRNA encoding for AGS3 is expressed in human intestinal cell lines (Caco-2 and HT-29) whatever their state of differentiation. Together with the full-length form, minute amounts of the mRNA encoding a NH2-terminal truncated form of AGS3, previously characterized in cardiac tissues, were also detected. Both the endogenous form of AGS3 and a tagged expressed form have a localization compatible with a role in the Galpha(i3)-dependent control of autophagy. Accordingly, expressing its non-Galpha(i3)-interacting NH2-terminal domain or its Galpha(i3)-interacting COOH-terminal domain reversed the stimulatory role of AGS3 on autophagy. On the basis of biochemical and morphometric analysis, we conclude that AGS3 is involved in an early event during the autophagic pathway probably prior to the formation of the autophagosome. These data demonstrate that AGS3 is a novel partner of the Galpha(i3) protein in the control of a major catabolic pathway.	INSERM, U504, F-94807 Villejuif, France; Univ Calif San Diego, Dept Mol & Cellular Biol, La Jolla, CA 92093 USA; Univ Paris 07, INSERM, U478, F-75018 Paris, France		Codogno, P (corresponding author), INSERM, U504, 16 Ave Paul Vaillant Couturier, F-94807 Villejuif, France.		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Biol. Chem.	JUN 6	2003	278	23					20995	21002		10.1074/jbc.M300917200			8	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	684WY	WOS:000183230500072	12642577	hybrid			2022-04-25	
J	Li, L; Jing, LL; Wang, JJ; Xu, WJ; Gong, XL; Zhao, YY; Ma, Y; Yao, XQ; Sun, XG				Li, Lu; Jing, Linlin; Wang, Junjiang; Xu, Wenjuan; Gong, Xianling; Zhao, Yiye; Ma, Ye; Yao, Xueqing; Sun, Xuegang			Autophagic flux is essential for the downregulation of D-dopachrome tautomerase by atractylenolide I to ameliorate intestinal adenoma formation	JOURNAL OF CELL COMMUNICATION AND SIGNALING			English	Article						Atractylenolide I; Autophagy; Adenoma; D-dopachrome tautomerase; p53; Acetylation; Sirt 1	MIGRATION-INHIBITORY FACTOR; COLORECTAL-CANCER; SIRT1; ACTIVATION; PHOSPHORYLATION; DEACETYLATION; PATHOGENESIS; HOMOLOG; COMPLEX	Colorectal cancer is generally believed to progress through an adenoma - carcinoma sequence. Adenomatous polyposis coli (APC) mutations serve as the initiating event in adenoma formation. The Apc(Min/+) mouse harbors a mutation in the APC gene, which is similar or identical to the mutation found in individuals with familial adenomatous polyposis and 70% of all sporadic CRC cases. Autophagy is a constitutive process required for proper cellular homeostasis. However, its role in intestinal adenoma formation is still controversial. Atractylenolide I (AT1) is a sesquiterpenoid that possesses various clinically relevant properties such as anti-tumor and anti-inflammatory activities. The role of AT1 on adenoma formation was tested in Apc(Min/+) mice and its underlying mechanism in regulating autophagy was documented. D-dopachrome tautomerase (D-DT) was identified as a potential target of AT1 by an proteomics-based approach. The effects of p53 modification on autophgic flux was monitored in p53(-/-) and p53(+/+) HCT116 cells. Small interfering RNA was used to investigate the function of Atg7 and D-DT on autophagy programme induce by AT1. AT1 effectively reduced the formation of adenoma and downregulated the tumorigenic proteins in Apc(Min/+) mice. Importantly, AT1 stimulated autophagic flux through downregulating acetylation of p53. Activation of Sirt1 by AT1 was essential for the deacetylation of p53 and downregulation of D-DT. The lowered expression of COX-2 and -catenin by AT1 were partly recovered by Atg7 knockdown. AT1 activates autophagy machinery to downregulate D-DT and reduce intestinal adenoma formation. This discovery provides evidence in vivo and in vitro that inducing autophagy by natural products maybe a potential therapy to ameliorate colorectal adenoma formation.	[Li, Lu; Gong, Xianling; Ma, Ye; Sun, Xuegang] Southern Med Univ, Sch Tradit Chinese Med, Guangzhou 510515, Guangdong, Peoples R China; [Jing, Linlin; Zhao, Yiye; Sun, Xuegang] Southern Med Univ, TCM Integrated Hosp, Guangzhou 510315, Guangdong, Peoples R China; [Wang, Junjiang; Yao, Xueqing] Guangdong Gen Hosp, Dept Gastrointestinal Surg, Guangzhou 510120, Guangdong, Peoples R China; [Xu, Wenjuan] Binzhou Med Univ, Sch Tradit Chinese Med, Yantai 256600, Shandong, Peoples R China; [Gong, Xianling] Guangdong Med Univ, Sch Pharm, Dongguan 523808, Guangdong, Peoples R China		Sun, XG (corresponding author), Southern Med Univ, Sch Tradit Chinese Med, Guangzhou 510515, Guangdong, Peoples R China.; Sun, XG (corresponding author), Southern Med Univ, TCM Integrated Hosp, Guangzhou 510315, Guangdong, Peoples R China.	549812447@qq.com; jll47379@163.com; langyisheng6726582@qq.com; xwjycd@163.com; 1290064145@qq.com; 1056882895@qq.com; 915242251@qq.com; yjb9211@21cn.com; sxg_smu@126.com		SUN, Xuegang/0000-0001-6581-0520	National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81573848, 81774172, 81472315]; Guangdong Natural Science FoundationNational Natural Science Foundation of Guangdong Province [2014A030313323]; Planned Science Technology Project of Guangzhou [201607010146]; Guangdong Province Bureau of Traditional Chinese Medicine Scientific Research Project [20151024, 20161161]	Founed by the National Science Foundation of China (81573848, 81774172, 81472315), Guangdong Natural Science Foundation (2014A030313323), Planned Science Technology Project of Guangzhou (201607010146), Guangdong Province Bureau of Traditional Chinese Medicine Scientific Research Project (No: 20151024, 20161161).	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Cell Commun. Signal	DEC	2018	12	4					689	698		10.1007/s12079-018-0454-6			10	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	HC7DP	WOS:000451961100006	29368299	Green Published			2022-04-25	
J	Wu, QH; Wang, X; Nepovimova, E; Miron, A; Liu, QY; Wang, Y; Su, DX; Yang, HL; Li, L; Kuca, K				Wu, Qinghua; Wang, Xu; Nepovimova, Eugenie; Miron, Anca; Liu, Qianying; Wang, Yun; Su, Dongxiao; Yang, Hualin; Li, Li; Kuca, Kamil			Trichothecenes: immunomodulatory effects, mechanisms, and anti-cancer potential	ARCHIVES OF TOXICOLOGY			English	Review						T-2 toxin; Deoxynivalenol; Immunomodulation; Anti-cancer; Signaling pathway; Autophagy; Immune evasion	RESPIRATORY SYNDROME VIRUS; RIBOTOXIC STRESS-RESPONSE; ACTIVATED PROTEIN-KINASE; TRAIL-INDUCED APOPTOSIS; STEROID-RECEPTOR COACTIVATOR-3; DEOXYNIVALENOL DON MYCOTOXIN; SYSTEMIC-LUPUS-ERYTHEMATOSUS; NATURALLY CONTAMINATED FEED; HYPOXIA-INDUCIBLE FACTOR-1; MESSENGER-RNA EXPRESSION	Paradoxically, trichothecenes have both immunosuppressive and immunostimulatory effects. The underlying mechanisms have not been fully explored. Early studies show that dose, exposure timing, and the time at which immune function is assessed influence whether trichothecenes act in an immunosuppressive or immunostimulatory fashion. Recent studies suggest that the immunomodulatory function of trichothecenes is also actively shaped by competing cell-survival and death-signaling pathways. Autophagy may also promote trichothecene immunosuppression, although the mechanism may be complicated. Moreover, trichothecenes may generate an "immune evasion" milieu that allows pathogens to escape host and vaccine immune defenses. Some trichothecenes, especially macrocyclic trichothecenes, also potently kill cancer cells. T-2 toxin conjugated with anti-cancer monoclonal antibodies significantly suppresses the growth of thymoma EL-4 cells and colon cancer cells. The type B trichothecene diacetoxyscirpenol specifically inhibits the tumor-promoting factor HIF-1 in cancer cells under hypoxic conditions. Trichothecin markedly inhibits the growth of multiple cancer cells with constitutively activated NF-kappa B. The type D macrocyclic toxin Verrucarin A is also a promising therapeutic candidate for leukemia, breast cancer, prostate cancer, and pancreatic cancer. The anti-cancer activities of trichothecenes have not been comprehensively summarized. Here, we first summarize the data on the immunomodulatory effects of trichothecenes and discuss recent studies that shed light on the underlying cellular and molecular mechanisms. These mechanisms include autophagy and major signaling pathways and their crosstalk. Second, the anti-cancer potential of trichothecenes and the underlying mechanisms will be discussed. We hope that this review will show how trichothecene bioactivities can be exploited to generate therapies against pathogens and cancer.	[Wu, Qinghua; Wang, Yun; Su, Dongxiao; Yang, Hualin; Li, Li] Yangtze Univ, Inst Biomed, Coll Life Sci, Jingzhou 434025, Peoples R China; [Wu, Qinghua; Nepovimova, Eugenie; Kuca, Kamil] Univ Hradec Kralove, Dept Chem, Fac Sci, Hradec Kralove, Czech Republic; [Wang, Xu; Liu, Qianying] Huazhong Agr Univ, Natl Reference Lab Vet Drug Residues HZAU, Wuhan 430070, Hubei, Peoples R China; [Wang, Xu; Liu, Qianying] Huazhong Agr Univ, MAO Key Lab Detect Vet Drug Residues, Wuhan 430070, Hubei, Peoples R China; [Miron, Anca] Univ Med & Pharm Grigore T Popa, Dept Pharmacognosy, Fac Pharm, Iasi, Romania		Wu, QH (corresponding author), Yangtze Univ, Inst Biomed, Coll Life Sci, Jingzhou 434025, Peoples R China.; Wu, QH; Kuca, K (corresponding author), Univ Hradec Kralove, Dept Chem, Fac Sci, Hradec Kralove, Czech Republic.	wqh212@hotmail.com; kamil.kuca@uhk.cz	Nepovimova, Eugenie/AAU-7268-2020; Kuca, Kamil/D-1396-2011	Nepovimova, Eugenie/0000-0003-0281-246X; Kuca, Kamil/0000-0001-9664-1109	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31602114, 31572575]; Yangtze Fund for Youth Teams of Science and Technology Innovation [2016cqt02]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [2662016PY115]; project of long-term development plan UHK	This work was supported by the National Natural Science Foundation of China (Grant No. 31602114 and 31572575), the Yangtze Fund for Youth Teams of Science and Technology Innovation (2016cqt02), the Fundamental Research Funds for the Central Universities (2662016PY115), and the project of long-term development plan UHK.	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Toxicol.	DEC	2017	91	12					3737	3785		10.1007/s00204-017-2118-3			49	Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Toxicology	FP0CJ	WOS:000417266400002	29152681				2022-04-25	
J	Sivridis, E; Koukourakis, MI; Mendrinos, SE; Karpouzis, A; Fiska, A; Kouskoukis, C; Giatromanolaki, A				Sivridis, Efthimios; Koukourakis, Michael I.; Mendrinos, Savvas E.; Karpouzis, Antonios; Fiska, Aliki; Kouskoukis, Constantinos; Giatromanolaki, Alexandra			Beclin-1 and LC3A expression in cutaneous malignant melanomas: a biphasic survival pattern for beclin-1	MELANOMA RESEARCH			English	Article						autophagy; beclin 1; cutaneous malignant melanoma; hypoxia; light chain 3A	COLORECTAL-CANCER; PROGNOSTIC-SIGNIFICANCE; INDUCED AUTOPHAGY; CELL-DEATH; HYPOXIA; PROTEIN; GENE; METASTASIS; TOLERANCE; MICROENVIRONMENT	Autophagy is an intracellular pathway for the degradation of long-lived proteins and damaged organelles. It is, in essence, a recycling process allowing cells to survive oxygen and nutrient depletion. The expression of two autophagy-related proteins, beclin 1 and light chain 3A (LC3A) was investigated in 79 nodular cutaneous melanomas. The results were correlated with histopathological factors, vascular density, and hypoxia-related proteins [hypoxia-inducible factors (HIF1 alpha and HIF2 alpha) and lactate dehydrogenase 5]. The reactivity of both autophagy-related proteins was uniformly cytoplasmically diffused. High beclin 1 and LC3A reactivity was related to tumor hypoxia, as this was inferred from the intense expression of HIF1a and lactate dehydrogenase 5, whereas low beclin 1 and LC3A expression was linked with an increased vascular density. In addition, beclin 1 was related to disease-specific survival which, however, exposed a biphasic pattern. A strong beclin 1 expression extending over a tumor area of more than 50% (high) was associated with an increased rate of early deaths, whereas a similarly strong, but less-extensive cytoplasmic reactivity (< 10% tumor area; low) defined a sharp fall in the survival 5 years after surgery. Furthermore, the low beclin 1 expression was associated with high Breslow's depth, high Clark's level, and ulceration. Low LC3A expression was also related to ulceration, but not to other histopathological features nor prognosis. In multivariate analysis, beclin 1 was an independent prognostic variable. It is concluded that extensive autophagic activity is generated by tumor hypoxia and anaerobic glycolysis, whereas angiogenesis maintains low autophagic activity. Atg6/beclin 1 was proved to be capable of deciphering the prognosis in cutaneous malignant melanoma, but the matter requires further investigation. Melanoma Res 21:188-195 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.	[Sivridis, Efthimios; Fiska, Aliki; Giatromanolaki, Alexandra] Democritus Univ Thrace, Sch Med, Dept Pathol, Alexandroupolis 68100, Greece; [Koukourakis, Michael I.] Democritus Univ Thrace, Sch Med, Dept Radiotherapy Oncol, Alexandroupolis 68100, Greece; [Karpouzis, Antonios; Kouskoukis, Constantinos] Democritus Univ Thrace, Sch Med, Dept Dermatol, Alexandroupolis 68100, Greece; Univ Gen Hosp Alexandroupolis, Alexandroupolis 68100, Greece; [Mendrinos, Savvas E.] NYU, Sch Med, Langone Med Ctr, Dept Pathol, New York, NY USA		Giatromanolaki, A (corresponding author), Democritus Univ Thrace, Sch Med, Dept Pathol, POB 12, Alexandroupolis 68100, Greece.	agiatrom@med.duth.gr	Fiska, Aliki/ABE-7231-2020	Fiska, Aliki/0000-0003-1787-6116			Ahn CH, 2007, APMIS, V115, P1344, DOI 10.1111/j.1600-0463.2007.00858.x; Aita VM, 1999, GENOMICS, V59, P59, DOI 10.1006/geno.1999.5851; Aoki H, 2008, AUTOPHAGY, V4, P467, DOI 10.4161/auto.5668; Balch CM, 2009, J CLIN ONCOL, V27, P6199, DOI 10.1200/JCO.2009.23.4799; 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JUN	2011	21	3					188	195		10.1097/CMR.0b013e328346612c			8	Oncology; Dermatology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Dermatology; Research & Experimental Medicine	758EO	WOS:000290144400004	21537144				2022-04-25	
J	Zhao, Y; Guo, QL; Zhao, K; Zhou, YX; Li, WJ; Pan, CY; Qiang, L; Li, ZY; Lu, N				Zhao, Yue; Guo, Qinglong; Zhao, Kai; Zhou, Yuxin; Li, Wenjun; Pan, Chuyue; Qiang, Lei; Li, Zhiyu; Lu, Na			Small molecule GL-V9 protects against colitis-associated colorectal cancer by limiting NLRP3 inflammasome through autophagy	ONCOIMMUNOLOGY			English	Article						autophagy; colitis-associated colorectal cancer; colitis; GL-V9; NLRP3 inflammasome	ULCERATIVE-COLITIS; INTESTINAL INFLAMMATION; CROHNS-DISEASE; BOWEL-DISEASE; RISK-FACTOR; INNATE; MECHANISMS; EXPRESSION; PHOSPHORYLATION; CARCINOGENESIS	Emerging evidence suggests that NLRP3 inflammasome provides a link between colitis-associated colorectal cancer and inflammatory bowel diseases. Autophagy is induced in macrophages by AMPK activation and regulates NLRP3 inflammasome to maintain intracellular homeostasis. Here we report that a small-molecule AMPK activator (GL-V9) exerts potent anti-inflammatory effects on macrophages invitro and in vivo, which trigger autophagy to degraded NLRP3 inflammasome. Treatment with GL-V9 protected against colitis and tumorigenesis in colitis-associated colorectal cancer. This suggests that GL-V9 may be an interesting candidate for clinical evaluation in the treatment of colitis-associated colorectal cancer.	[Zhao, Yue; Guo, Qinglong; Zhao, Kai; Zhou, Yuxin; Li, Wenjun; Pan, Chuyue; Lu, Na] China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Jiangsu Key Lab Carcinogenesis & Intervent, State Key Lab Nat Med, 24 Tongjiaxiang, Nanjing, Jiangsu, Peoples R China; [Li, Zhiyu] China Pharmaceut Univ, Sch Pharm, 24 Tongjiaxiang, Nanjing, Jiangsu, Peoples R China; [Qiang, Lei] Univ Chicago, Dept Med, Sect Dermatol, 5841 S Maryland Ave, Chicago, IL 60637 USA		Lu, N (corresponding author), China Pharmaceut Univ, State Key Lab Nat Med, 24 Tongjiaxiang, Nanjing 210009, Jiangsu, Peoples R China.	luna555@163.com	Qiang, Lei/B-2763-2012	Qiang, Lei/0000-0002-7164-3164	National Science & Technology Major Project [2012ZX09304-001, 2013ZX09103-001-007]; Program for Changjiang Scholars and Innovative Research Team in UniversityProgram for Changjiang Scholars & Innovative Research Team in University (PCSIRT) [IRT1193]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [91029744, 81373448, 81373449]; Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [SKLNMZZCX201606]	This work was supported by the National Science & Technology Major Project (No. 2012ZX09304-001, No. 2013ZX09103-001-007), Program for Changjiang Scholars and Innovative Research Team in University (IRT1193), the National Natural Science Foundation of China (No. 91029744, No. 81373448 and No. 81373449), the Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (NO. SKLNMZZCX201606).	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J	Zhao, HD; Chen, DL; Cao, R; Wang, SQ; Yu, DD; Liu, YK; Jiang, Y; Xu, M; Luo, J; Wang, SY				Zhao, Haodong; Chen, Danlei; Cao, Rui; Wang, Shiqing; Yu, Dandan; Liu, Yakun; Jiang, Yu; Xu, Mei; Luo, Jia; Wang, Siying			Alcohol consumption promotes colorectal carcinoma metastasis via a CCL5-induced and AMPK-pathway-mediated activation of autophagy	SCIENTIFIC REPORTS			English	Article							BREAST-CANCER CELLS; PROTEIN-KINASE; CHEMOKINE CCL5; ENERGY SENSOR; INVASION; MIGRATION; INHIBITION; STATISTICS; MICROGLIA; BEVERAGES	There is a definite relationship between alcohol consumption and colorectal cancer (CRC) development. We investigated effect of alcohol consumption on CRC patients' progression and prognosis by utilizing epidemiological data and found patients with alcohol consumption increased risks of tumor-node-metastasis (TNM), organ metastasis and poorer prognosis. Because their tumor tissues displayed increased expression of C-C chemokine ligand 5 (CCL5), we hypothesized CCL5 might participate in cancer progression in such patients. Ethanol increased the secretion of CCL5 in two CRC cell lines, HT29 and DLD-1. Treatment with CCL5 directly increased migratory ability of these cells, whereas neutralization or knockdown of CCL5 can partially block alcohol-stimulated migration. We further investigated underlying mechanism of CCL5-induced migration. Our results indicated that effects of CCL5 on migration are mediated by the ability of CCL5 to induce autophagy, a cellular process known to be critical for migration. Using high-throughput sequencing and western blotting, we found induction of autophagy by CCL5 takes place via AMPK pathway. Aforementioned ethanol increases CCL5 secretion, CCL5 activates autophagy through AMPK pathway, and autophagy increases migration was confirmed by experiments with autophagy or AMPK inhibitors. To sum up, our study demonstrates that chronic alcohol consumption may promote metastasis of CRC through CCL5-induced autophagy.	[Zhao, Haodong; Chen, Danlei; Cao, Rui; Wang, Shiqing; Yu, Dandan; Liu, Yakun; Jiang, Yu; Wang, Siying] Anhui Med Univ, Sch Basic Med, Dept Pathophysiol, Hefei 230032, Anhui, Peoples R China; [Xu, Mei; Luo, Jia] Univ Kentucky, Coll Med, Dept Pharmacol & Nutr Sci, Lexington, KY 40536 USA		Wang, SY (corresponding author), Anhui Med Univ, Sch Basic Med, Dept Pathophysiol, Hefei 230032, Anhui, Peoples R China.; Luo, J (corresponding author), Univ Kentucky, Coll Med, Dept Pharmacol & Nutr Sci, Lexington, KY 40536 USA.	jialuo888@uky.edu; sywang@ahmu.edu.cn		Luo, Jia/0000-0002-6968-3618			Aldinucci D, 2011, BRIT J HAEMATOL, V152, P182, DOI 10.1111/j.1365-2141.2010.08497.x; Baan R, 2007, LANCET ONCOL, V8, P292, DOI 10.1016/S1470-2045(07)70099-2; Boeing H, 2002, IARC Sci Publ, V156, P151; Cambien B, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0028842; Carling D, 2011, NAT CHEM BIOL, V7, P512, DOI [10.1038/NCHEMBIO.610, 10.1038/nchembio.610]; Chan KK, 2010, WORLD J SURG ONCOL, V8, DOI 10.1186/1477-7819-8-82; Chang LY, 2012, CANCER RES, V72, P1092, DOI 10.1158/0008-5472.CAN-11-2493; Chow MT, 2014, CANCER IMMUNOL RES, V2, P1125, DOI 10.1158/2326-6066.CIR-14-0160; Egan DF, 2011, AUTOPHAGY, V7, P645, DOI 10.4161/auto.7.6.15123; Ferlay J, 2015, INT J CANCER, V136, pE359, DOI 10.1002/ijc.29210; Green DR, 2014, CELL, V157, P65, DOI 10.1016/j.cell.2014.02.049; Hardie DG, 2011, BIOCHEM SOC T, V39, P1, DOI 10.1042/BST0390001; Hegg CC, 2000, NEUROSCIENCE, V98, P191, DOI 10.1016/S0306-4522(00)00101-9; Hutchins Andrew Paul, 2014, Cell Regen, V3, P1, DOI 10.1186/2045-9769-3-1; Indelicato M, 2010, J CELL PHYSIOL, V223, P359, DOI 10.1002/jcp.22041; Kato T, 2013, CYTOKINE, V64, P251, DOI 10.1016/j.cyto.2013.06.313; Kim J, 2011, NAT CELL BIOL, V13, P132, DOI 10.1038/ncb2152; Kroemer G, 2015, J CLIN INVEST, V125, P1, DOI 10.1172/JCI78652; Levine B, 2008, CELL, V132, P27, DOI 10.1016/j.cell.2007.12.018; Long HX, 2012, STEM CELLS, V30, P2309, DOI 10.1002/stem.1194; Lu YM, 2014, ONCOL LETT, V8, P673, DOI 10.3892/ol.2014.2146; Macintosh RL, 2012, CELL CYCLE, V11, P2022, DOI 10.4161/cc.20424; Maltby J, 1996, HEPATOLOGY, V24, P1156; Martinez-Outschoorn UE, 2011, CELL CYCLE, V10, P1784, DOI 10.4161/cc.10.11.15674; McKay A, 2014, WORLD J SURG ONCOL, V12, DOI 10.1186/1477-7819-12-370; Miller KD, 2016, CA-CANCER J CLIN, V66, P271, DOI 10.3322/caac.21349; Mizushima N, 2010, NAT CELL BIOL, V12, P823, DOI 10.1038/ncb0910-823; Moller C, 2003, LEUKEMIA, V17, P203, DOI 10.1038/sj.leu.2402717; Peng YF, 2013, AUTOPHAGY, V9, P2056, DOI 10.4161/auto.26398; Pflaum T, 2016, ARCH TOXICOL, V90, P2349, DOI 10.1007/s00204-016-1770-3; Phi JH, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0169714; Pike KA, 2014, SCI SIGNAL, V7, DOI 10.1126/scisignal.2005020; Pritchard MT, 2005, ALCOHOL CLIN EXP RES, V29, p146S, DOI 10.1097/01.alc.0000189286.81943.51; Rehm J, 2010, ADDICTION, V105, P817, DOI 10.1111/j.1360-0443.2010.02899.x; Ridley AJ, 2003, SCIENCE, V302, P1704, DOI 10.1126/science.1092053; Roberson R, 2012, AM J OBSTET GYNECOL, V207, DOI 10.1016/j.ajog.2012.10.005; Ruiz Rossana, 2016, Rev. gastroenterol. 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J	Zhao, PM; Aguilar, AE; Lee, JY; Paul, LA; Suh, JH; Puri, L; Zhang, M; Beckstead, J; Witkowski, A; Ryan, RO; Saba, JD				Zhao, Piming; Aguilar, Ana E.; Lee, Joanna Y.; Paul, Lucy A.; Suh, Jung H.; Puri, Latika; Zhang, Meng; Beckstead, Jennifer; Witkowski, Andrzej; Ryan, Robert O.; Saba, Julie D.			Sphingadienes show therapeutic efficacy in neuroblastoma in vitro and in vivo by targeting the AKT signaling pathway	INVESTIGATIONAL NEW DRUGS			English	Article						Sphingadienes; Sphingolipids; Neuroblastoma; PI3K; AKT; Nanoparticle	BONE-MARROW-TRANSPLANTATION; CHEMOPREVENTIVE SPHINGADIENES; AMPHOTERICIN-B; COLON-CANCER; CELL-DEATH; SPHINGOLIPIDS; CERAMIDE; SPHINGOSINE-1-PHOSPHATE; EXPRESSION; APOPTOSIS	Neuroblastoma is a childhood malignancy that accounts for approximately 15% of childhood cancer deaths. Only 20-35% of children with metastatic neuroblastoma survive with standard therapy. Identification of more effective therapies is essential to improving the outcome of children with high-stage disease. Sphingadienes (SD) are growth-inhibitory sphingolipids found in natural sources including soy. They exhibit chemopreventive activity in mouse models of colon cancer, where they mediate cytotoxicity by inhibiting key pro-carcinogenic signaling pathways. In this study, the effect of SD on neuroblastoma was analyzed. Low micromolar concentrations of SD were cytotoxic to transformed and primary neuroblastoma cells independently of N-Myc amplification status. SD induced both caspase-dependent apoptosis and autophagy in neuroblastoma cells. However, only inhibition of caspase-dependent apoptosis protected neuroblastoma cells from SD-mediated cytotoxicity. SD also inhibited AKT activation in neuroblastoma cells as shown by reduced phosphorylated AKT levels. Pre-treatment with insulin attenuated SD-mediated cytotoxicity in vitro. SD-loaded nanoparticles (NP) administered parenterally to immunodeficient mice carrying neuroblastoma xenografts resulted in cytotoxic levels of SD in the circulation and significantly reduced tumor growth compared to vehicle-treated controls. Analysis of tumor extracts demonstrated reduced AKT activation in tumors of mice treated with SD-NP compared to controls treated with empty NP. Our findings indicate SD are novel potential chemotherapeutic agents that promote neuroblastoma cell death and reduce tumorigenicity in vivo.	[Zhao, Piming; Aguilar, Ana E.; Lee, Joanna Y.; Paul, Lucy A.; Suh, Jung H.; Puri, Latika; Zhang, Meng; Beckstead, Jennifer; Witkowski, Andrzej; Ryan, Robert O.; Saba, Julie D.] Childrens Hosp, Oakland Res Inst, UCSF Benioff Childrens Hosp Oakland, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA; [Aguilar, Ana E.] Arnold Palmer Hosp Children, 92 W Miller St MP 318 2nd floor, Orlando, FL 32806 USA; [Puri, Latika] St Jude Childrens Res Hosp, 262 Danny Thomas Pl, Memphis, TN 38105 USA		Saba, JD (corresponding author), Childrens Hosp, Oakland Res Inst, UCSF Benioff Childrens Hosp Oakland, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA.	jsaba@chori.org	Puri, Latika/N-8120-2018	Witkowski, Andrzej/0000-0002-0442-4586	St. Baldricks Fellowship [245216]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R37 HL-64159, R01CA129438, S10OD018070]; Swim Across America Foundation; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA129438] Funding Source: NIH RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R37HL064159] Funding Source: NIH RePORTER; OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [S10OD018070] Funding Source: NIH RePORTER	This study was supported by St. Baldricks Fellowship Grant 245216 (AEA), National Institutes of Health grants R01CA129438, S10OD018070 and Swim Across America Foundation (JDS) and National Institutes of Health grant R37 HL-64159 (ROR).	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New Drugs	OCT	2018	36	5					743	754		10.1007/s10637-017-0558-5			12	Oncology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	GT4LI	WOS:000444475200001	29335887	Green Accepted			2022-04-25	
J	Lee, S; Hallis, SP; Jung, KA; Ryu, D; Kwak, MK				Lee, Sujin; Hallis, Steffanus Pranoto; Jung, Kyeong-Ah; Ryu, Dayoung; Kwak, Mi-Kyoung			Impairment of HIF-1 alpha-mediated metabolic adaption by NRF2-silencing in breast cancer cells	REDOX BIOLOGY			English	Article						Hypoxia; Metabolism; Autophagy; HIF-1 alpha; NFE2L2/NRF2; Metabolome	HYPOXIA-INDUCIBLE FACTORS; AUTOPHAGY; INDUCTION; KINASE; BNIP3; MITOCHONDRIA; EXPRESSION; RESPONSES; OXYGEN; HIF-1	Hypoxia, a common element in the tumor environment, leads to Hypoxia-Inducible Factor-1 alpha (HIF-1 alpha) stabilization to modulate cellular metabolism as an adaptive response. In a previous study, we showed that inhibition of the nuclear factor erythroid 2-like-2 (NFE2L2; NRF2), a master regulator of many genes coping with electrophilic and oxidative stress, elevated the level of miR-181c and induced mitochondrial dysfunction in colon cancer cells. In this study, we demonstrate that NRF2-silencing hindered HIF-1 alpha accumulation in hypoxic breast cancer cells and subsequently suppressed hypoxia-inducible expression of glycolysis-associated glucose transporter-1, hexokinase-2, pyruvate dehydrogenase kinase-1, and lactate dehydrogenase A. HIF-1 alpha dysregulation in NRF2-silenced cancer cells was associated with miR-181c elevation. Overexpression of miR-181c in breast cancer cells blocked HIF-1 alpha accumulation and diminished hypoxia-inducible levels of glycolysis enzymes, whereas the inhibition of miR-181c in NRF2-silenced cells restored HIF-1 alpha accumulation. In a subsequent metabolomic analysis, hypoxic incubation increased the levels of metabolites involved in glycolysis and activated the pentose phosphate pathway (PPP) in control cells. However, these elevations were less pronounced in NRF2-silenced cells. In particular, hypoxic incubation increased the levels of amino acids, which implies a shift to catabolic metabolism, and the increased levels were higher in control cells than in NRF2-silenced cells. Concurrently, hypoxia activated BCL2 interacting protein 3 (BNIP3)-mediated autophagy in the control cells and tniR-181c was found to be involved in this autophagy activation. Taken together, these results show that hypoxia-induced metabolic changes to glycolysis, the PPP, and autophagy are inhibited by NRF2-silencing through miR-181c-mediated HIF-1 alpha dysregulation. Therefore, targeting NRF2/miR-181c could be an effective strategy to counteract HIF-1 alpha-orchestrated metabolic adaptation of hypoxic cancer cells.	[Lee, Sujin; Hallis, Steffanus Pranoto; Ryu, Dayoung; Kwak, Mi-Kyoung] Catholic Univ Korea, Dept Pharm, Grad Sch, 43 Jibong Ro, Bucheon 14562, Gyeonggi Do, South Korea; [Lee, Sujin; Hallis, Steffanus Pranoto; Ryu, Dayoung; Kwak, Mi-Kyoung] Catholic Univ Korea, BK21PLUS Team Creat Leader Program Pharmac Based, Grad Sch, 43 Jibong Ro, Bucheon 14562, Gyeonggi Do, South Korea; [Hallis, Steffanus Pranoto] Atma Jaya Catholic Univ Indonesia, Fac Biotechnol, Jakarta 12930, Indonesia; [Jung, Kyeong-Ah; Kwak, Mi-Kyoung] Catholic Univ Korea, Integrated Res Inst Pharmaceut Sci, Bucheon, Gyeonggi Do, South Korea; [Kwak, Mi-Kyoung] Catholic Univ Korea, Coll Pharm, 43 Jibong Ro, Bucheon 14662, Gyeonggi Do, South Korea		Kwak, MK (corresponding author), Catholic Univ Korea, Coll Pharm, 43 Jibong Ro, Bucheon 14662, Gyeonggi Do, South Korea.	mkwak@catholic.ac.kr		Hallis, Steffanus Pranoto/0000-0002-8841-4835	National Research Foundation of Korea (NRF) - Korea government (MSIP) [2018R1A2A1A05078894, 2015R1A2A1A10054384, 2018R1A6A1A03025108]; BK21Plus grant of NRF - Korean government [22A20130012250]	This study was financially supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korea government (MSIP) (2018R1A2A1A05078894, 2015R1A2A1A10054384, and 2018R1A6A1A03025108). This study was also supported by the BK21Plus grant of NRF funded by Korean government (22A20130012250).	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J	Peixoto, P; Castronovo, V; Matheus, N; Polese, C; Peulen, O; Gonzalez, A; Boxus, M; Verdin, E; Thiry, M; Dequiedt, F; Mottet, D				Peixoto, P.; Castronovo, V.; Matheus, N.; Polese, C.; Peulen, O.; Gonzalez, A.; Boxus, M.; Verdin, E.; Thiry, M.; Dequiedt, F.; Mottet, D.			HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells	CELL DEATH AND DIFFERENTIATION			English	Article						histone deacetylases; cancer cells; siRNA; autophagy; cell proliferation; chemotherapy	II HISTONE DEACETYLASES; S-PHASE PROGRESSION; DNA-REPLICATION; MAMMALIAN-CELLS; COLON-CANCER; CHECKPOINT; EXPRESSION; PROTEINS; COMPLEX; GROWTH	Histone deacetylases (HDACs) form a family of enzymes, which have fundamental roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation, and apoptosis of cancer cells. In this study, we further investigated the biological function of HDAC5 in cancer cells. We found HDAC5 is associated with actively replicating pericentric heterochromatin during late S phase. We demonstrated that specific depletion of HDAC5 by RNA interference resulted in profound changes in the heterochromatin structure and slowed down ongoing replication forks. This defect in heterochromatin maintenance and assembly are sensed by DNA damage checkpoint pathways, which triggered cancer cells to autophagy and apoptosis, and arrested their growth both in vitro and in vivo. Finally, we also demonstrated that HDAC5 depletion led to enhanced sensitivity of DNA to DNA-damaging agents, suggesting that heterochromatin de-condensation induced by histone HDAC5 silencing may enhance the efficacy of cytotoxic agents that act by targeting DNA in vitro. Together, these results highlighted for the first time an unrecognized link between HDAC5 and the maintenance/assembly of heterochromatin structure, and demonstrated that its specific inhibition might contribute to increase the efficacy of DNA alteration-based cancer therapies in clinic. Cell Death and Differentiation (2012) 19, 1239-1252; doi: 10.1038/cdd.2012.3; published online 3 February 2012	[Mottet, D.] Univ Liege, Metastasis Res Lab, GIGA Canc, B-4000 Liege, Belgium; [Boxus, M.] Gembloux Agro Biotech GxABT, Cellular & Mol Biol Unit, B-5030 Gembloux, Belgium; [Verdin, E.] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA; [Thiry, M.] Univ Liege, Fac Sci, Dept Life Sci, Cell Biol Lab, B-4000 Liege, Belgium; [Dequiedt, F.] Univ Liege, Lab Signalisat & Interact Prote PSI, B-4000 Liege, Belgium; [Peixoto, P.; Castronovo, V.; Matheus, N.; Polese, C.; Peulen, O.; Gonzalez, A.; Thiry, M.; Dequiedt, F.; Mottet, D.] Univ Liege, Interdisciplinary Cluster Appl Genoprote GIGA, B-4000 Liege, Belgium		Mottet, D (corresponding author), Univ Liege, Metastasis Res Lab, GIGA Canc, Pathol Bldg,B23,4, B-4000 Liege, Belgium.	dmottet@ulg.ac.be	Verdin, Eric/AAB-7999-2019; Peulen, Olivier/C-1250-2018	Peulen, Olivier/0000-0002-6933-0134; Peixoto, Paul/0000-0001-6302-7823; Verdin, Eric/0000-0003-3703-3183; Dequiedt, Franck/0000-0003-1234-7477	National Fund for Scientific Research (FNRS) (Belgium)Fonds de la Recherche Scientifique - FNRS; Centre Anti-Cancereux pres de l'Universite de Liege; Fonds Leon Fredericq; TELEVIE; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [P30AI027763] Funding Source: NIH RePORTER	This work was supported by grants from the National Fund for Scientific Research (FNRS) (Belgium), the Centre Anti-Cancereux pres de l'Universite de Liege, the Fonds Leon Fredericq, and TELEVIE. D Mottet and F Dequiedt are Research Associates at the National Fund for Scientific Research (FNRS). M Boxus is Postdoctoral Researcher at the FNRS. N Matheus is an FRIA Fellow. A Gonzalez is TELEVIE Fellow. We thank Dr D DiPaola for expert advice on the nascent-strand DNA abundance assay.	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JUL	2012	19	7					1239	1252		10.1038/cdd.2012.3			14	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	959EJ	WOS:000305295300015	22301920	Green Published, Bronze			2022-04-25	
J	Alves-Fernandes, DK; Jasiulionis, MG				Alves-Fernandes, Debora Kristina; Jasiulionis, Miriam Galvonas			The Role of SIRT1 on DNA Damage Response and Epigenetic Alterations in Cancer	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						SIRT1; DNA damage; repair; epigenetics; cancer development	OXIDATIVE STRESS; WERNER-SYNDROME; HISTONE H2AX; GENOMIC STABILITY; TUMOR-SUPPRESSOR; REACTIVE OXYGEN; REPAIR PROTEINS; EXCISION-REPAIR; DEACETYLATION; GENE	Sirtuin-1 (SIRT1) is a class-III histone deacetylase (HDAC), an NAD+-dependent enzyme deeply involved in gene regulation, genome stability maintenance, apoptosis, autophagy, senescence, proliferation, aging, and tumorigenesis. It also has a key role in the epigenetic regulation of tissue homeostasis and many diseases by deacetylating both histone and non-histone targets. Different studies have shown ambiguous implications of SIRT1 as both a tumor suppressor and tumor promoter. However, this contradictory role seems to be determined by the cell type and SIRT1 localization. SIRT1 upregulation has already been demonstrated in some cancer cells, such as acute myeloid leukemia (AML) and primary colon, prostate, melanoma, and non-melanoma skin cancers, while SIRT1 downregulation was described in breast cancer and hepatic cell carcinomas. Even though new functions of SIRT1 have been characterized, the underlying mechanisms that define its precise role on DNA damage and repair and their contribution to cancer development remains underexplored. Here, we discuss the recent findings on the interplay among SIRT1, oxidative stress, and DNA repair machinery and its impact on normal and cancer cells.	[Alves-Fernandes, Debora Kristina; Jasiulionis, Miriam Galvonas] Univ Fed Sao Paulo, Escola Paulista Med, Dept Pharmacol, BR-04039032 Sao Paulo, Brazil		Jasiulionis, MG (corresponding author), Univ Fed Sao Paulo, Escola Paulista Med, Dept Pharmacol, BR-04039032 Sao Paulo, Brazil.	mjasiulionis@gmail.com	Jasiulionis, Miriam/G-2207-2012; Alves-Fernandes, Debora Kristina/AAC-5983-2019; Alves-Fernandes, Débora Kristina/AAQ-3385-2020	Jasiulionis, Miriam/0000-0002-4135-0440; Alves-Fernandes, Débora Kristina/0000-0002-0917-9292	FAPESPFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); CNPqConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [400036/2016-9]; CAPESCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (Capes)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [001]	This research was funded by FAPESP, CNPq (grant number 400036/2016-9) and CAPES (Post-Doctoral Fellow)". This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (Capes)-Finance Code 001.	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J. Mol. Sci.	JUL 1	2019	20	13							3153	10.3390/ijms20133153			13	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	IL1EG	WOS:000477041100041	31261609	Green Submitted, Green Published, gold			2022-04-25	
J	Dai, XY; Zhou, BF; Xie, YY; Lou, J; Li, KQ				Dai, Xiao-Yu; Zhou, Bao-Feng; Xie, Yang-Yang; Lou, Jie; Li, Ke-Qiang			Bufalin and 5-fluorouracil synergistically induce apoptosis in colorectal cancer cells	ONCOLOGY LETTERS			English	Article						colorectal cancer; 5-fluorouracil; bufalin; apoptosis; B-cell lymphoma-2-associated X protein	HEPATOCELLULAR-CARCINOMA; OSTEOSARCOMA CELLS; CYCLE ARREST; LUNG-CANCER; STEM-CELLS; CHEMOTHERAPY; ACTIVATION; MECHANISMS; AUTOPHAGY; PATHWAYS	5-fluorouracil (5-FU) has been used in the treatment of colorectal cancer for >50 years. However, drug resistance remains an obstacle in the application of 5-FU-based chemotherapy. Bufalin, a type of steroid with anti-tumor activity, may be purified from the skin and parotid venom glands of toads. In order to improve the anti-tumor effect of 5-FU, the present study examined the combined effects of bufalin with 5-FU on human colorectal cancer HCT116 cells. Following treatment, cell proliferation was quantified using MIT assay and apoptotic cell percentage was assessed by flow cytometry. The apoptosis-associated protein expression was evaluated by western blotting. It was observed that bufalin enhanced the cytotoxicity of 5-FU in HCT116 cells via the induction of the mitochondria' apoptotic pathway. Additionally, bufalin combined with 5-FU reduced the expression levels of anti-apoptotic proteins, such as Mcl-1, XIAP and Bcl-2 and upregulated the levels of the pro-apoptotic proteins, Bax and Bad. To verify the role of Bax, RNA interference was used to knock-down Bax. It was determined that the synergistic effect between 5-FU and bufalin was diminished following the silencing of Bax. In summary, bufalin in combination with 5-FU may induce a higher level of apoptosis compared with monotherapy, and the combination mat be a potential therapeutic strategy for the treatment of colorectal cancer.	[Dai, Xiao-Yu; Zhou, Bao-Feng; Xie, Yang-Yang] Ningbo 2 Hosp, Clin Res Ctr, Dept Anorectal Surg, 41 Xibei Rd, Ningbo 315010, Zhejiang, Peoples R China; [Lou, Jie] Ningbo 2 Hosp, Clin Res Ctr, Dept Digest, Ningbo 315010, Zhejiang, Peoples R China; [Li, Ke-Qiang] Ningbo 2 Hosp, Clin Res Ctr, Key Lab Mol Biol Canc, 41 Xibei Rd, Ningbo 315010, Zhejiang, Peoples R China		Dai, XY (corresponding author), Ningbo 2 Hosp, Clin Res Ctr, Dept Anorectal Surg, 41 Xibei Rd, Ningbo 315010, Zhejiang, Peoples R China.; Li, KQ (corresponding author), Ningbo 2 Hosp, Clin Res Ctr, Key Lab Mol Biol Canc, 41 Xibei Rd, Ningbo 315010, Zhejiang, Peoples R China.	daixiaoyu0106@126.com; likeqiang1264@163.com			Natural Science Foundation of Ningbo [2014A610225]; Medical Foundation of Ningbo [211B10]; Social Development and Scientific and Technological Projects Foundation of Ningbo [2014C50068]; Huamei Foundation of Ningbo; Huamei Foundation of Ningbo No. 2 Hospital [2015HMKY07, 2015HMKY08, 2015HMKY36]	The present study was supported by grants from the Natural Science Foundation of Ningbo (grant no. 2014A610225), Medical Foundation of Ningbo (grant no. 211B10), Social Development and Scientific and Technological Projects Foundation of Ningbo (grant no. 2014C50068), Huamei Foundation of Ningbo No. 2 Hospital (grant nos. 2015HMKY07, 2015HMKY08 and 2015HMKY36).	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Lett.	MAY	2018	15	5					8019	8026		10.3892/ol.2018.8332			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GF3DN	WOS:000431825900253	29849804	gold, Green Published			2022-04-25	
J	Kim, YS; Shin, JH; Bae, MK; Lee, CY; Kim, DJ; Chung, KY; Lee, JG				Kim, Young Sam; Shin, Ju Hye; Bae, Mi Kyung; Lee, Chang Young; Kim, Dae Joon; Chung, Kyung Young; Lee, Jin Gu			Autophagy Activity in Pulmonary Metastatic Tumor Tissues from Colorectal Cancer: A Pilot Study	YONSEI MEDICAL JOURNAL			English	Article						Colorectal cancer; metastasis; treatment failure; autophagy	DOUBLE-EDGED-SWORD; CELL-SURVIVAL; APOPTOSIS	Purpose: Autophagy has been reported to be involved in treatment failure in tumor. We aimed to evaluate autophagy activity in tumor tissue and compare them between the recurrence and non-recurrence groups. Materials and Methods: We analyzed expressions of autophagy-related proteins in tumor tissues which were obtained from pulmonary metastases of colorectal cancer patients by Western blot. We also analyzed autophagosomes by transmission electron microscopy. Results: Tumor tissues from recurrence group showed increased levels of LC3B-II, decreased levels of p62/SQSTM1, and also a marked accumulation of autophagosomes compared with tissues from non-recurrence group. Conclusion: The present study suggests that autophagy may be associated with treatment failure of metastatic colorectal cancer.	[Kim, Young Sam; Shin, Ju Hye] Yonsei Univ, Coll Med, Dept Internal Med, Seoul 120752, South Korea; [Bae, Mi Kyung; Lee, Chang Young; Kim, Dae Joon; Chung, Kyung Young; Lee, Jin Gu] Yonsei Univ, Coll Med, Dept Thorac & Cardiovasc Surg, Seoul 120752, South Korea		Lee, JG (corresponding author), Yonsei Univ, Coll Med, Dept Thorac & Cardiovasc Surg, 50-1 Yonsei Ro, Seoul 120752, South Korea.	csjglee@yuhs.ac		Kim, Young Sam/0000-0001-9656-8482	Bumsuk Academic Research Fund	This paper was supported by Bumsuk Academic Research Fund in 2012.	Abedin MJ, 2007, CELL DEATH DIFFER, V14, P500, DOI 10.1038/sj.cdd.4402039; Chao YK, 2012, THORAC CARDIOV SURG, V60, P398, DOI 10.1055/s-0031-1295574; Chen N, 2009, BBA-MOL CELL RES, V1793, P1516, DOI 10.1016/j.bbamcr.2008.12.013; Degenhardt K, 2006, CANCER CELL, V10, P51, DOI 10.1016/j.ccr.2006.06.001; Eadens MJ, 2011, CURR ONCOL REP, V13, P168, DOI 10.1007/s11912-011-0157-0; Johansen T, 2011, AUTOPHAGY, V7, P279, DOI 10.4161/auto.7.3.14487; Katayama M, 2007, CELL DEATH DIFFER, V14, P548, DOI 10.1038/sj.cdd.4402030; Klionsky DJ, 2008, AUTOPHAGY, V4, P151, DOI 10.4161/auto.5338; Lum JJ, 2005, CELL, V120, P237, DOI 10.1016/j.cell.2004.11.046; Maiuri MC, 2007, NAT REV MOL CELL BIO, V8, P741, DOI 10.1038/nrm2239; Marx J, 2006, SCIENCE, V312, P1160, DOI 10.1126/science.312.5777.1160; Mathew R, 2007, NAT REV CANCER, V7, P961, DOI 10.1038/nrc2254; Papandreou I, 2008, CELL DEATH DIFFER, V15, P1572, DOI 10.1038/cdd.2008.84; Sato K, 2007, CANCER RES, V67, P9677, DOI 10.1158/0008-5472.CAN-07-1462; Shintani T, 2004, SCIENCE, V306, P990, DOI 10.1126/science.1099993; White E, 2009, CLIN CANCER RES, V15, P5308, DOI 10.1158/1078-0432.CCR-07-5023; Zheng Hai-yang, 2012, Cancer Biology Medicine, V9, P105, DOI 10.3969/j.issn.2095-3941.2012.02.004	17	6	6	0	4	YONSEI UNIV COLL MEDICINE	SEOUL	50-1 YONSEI-RO, SEODAEMUN-GU, SEOUL 120-752, SOUTH KOREA	0513-5796	1976-2437		YONSEI MED J	Yonsei Med. J.	NOV 1	2014	55	6					1484	1488		10.3349/ymj.2014.55.6.1484			5	Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	General & Internal Medicine	AR7UL	WOS:000343785100004	25323883	Green Published, Green Submitted, gold			2022-04-25	
J	He, K; Wu, L; Ding, QS; Haider, F; Yu, HG; Wang, HH; Xiang, GA				He, Ke; Wu, Lu; Ding, Qianshan; Haider, Farhan; Yu, Honggang; Wang, Haihe; Xiang, Guoan			Apatinib Promotes Apoptosis of Pancreatic Cancer Cells through Downregulation of Hypoxia-Inducible Factor-1 alpha and Increased Levels of Reactive Oxygen Species	OXIDATIVE MEDICINE AND CELLULAR LONGEVITY			English	Article							TYROSINE KINASE; COLON-CANCER; AUTOPHAGY; INHIBITOR; GROWTH	At present, apatinib is considered a new generation agent for the treatment of patients with gastric cancer. However, the effects of apatinib on pancreatic cancer have not been clarified. This study investigated the impact of apatinib on the biological function of pancreatic cancer cells and the potential mechanism involved in this process. Using the Cell Counting Kit-8 method, we confirmed that apatinib treatment inhibited cell proliferation in vitro. Moreover, the migration rate of pancreatic cells was inhibited. The effects of apatinib on apoptosis and cell cycle distribution of pancreatic carcinoma cells were detected by flow cytometry. The number of apoptotic cells was significantly increased, and the cell cycle was altered. Furthermore, we demonstrated that apatinib inhibited the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor, and markers of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathway, which increased the levels of reactive oxygen species in vitro. Apatinib significantly inhibited the biological function of pancreatic cancer cells. It promoted apoptosis, downregulated the expression of HIF-1 alpha, and increased the levels of reactive oxygen species.	[He, Ke; Haider, Farhan; Wang, Haihe] Sun Yat Sen Univ, Dept Biochem, Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China; [He, Ke; Haider, Farhan; Wang, Haihe] Sun Yat Sen Univ, Ctr Stern Cell Biol & Tissue Engn, Key Lab Minist Educ, Guangzhou 510080, Guangdong, Peoples R China; [He, Ke; Xiang, Guoan] Guangdong Second Prov Gen Hosp, Dept Gen Surg, Guangzhou 510317, Guangdong, Peoples R China; [Wu, Lu] Wuhan Univ, Zhongnan Hosp, Dept Radiat & Med Oncol, Wuhan 430071, Hubei, Peoples R China; [Wu, Lu; Ding, Qianshan; Yu, Honggang] Wuhan Univ, Dept Gastroenterol, Renmin Hosp, Wuhan 430060, Hubei, Peoples R China; [Wu, Lu] Wuhan Univ, Dept Radiat & Med Oncol, Hubei Key Lab Tumor Biol Behav, Hubei Clin Canc Study Ctr,Zhongnan Hosp, Wuhan 430071, Hubei, Peoples R China		Wang, HH (corresponding author), Sun Yat Sen Univ, Dept Biochem, Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China.; Wang, HH (corresponding author), Sun Yat Sen Univ, Ctr Stern Cell Biol & Tissue Engn, Key Lab Minist Educ, Guangzhou 510080, Guangdong, Peoples R China.; Xiang, GA (corresponding author), Guangdong Second Prov Gen Hosp, Dept Gen Surg, Guangzhou 510317, Guangdong, Peoples R China.	wanghaih@mail.sysu.edu.cn; guoan_66@163.com	Haihe, Wang/AAD-4036-2021	, Haihe/0000-0002-9302-2334; He, Ke/0000-0002-9194-8408	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81071990, 81641110]; Natural Science Foundation of Guangdong Province, ChinaNational Natural Science Foundation of Guangdong Province [2015A030313725]; Science and Technology Program of Guangdong Province, China [201707010305]; Medical Research Foundation of Guangdong Province, China [A2017427]; Youth Science Foundation of Guangdong Second Provincial General Hospital [YQ2016-001]	The authors would like to thank Dr. Liu Fei and Mr. Xia Hong for their excellent technical assistance in this work. This work was supported by grants from the National Natural Science Foundation of China (nos. 81071990 and 81641110), the Natural Science Foundation of Guangdong Province, China (no. 2015A030313725), the Science and Technology Program of Guangdong Province, China (no. 201707010305), the Medical Research Foundation of Guangdong Province, China (no. A2017427), and the Youth Science Foundation of Guangdong Second Provincial General Hospital (no. YQ2016-001).	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J	Wang, LJ; Yu, ZX; Wei, C; Zhang, L; Song, H; Chen, B; Yang, QF				Wang, Lijuan; Yu, Zhongxia; Wei, Chao; Zhang, Li; Song, Hui; Chen, Bing; Yang, Qifeng			Huaier aqueous extract protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NLRP3 inflammasome activation	ONCOTARGET			English	Article						Huaier; colitis; NLRP3; inflammasome; IL-1 beta	INTESTINAL INFLAMMATION; ULCERATIVE-COLITIS; BOWEL-DISEASE; BREAST-CANCER; CELLS; POLYSACCHARIDE; PROLIFERATION; APOPTOSIS; PATHWAY	The use of Trametes robiniophila Murr. (Huaier) as a complementary therapy for cancer has recently become increasingly common in China. However, whether Huaier can regulate host immune responses, especially innate immunity, remains largely unknown. The NLRP3 inflammasome is a multimeric complex consisting of NLRP3, ASC and caspase-1. NLRP3 inflammasomes respond to a variety of endogenous (damage-associated molecular patterns) and exogenous (pathogen-associated molecular patterns) stimuli, and play crucial roles in host defense against pathogens and multiple diseases such as ulcerative colitis (UC). In this study, we investigated the anti-inflammatory effect of Huaier in dextran sulfate sodium (DSS)-induced murine colitis and revealed the underlying mechanisms by targeting NLRP3 inflammasomes. In C57BL/6 mice, oral administration of Huaier attenuated DSS-induced colon shortening and colonic pathological damage. Furthermore, we analyzed the effect of Huaier on NLRP3 inflammasome activation in macrophages. Huaier inhibited NLRP3 inflammasome activation-induced IL-1 beta secretion and caspase-1 cleavage. Moreover, Huaier decreased NLRP3 protein expression via promoting NLRP3 degradation through the autophagy lysosome pathway. Therefore, our findings demonstrate a novel function for Huaier in the regulation of NLRP3 inflammasome activation and suggest a potential role for Huaier in NLRP3 inflammasome-associated diseases.	[Wang, Lijuan; Zhang, Li; Chen, Bing; Yang, Qifeng] Shandong Univ, Qilu Hosp, Pathol Tissue Bank, Jinan 250012, Shandong, Peoples R China; [Yu, Zhongxia; Song, Hui] Shandong Univ, Dept Immunol, Sch Med, Jinan 250012, Shandong, Peoples R China; [Yu, Zhongxia; Song, Hui] Shandong Univ, Key Lab Infect & Immun Shandong Prov, Sch Med, Jinan 250012, Shandong, Peoples R China; [Wei, Chao] Shandong Univ, Hosp 2, Dept Ophthalmol, Jinan 250033, Shandong, Peoples R China; [Zhang, Li; Yang, Qifeng] Shandong Univ, Qilu Hosp, Dept Breast Surg, Jinan 250012, Shandong, Peoples R China		Yang, QF (corresponding author), Shandong Univ, Qilu Hosp, Pathol Tissue Bank, Jinan 250012, Shandong, Peoples R China.; Yang, QF (corresponding author), Shandong Univ, Qilu Hosp, Dept Breast Surg, Jinan 250012, Shandong, Peoples R China.	qifengy_sdu@163.com		Yang, Qifeng/0000-0003-0576-8513	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31500699]; Foundation for Excellent Young Scientist of Shandong Province [BS2015WS002, BS2015SW005]; Science Foundation of Qilu Hospital of Shandong University [2015QLQN24]; Fundamental Research Funds of Shandong University [2016JC023]	This work was supported by grants from the National Natural Science Foundation of China (31500699), the Foundation for Excellent Young Scientist of Shandong Province (BS2015WS002), the Foundation for Excellent Young Scientist of Shandong Province (BS2015SW005), the Science Foundation of Qilu Hospital of Shandong University(2015QLQN24), and the Fundamental Research Funds of Shandong University (2016JC023).	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J	Zhang, DD; Gao, CX; Li, RY; Zhang, L; Tian, JK				Zhang, Dandan; Gao, Cuixia; Li, Ruyi; Zhang, Lin; Tian, Jingkui			TEOA, a triterpenoid from Actinidia eriantha, induces autophagy in SW620 cells via endoplasmic reticulum stress and ROS-dependent mitophagy	ARCHIVES OF PHARMACAL RESEARCH			English	Article						Actinidia eriantha root; TEOA; SW620; Autophagy; ER stress; Mitophagy	UNFOLDED PROTEIN RESPONSE; OXIDATIVE STRESS; PARKIN; PERK; NIX; SURVIVAL; DISEASE; GLUCOSE; PINK1; PHOSPHORYLATION	2 alpha,3 alpha,24-Thrihydroxyurs-12-en-28-oicacid (TEOA), a pentacyclic triterpenoid, isolated from the roots of Actinidia eriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, we investigated the underlying molecular mechanism of the anticancer activity of TEOA in SW620 cells. We demonstrated that TEOA induced apoptosis through cleavage of caspase-9 and PARP in SW620 cells. In addition, evidence of TEOA-mediated autophagy included the induction of autophagolysosomes and activation of autophagic markers LC-3B and p62. Further analysis illustrated that TEOA promoted the phosphorylation of PERK and elF2 alpha, followed by up-regulation of the downstream protein CHOP, suggesting the involvement of PERK/eIF2 alpha/CHOP pathway and ER stress in TEOA-induced autophagy in SW620 cells. Meanwhile, TEOA-mediated PINK1, Parkin, ubiquitin and p62 activation revealed that TEOA induced specific autophagy-mitophagy in SW620 cells. Additionally, an antioxidant NAC attenuated the TEOA-induced mitophagy, indicating that TEOA triggers mitophagy via a ROS-dependent pathway. Collectively, our findings revealed a novel cellular mechanism of TEOA in the colon cancer cell line SW620, thus providing a molecular basis for developing TEOA into an anti-tumor candidate.	[Zhang, Dandan; Gao, Cuixia; Li, Ruyi; Zhang, Lin; Tian, Jingkui] Zhejiang Univ, Inst Biomed Engn, Coll Biomed Engn & Instrument Sci, Hangzhou, Zhejiang, Peoples R China; [Tian, Jingkui] Zhejiang Univ, Zhejiang Malaysia Joint Res Ctr Tradit Med, Hangzhou, Zhejiang, Peoples R China		Tian, JK (corresponding author), Zhejiang Univ, Inst Biomed Engn, Coll Biomed Engn & Instrument Sci, Hangzhou, Zhejiang, Peoples R China.; Tian, JK (corresponding author), Zhejiang Univ, Zhejiang Malaysia Joint Res Ctr Tradit Med, Hangzhou, Zhejiang, Peoples R China.	tjk@zju.edu.cn			National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81473182]; Jiangsu Provincial Natural Science Foundation of ChinaNatural Science Foundation of Jiangsu Province [BK20161269]; Jiangsu Technology Support Program [BE2014654]	This work was supported by the National Science Foundation of China (Grant No. 81473182), the Jiangsu Provincial Natural Science Foundation of China (Grant No. BK20161269) and the Jiangsu Technology Support Program (Grant No. BE2014654).	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Pharm. Res.	MAY	2017	40	5					579	591		10.1007/s12272-017-0899-9			13	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	EV4IH	WOS:000401721700005	28211011				2022-04-25	
J	Choi, SW; Song, JK; Yim, YS; Yun, HG; Chun, KH				Choi, Seung-Won; Song, Jun-Kyu; Yim, Ye-Seal; Yun, Ho-Geun; Chun, Kyung-Hee			Glucose Deprivation Triggers Protein Kinase C-dependent beta-Catenin Proteasomal Degradation	JOURNAL OF BIOLOGICAL CHEMISTRY			English	Article							GASTRIC-CANCER; COLON-CARCINOMA; MELANOMA-CELLS; BREAST-CANCER; PATHWAY; AUTOPHAGY; WNT; INACTIVATION; SENESCENCE; EXPRESSION	Autophagy is a conserved process that contributes to cell homeostasis. It is well known that induction mainly occurs in response to nutrient starvation, such as starvation of amino acids and insulin, and its mechanisms have been extensively characterized. However, the mechanisms behind cellular glucose deprivation-induced autophagy are as of now poorly understood. In the present study, we determined a mechanism by which glucose deprivation induced the PKC-dependent proteasomal degradation of beta-catenin, leading to autophagy. Glucose deprivation was shown to cause a sub-G(1) transition and enhancement of the LC3-II protein levels, whereas beta-catenin protein underwent degradation in a proteasome-dependent manner. Moreover, the inhibition of GSK3 beta was unable to abolish the glucose deprivation-mediated beta-catenin degradation or up-regulation of LC3-II protein levels, which suggested GSK3 beta-independent protein degradation. Intriguingly, the inhibition of PKC beta using a pharmacological inhibitor and transfection of siRNA for PKC alpha was observed to effectively block glucose deprivation- induced beta-catenin degradation as well as the increase in LC3-II levels and the accumulation of a sub-G(1) population. Together, our results demonstrated a molecular mechanism by which glucose deprivation can induce the GSK3 beta-independent protein degradation of beta-catenin, leading to autophagy.	[Choi, Seung-Won; Song, Jun-Kyu; Yim, Ye-Seal; Yun, Ho-Geun; Chun, Kyung-Hee] Yonsei Univ, Coll Med, Dept Biochem & Mol Biol, 50 Yonsei Ro, Seoul 120752, South Korea; [Song, Jun-Kyu; Yim, Ye-Seal; Yun, Ho-Geun; Chun, Kyung-Hee] Yonsei Univ, Brain Korea Plus Project Med Sci 21, Seoul 120752, South Korea		Chun, KH (corresponding author), Yonsei Univ, Coll Med, Dept Biochem & Mol Biol, 50 Yonsei Ro, Seoul 120752, South Korea.	khchun@yuhs.ac			National Research Foundation of Korea (NRF) - Korean government (Ministry of Science, ICT and Future Planning) [NRF-2014R1A2A1A11050600, NRF-2011-0030086]; Korea Health Technology RAMP;D Project, Ministry of Health and Welfare [A121982]	This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (Ministry of Science, ICT and Future Planning) (Grants NRF-2014R1A2A1A11050600 and NRF-2011-0030086) and by the Korea Health Technology R&D Project, Ministry of Health and Welfare, Grant A121982.	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Biol. Chem.	APR 10	2015	290	15					9863	9873		10.1074/jbc.M114.606756			11	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	CF7IJ	WOS:000352729400045	25691573	Green Published, hybrid			2022-04-25	
J	Zhao, XG; Sun, RJ; Yang, XY; Liu, DY; Lei, DP; Jin, T; Pan, XL				Zhao, Xing-guo; Sun, Rui-jie; Yang, Xiao-yan; Liu, Da-yu; Lei, Da-peng; Jin, Tong; Pan, Xin-liang			Chloroquine-Enhanced Efficacy of Cisplatin in the Treatment of Hypopharyngeal Carcinoma in Xenograft Mice	PLOS ONE			English	Article							CELL LUNG-CANCER; CONCURRENT CHEMORADIOTHERAPY; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; AUTOPHAGY; RESISTANCE; INHIBITION; APOPTOSIS; TUMORIGENESIS; COMBINATION	Hypopharyngeal squamous cell carcinoma (HSCC) has the worst prognosis among head and neck cancers. Cisplatin (DDP)-based chemotherapy is an important part of multimodal treatments. However, resistance to DDP severely impairs the effectiveness of chemotherapy for HSCC. Chloroquine (CQ) has been reported to enhance the effectiveness of chemotherapy and radiotherapy in liver, pancreas, breast, prostate and colon tumors, but it is unclear whether CQ could increase the efficacy of DDP for treating HSCC. We inoculated BALB/c nude mice with a subcutaneous injection of human hypopharyngeal FaDu cells to generate our animal model. Mice were randomly divided into 4 groups and treated with vehicle control, CQ (60 mg/kg/day), DDP (5 mg/kg/6 days), or a combination of DDP and CQ. Tumor growth and survival of the mice were monitored. We found that CQ inhibited autophagy and increased DDP-induced apoptosis in the xenograft mouse model. CQ enhanced the efficacy of DDP, resulting in decreased tumor growth and prolonged survival of the mice. To test whether blocking autophagy enhanced the efficacy of DDP, FaDu cells were infected with lentiviral shRNA to Beclin-1 and inoculated into the flanks of nude mice. Inhibition of autophagy markedly enhanced the DDP-induced antitumor effect. Our study suggests that the addition of CQ to DDP-based chemotherapy could be a potential therapeutic strategy for treating HSCC, and the inhibition of autophagy may contribute to chemotherapy sensitization in HSCC.	[Zhao, Xing-guo; Sun, Rui-jie; Liu, Da-yu; Lei, Da-peng; Jin, Tong; Pan, Xin-liang] Shandong Univ, Qilu Hosp, Dept Otolaryngol, Jinan 250100, Shandong, Peoples R China; [Yang, Xiao-yan] Shandong Univ, Qilu Hosp, Key Lab Cardiovasc Remodeling & Funct Res, Jinan 250100, Shandong, Peoples R China		Pan, XL (corresponding author), Shandong Univ, Qilu Hosp, Dept Otolaryngol, Jinan 250100, Shandong, Peoples R China.	pan_xinl@163.com			Independent Innovation Foundation of Shandong University (IIFSDU) [2012TS156]; Shandong Provincial Natural Science Foundation, ChinaNatural Science Foundation of Shandong Province [ZR2013HM107]	This work was supported by Independent Innovation Foundation of Shandong University (IIFSDU, #2012TS156 for DYL) and Shandong Provincial Natural Science Foundation, China (#ZR2013HM107 for XLP). XLP had a role in the study design. DYL had a role in data analysis.	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J	Fu, L; Han, B; Zhou, Y; Ren, J; Cao, WZ; Patel, G; Kai, GY; Zhang, J				Fu, Li; Han, Bing; Zhou, Yang; Ren, Jie; Cao, Wenzhi; Patel, Gopal; Kai, Guoyin; Zhang, Jun			The Anticancer Properties of Tanshinones and the Pharmacological Effects of Their Active Ingredients	FRONTIERS IN PHARMACOLOGY			English	Review						Salvia miltiorrhiza; tanshinones; autophagy; migration; tumor immunology; apoptosis	COLON-CANCER CELLS; IIA INHIBITS ANGIOGENESIS; MILTIORRHIZA HAIRY ROOTS; IN-VITRO; PROTEIN EXPRESSION; DEPENDENT APOPTOSIS; SIGNALING PATHWAY; HERBAL MEDICINE; DOWN-REGULATION; CYCLE ARREST	Cancer is a common malignant disease worldwide with an increasing mortality in recent years. Salvia miltiorrhiza, a well-known traditional Chinese medicine, has been used for the treatment of cardiovascular and cerebrovascular diseases for thousands of years. The liposoluble tanshinones in S. miltiorrhiza are important bioactive components and mainly include tanshinone IIA, dihydrodanshinone, tanshinone I, and cryptotanshinone. Previous studies showed that these four tanshinones exhibited distinct inhibitory effects on tumor cells through different molecular mechanisms in vitro and in vivo. The mechanisms mainly include the inhibition of tumor cell growth, metastasis, invasion, and angiogenesis, apoptosis induction, cell autophagy, and antitumor immunity, and so on. In this review, we describe the latest progress on the antitumor functions and mechanisms of these four tanshinones to provide a deeper understanding of the efficacy. In addition, the important role of tumor immunology is also reviewed.	[Fu, Li; Zhou, Yang; Ren, Jie; Cao, Wenzhi; Kai, Guoyin; Zhang, Jun] Shanghai Normal Univ, Sch Life Sci, Inst Plant Biotechnol, Shanghai, Peoples R China; [Han, Bing; Patel, Gopal; Kai, Guoyin] Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Lab Med Plant Biotechnol, Hangzhou, Peoples R China		Kai, GY; Zhang, J (corresponding author), Shanghai Normal Univ, Sch Life Sci, Inst Plant Biotechnol, Shanghai, Peoples R China.; Kai, GY (corresponding author), Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Lab Med Plant Biotechnol, Hangzhou, Peoples R China.	guoyinkai@yahoo.com; zhj@shnu.edu.cn	Patel, Gopal/AAH-4185-2020	Patel, Gopal/0000-0001-6193-6847	National Natural Science Fund of ChinaNational Natural Science Foundation of China (NSFC) [81522049, 81670151, 31571735, 31270007]; "Dawn" Program of Shanghai Education Commission [16SG38]; Open project of Shanghai Key Laboratory Atmospheric Particle Pollution Prevention [C-6105-17-029]; Shanghai Science and Technology Committee ProjectShanghai Science & Technology Committee [17JC1404300, 15430502700]; Zhejiang Provincial Ten Thousands Program for Leading Talents of Science and Technology Innovation; Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents; Opening project of Zhejiang provincial preponderant and characteristic subject of Key University (Traditional Chinese Pharmacology); Zhejiang Chinese Medical University [ZYAOXYB2019005, ZYAOX2018019]	This work was supported by the National Natural Science Fund of China (81522049, 81670151, 31571735, and 31270007), the "Dawn" Program of Shanghai Education Commission (16SG38), Open project of Shanghai Key Laboratory Atmospheric Particle Pollution Prevention (C-6105-17-029), Shanghai Science and Technology Committee Project (17JC1404300 and 15430502700), Zhejiang Provincial Ten Thousands Program for Leading Talents of Science and Technology Innovation, Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents, Opening project of Zhejiang provincial preponderant and characteristic subject of Key University (Traditional Chinese Pharmacology), and Zhejiang Chinese Medical University (ZYAOXYB2019005 and ZYAOX2018019).	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Pharmacol.	MAR 19	2020	11								193	10.3389/fphar.2020.00193			18	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	LC8MC	WOS:000525586000001	32265690	Green Published, gold			2022-04-25	
J	Ohashi, Y; Tremel, S; Williams, RL				Ohashi, Yohei; Tremel, Shirley; Williams, Roger L.			VPS34 complexes from a structural perspective	JOURNAL OF LIPID RESEARCH			English	Review						vacuolar protein sorting 34; X-ray crystallography; cryo-electron microscopy; hydrogen-deuterium exchange mass-spectrometry; lipid	PHOSPHATIDYLINOSITOL 3-KINASE COMPLEXES; BECLIN 1; REGULATES AUTOPHAGY; PROTEIN-KINASE; SELECTIVE INHIBITOR; NUTRIENT STRESS; COLON-CANCER; HOPS COMPLEX; UVRAG; GENE	VPS34 phosphorylates phosphatidylinositol to produce PtdIns3P and is the progenitor of the phosphoinositide 3-kinase (PI3K) family. VPS34 has a simpler domain organization than class I PI3Ks, which belies the complexity of its quaternary organization, with the enzyme always functioning within larger assemblies. PtdIns3P recruits specific recognition modules that are common in protein-sorting pathways, such as autophagy and endocytic sorting. It is best characterized in two heterotetramers, complexes I and II. Complex I is composed of VPS34, VPS15, Beclin 1, and autophagy-related gene (ATG)14L, whereas complex II replaces ATG14L with UVRAG. Because VPS34 can form a component of several distinct complexes, it enables independent regulation of various pathways that are controlled by PtdIns3P. Complexes I and II are critical for early events in autophagy and endocytic sorting, respectively. Autophagy has a complex association with cancer. In early stages, it inhibits tumorigenesis, but in later stages, it acts as a survival factor for tumors. Recently, various disease-associated somatic mutations were found in genes encoding complex I and II subunits. Lipid kinase activities of the complexes are also influenced by posttranslational modifications (PTMs). Mapping PTMs and somatic mutations on three-dimensional models of the complexes suggests mechanisms for how these affect VPS34 activity.	[Ohashi, Yohei; Tremel, Shirley; Williams, Roger L.] MRC Lab Mol Biol, Cambridge CB2 0QH, England		Williams, RL (corresponding author), MRC Lab Mol Biol, Cambridge CB2 0QH, England.	rlw@mrc-lmb.cam.ac.uk	Ohashi, Yohei/AAT-4006-2021	Ohashi, Yohei/0000-0002-2288-130X; Tremel, Shirley/0000-0002-4077-0021; Williams, Roger/0000-0001-7754-4207	Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_U105184308]; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MC_U105184308] Funding Source: UKRI	This work was supported by Medical Research Council Grant MC_U105184308.	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Lipid Res.	FEB	2019	60	2					229	241		10.1194/jlr.R089490			13	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	HK8AX	WOS:000458212900003	30397185	Green Published, hybrid			2022-04-25	
J	Yang, LF; Wan, JF; Xiao, S; Barkhouse, D; Zhu, J; Li, GC; Lu, B; Zhang, Z				Yang, Lifeng; Wan, Juefeng; Xiao, Sheng; Barkhouse, Darryll; Zhu, Ji; Li, Guichao; Lu, Bo; Zhang, Zhen			BH3 mimetic ABT-737 sensitizes colorectal cancer cells to ixazomib through MCL-1 downregulation and autophagy inhibition	AMERICAN JOURNAL OF CANCER RESEARCH			English	Article						Colorectal cancer; MLN9708; ABT-737; autophagy; MCL-1	RELAPSED/REFRACTORY MULTIPLE-MYELOMA; ORAL PROTEASOME INHIBITOR; PHASE-II TRIAL; INDUCED APOPTOSIS; ENDOPLASMIC-RETICULUM; TARGETING MCL-1; PROSTATE-CANCER; BCL-2 FAMILY; TUMOR-CELLS; DNA-DAMAGE	The proteasome inhibitor MLN9708 is an orally administered drug that is hydrolyzed into its active form, MLN2238 (ixazomib). Compared with Bortezomib, MLN2238 has a shorter proteasome dissociation half-life and a lower incidence and severity of peripheral neuropathy, which makes it an attractive candidate for colorectal cancer treatment. In the present study, we observed that MLN2238 induced autophagy, as evidenced by conversion of the autophagosomal marker LC3 from LC3I to LC3II, in colorectal cancer cell lines. Mcl-1, an anti-apoptotic Bcl-2 family protein, was markedly elevated after treating a colorectal cancer cell line with MLN2238. We proved that inhibiting Mcl-1 expression enhances MLN2238 induced apoptosis and negatively regulates autophagy. Co-administration of BH3 mimetic ABT-737 with MLN2238 synergistically kills colorectal cancer cells through MCL-1 neutralization and autophagy inhibition. Furthermore, the synergistic killing effect of the combination therapy is correlated with P53 status in colorectal cancer. These data highlight that the combination of ABT-737 with MLN9708 is a promising therapeutic strategy for human colorectal cancer.	[Yang, Lifeng; Wan, Juefeng; Zhu, Ji; Li, Guichao; Zhang, Zhen] Fudan Univ, Shanghai Canc Ctr, Dept Radiat Oncol, Shanghai 200032, Peoples R China; [Yang, Lifeng; Wan, Juefeng; Zhu, Ji; Li, Guichao; Zhang, Zhen] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China; [Xiao, Sheng] Fudan Univ, Shanghai Med Coll, Inst Brain Sci, Dept Integrat Med & Neurobiol,Inst Acupuncture Re, Shanghai 200032, Peoples R China; [Barkhouse, Darryll; Lu, Bo] Thomas Jefferson Univ, Dept Radiat Oncol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA		Lu, B (corresponding author), G 301 Bodine Canc Ctr, 111 S 11th St, Philadelphia, PA 19107 USA.; Zhang, Z (corresponding author), Floor 16,Bldg 3,270 Dongan Rd, Shanghai 200032, Peoples R China.	Bo.Lu@jefferson.edu; zhenzhang6@hot-mail.com		wan, juefeng/0000-0001-5361-1663; Zhu, Ji/0000-0001-7134-9419	Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81372432]	The authors would like to thank Dr. Eric Wickstrom and Dr. Scott Waldman for the cell lines. This work was supported by the grants from Natural Science Foundation of China (81372432). LY, JW participated in manuscript drafting, table creation, and manuscript revision. SX, GL and DB participated the study design and revised the manuscript. JZ revised the manuscript and performed statistical analyses of data. BL and ZZ participated in the study design and were responsible for final approval of the manuscript. All authors have read and approved the final manuscript. The authors declare that they have no conflicts of interests.	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J. Cancer Res.		2016	6	6					1345	+					15	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DQ8GX	WOS:000379448200011	27429848				2022-04-25	
J	Zhang, ZL; Guo, M; Zhao, SF; Xu, WX; Shao, JJ; Zhang, F; Wu, L; Lu, Y; Zheng, SZ				Zhang, Zili; Guo, Mei; Zhao, Shifeng; Xu, Wenxuan; Shao, Jiangjuan; Zhang, Feng; Wu, Li; Lu, Yin; Zheng, Shizhong			The update on transcriptional regulation of autophagy in normal and pathologic cells: A novel therapeutic target	BIOMEDICINE & PHARMACOTHERAPY			English	Review						Autophagy; Transcriptional regulation; Transcription factors; Therapeutic target	NF-KAPPA-B; FARNESOID X RECEPTOR; PPAR-GAMMA ACTIVATION; COLON-CANCER CELLS; POLYCYSTIC-OVARY-SYNDROME; TFEB-MEDIATED AUTOPHAGY; ACUTE LUNG INJURY; UP-REGULATION; IN-VITRO; ENERGY-METABOLISM	Autophagy is a genetically programmed, evolutionarily conserved catabolic process that occurs in response to stress. While short-lived proteins are degraded via the ubiquitin/proteasome pathway in higher eukaryotes, autophagy refers to intracellular pathway for development, differentiation, survival, and homeostasis through the lysosomal-dependent machinery, which regulates the synthesis, degradation, and recycling of long-lived proteins and even whole cytoplasmic organelles. The newly discovery shows that autophagy plays an important role in recycling nutrients upon starvation and maintaining cellular energy homeostasis. Recent basic and clinical investigations further demonstrate that autophagic abnormalities have been considered underlying reasons for lots of human diseases, including liver disease, cardiovascular and cerebrovascular diseases, neurodegenerative diseases, neoplastic diseases, and cancers. Pharmacological modulation of autophagy might point to possible therapeutic strategies for combating a broad range of diseases. Regrettably, although the mechanisms underlying the regulation of autophagy have long been attracted extensive concern of numerous scholars and its acute regulation by nutrient-sensing signaling pathways is well described, the overview on longer-term transcriptional regulation of autophagy is still filled with confusion. This review summarizes current knowledge on transcriptional regulation of autophagy and expands our horizons on the autophagy repertoire. On the other hand, it also offers a glimpse into different strategies that have been used in experimental models to counteract excessive pathological autophagy via transcriptional regulation mechanism in the prevention and treatment of disease. (C) 2015 Elsevier Masson SAS. All rights reserved.	[Zhang, Zili; Zhao, Shifeng; Xu, Wenxuan; Zhang, Feng; Wu, Li; Lu, Yin; Zheng, Shizhong] Nanjing Univ Chinese Med, Dept Pharmacol, Coll Pharm, 138 Xianlin Ave, Nanjing 210023, Jiangsu, Peoples R China; [Guo, Mei] Southeast Univ, Sch Med, Dept Pathogen Biol & Immunol, Nanjing 210009, Peoples R China; [Shao, Jiangjuan] Nanjing Univ Chinese Med, Dept Pharm, Coll Pharm, Nanjing 210023, Jiangsu, Peoples R China; [Zhang, Feng; Wu, Li; Lu, Yin; Zheng, Shizhong] Nanjing Univ Chinese Med, Jiangsu Key Lab Pharmacol & Safety Evaluat Chines, Nanjing 210023, Jiangsu, Peoples R China		Zheng, SZ (corresponding author), Nanjing Univ Chinese Med, Dept Pharmacol, Coll Pharm, 138 Xianlin Ave, Nanjing 210023, Jiangsu, Peoples R China.	nytws@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81270514, 31401210]; Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education; Priority Academic Program Development of Jiangsu Higher Education Institutions [ysxk-2010]; Youth Natural Science Foundation of Jiangsu Province [BK20140955]; Natural Science Research General Program of Jiangsu Higher Education Institutions [14KJB310011]	The nancial support was from the National Natural Science Foundation of China (81270514, 31401210), 2013 Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education, the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (ysxk-2010), the Youth Natural Science Foundation of Jiangsu Province (BK20140955), and the Natural Science Research General Program of Jiangsu Higher Education Institutions (14KJB310011).	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Pharmacother.	AUG	2015	74						17	29		10.1016/j.biopha.2015.06.003			13	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	CR2TD	WOS:000361182600003	26349958				2022-04-25	
J	Zhang, Y; Tian, ZM; Wan, HY; Liu, W; Kong, FP; Ma, GP				Zhang, Yi; Tian, Zhiming; Wan, Hongyan; Liu, Wen; Kong, Fanping; Ma, Guoping			Deltonin Ameliorates Cerebral Ischemia/Reperfusion Injury in Correlation with Modulation of Autophagy and Inflammation	NEUROPSYCHIATRIC DISEASE AND TREATMENT			English	Article						deltonin; cerebral I/R; MCAO/R; autophagy; inflammation	APOPTOSIS; PROTECTS; RATS	Introduction: Deltonin, an active component extracted from Dioscorea zingiberensis C.H. WRIGHT, was widely utilized in traditional Chinese medicines. It has been shown to have anticancer functions such as colon cancer, breast cancer, and head and neck squamous carcinoma. Herein, we will investigate the role of deltonin in cerebral ischemia/reperfusion injuries. Methods: Ly294002 and anisomycin were used as inhibitors to monitor the effects of deltonin. Middle cerebral artery occlusion UR model was constructed. Infarct volumes, neurological deficits and brain water contents were evaluated under different conditions. Rotarod test, ELISA, and Western blotting were carried to investigate the effects in vitro. Results: We found that deltonin in ischemia/reperfusion (UR) rats greatly enhanced brain damages as well as neurological functions through up-regulating p-Akt and p-mTOR as well as inhibiting the expressions of LC3-IULC3-I, Beclin-1, IL-1, TLR4, and p-p38. Deltonin exerted neuroprotection effect through relieving autophagy activity by regulating PI3K/Akt/ mTOR signaling. Deltonin suppressed inflammation reactions through modulation TLR4/ p38/MAPK signaling as well. Conclusion: Overall, our data suggested that deltonin could suppress ischemic brain injury by regulating autophagy and inflammation during I/R. Deltonin can be a potential therapeutic method for patient with I/R.	[Zhang, Yi; Tian, Zhiming; Wan, Hongyan; Liu, Wen] Southeast Univ, Zhongda Hosp, Cerebral Vasc Ctr, Nanjing 210044, Jiangsu, Peoples R China; [Kong, Fanping] Fu Ning Peoples Hosp, Dept Neurol, 111 Bucheng St, Yancheng City 224400, Jiangsu, Peoples R China; [Ma, Guoping] Tian Shui First Peoples Hosp, Dept Neurol, 105 Jianshe Rd, Tianshui City 741000, Gansu, Peoples R China		Kong, FP (corresponding author), Fu Ning Peoples Hosp, Dept Neurol, 111 Bucheng St, Yancheng City 224400, Jiangsu, Peoples R China.; Ma, GP (corresponding author), Tian Shui First Peoples Hosp, Dept Neurol, 105 Jianshe Rd, Tianshui City 741000, Gansu, Peoples R China.	kongfanping_07@163.com; ahygmcynbiis9@163.com					Carloni S, 2008, NEUROBIOL DIS, V32, P329, DOI 10.1016/j.nbd.2008.07.022; Chen A, 2013, MOL MED REP, V8, P1011, DOI 10.3892/mmr.2013.1628; Dai JP, 2018, INT J MOL SCI, V19, DOI 10.3390/ijms19040965; Dawson DA, 1996, J CEREBR BLOOD F MET, V16, P170, DOI 10.1097/00004647-199601000-00020; Gao L, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0046092; Li JS, 2018, INT IMMUNOPHARMACOL, V55, P9, DOI 10.1016/j.intimp.2017.11.040; Li M, 2012, NEUROCHEM INT, V60, P458, DOI 10.1016/j.neuint.2012.01.026; Lin Q, 2010, BRAIN RES, V1325, P183, DOI 10.1016/j.brainres.2010.02.037; Lin Y, 2013, J MOL NEUROSCI, V50, P504, DOI 10.1007/s12031-013-9977-8; Ma S, 2015, BBA-MOL BASIS DIS, V1852, P271, DOI 10.1016/j.bbadis.2014.05.010; Rami A, 2008, NEUROBIOL DIS, V29, P132, DOI 10.1016/j.nbd.2007.08.005; Tong QY, 2011, CELL PHYSIOL BIOCHEM, V27, P233, DOI 10.1159/000327949; Xie YL, 2015, NEOPLASMA, V62, P419, DOI 10.4149/neo_2015_050; Xin XY, 2011, CAN J NEUROL SCI, V38, P631, DOI 10.1017/S031716710001218X; Yasuda N, 2014, BRAIN RES, V1559, P46, DOI 10.1016/j.brainres.2014.02.007; Zausinger S, 2000, BRAIN RES, V863, P94, DOI 10.1016/S0006-8993(00)02100-4; Zhang J, 2014, SCI REP-UK, V4, DOI 10.1038/srep07317; Zhang SY, 2013, MOL MED REP, V7, P1038, DOI 10.3892/mmr.2013.1273; Zhang XN, 2013, AUTOPHAGY, V9, P1321, DOI 10.4161/auto.25132	19	3	6	2	9	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND		1178-2021		NEUROPSYCH DIS TREAT	Neuropsychiatr. Dis. Treat.		2020	16						871	879		10.2147/NDT.S227988			9	Clinical Neurology; Psychiatry	Science Citation Index Expanded (SCI-EXPANDED)	Neurosciences & Neurology; Psychiatry	KY3LV	WOS:000522473700001	32280228	Green Published, gold			2022-04-25	
J	Grosch, S; Schiffmann, S; Geisslinger, G				Groesch, Sabine; Schiffmann, Susanne; Geisslinger, Gerd			Chain length-specific properties of ceramides	PROGRESS IN LIPID RESEARCH			English	Review						Ceramide; Ceramide synthase; Chain length-specific; Apoptosis; Cancer	PROTEIN PHOSPHATASE 2A; LONGEVITY ASSURANCE GENE-1; RADIATION-INDUCED APOPTOSIS; TANDEM MASS-SPECTROMETRY; SQUAMOUS-CELL CARCINOMAS; COLON-CANCER CELLS; KINASE C-ZETA; CYSTIC-FIBROSIS; LONG-CHAIN; SPHINGOLIPID SYNTHESIS	Ceramides are a class of sphingolipids that are abundant in cell membranes. They are important structural components of the membrane but can also act as second messengers in various signaling pathways. Until recently, ceramides and dihydroceramides were considered as a single functional class of lipids and no distinction was made between molecules with different chain lengths. However, based on the development of high-throughput, structure-specific and quantitative analytical methods to measure ceramides, it has now become clear that in cellular systems the amounts of ceramides differ with respect to their chain length. Further studies have indicated that some functions of ceramides are chain-length dependent. In this review, we discuss the chain length-specific differences of ceramides including their pathological impact on Alzheimer's disease, inflammation, autophagy, apoptosis and cancer. (c) 2011 Elsevier Ltd. All rights reserved.	[Groesch, Sabine; Schiffmann, Susanne; Geisslinger, Gerd] Klinikum Johann Wolfgang Goethe Univ Frankfurt, Inst Klin Pharmakol, Pharmazentrum Frankfurt ZAFES, D-60590 Frankfurt, Germany		Grosch, S (corresponding author), Klinikum Johann Wolfgang Goethe Univ Frankfurt, Inst Klin Pharmakol, Pharmazentrum Frankfurt ZAFES, Theodor Stern Kai 7, D-60590 Frankfurt, Germany.	groesch@em.uni-frankfurt.de	Groesch, Sabine/H-4251-2018	Groesch, Sabine/0000-0002-7262-6307; Schiffmann, Susanne/0000-0001-5035-2504	Deutsche Forschungsgemeinschaft (DFG) Forschergruppe FOG 784/TP5German Research Foundation (DFG) [GR2011/2-1]; DFGGerman Research Foundation (DFG)European Commission [GR2011/3-1]; LOEWE Lipid Signaling Forschungszentrum Frankfurt (LiFF)	This work was supported by the Deutsche Forschungsgemeinschaft (DFG) Forschergruppe FOG 784/TP5 (GR2011/2-1) and DFG project GR2011/3-1 and the LOEWE Lipid Signaling Forschungszentrum Frankfurt (LiFF).	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Lipid Res.	JAN	2012	51	1					50	62		10.1016/j.plipres.2011.11.001			13	Biochemistry & Molecular Biology; Nutrition & Dietetics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Nutrition & Dietetics	909JY	WOS:000301562000005	22133871		Y	N	2022-04-25	
J	Aredia, F; Giansanti, V; Mazzini, G; Savio, M; Ortiz, LMG; Jaadane, I; Zaffaroni, N; Forlino, A; Torriglia, A; Scovassi, AI				Aredia, Francesca; Giansanti, Vincenzo; Mazzini, Giuliano; Savio, Monica; Guaman Ortiz, Luis Miguel; Jaadane, Imene; Zaffaroni, Nadia; Forlino, Antonella; Torriglia, Alicia; Scovassi, Anna Ivana			Multiple effects of the Na+/H+ antiporter inhibitor HMA on cancer cells	APOPTOSIS			English	Article						Amiloride; Apoptosis; Autophagy; LEI/L-DNase II; MDR; Parthanatos	MYC AMPLIFICATION LEVEL; DNASE-II; APOPTOSIS; AMILORIDE; THERAPY; PATHWAY; FIBROBLASTS; RESISTANCE; PHENOTYPE; ETOPOSIDE	Amiloride derivatives are a class of new promising chemotherapeutic agents. A representative member of this family is the sodium-hydrogen antiporter inhibitor HMA (5-(N,N-hexamethylene amiloride), which has been demonstrated to induce cellular intracytosolic acidification and cell death through the apoptotic pathway(s). This work aims at characterizing drug response of human cancer cell lines to HMA. After a first screening revealing that HMA interferes with cancer cell survival, we focused our attention on SW613-B3 colon carcinoma cells, which are intrinsically resistant to a panel of drugs. Searching for the activation of canonical apoptosis, we found that this process was abortive, given that the final steps of this process, i.e. PARP-1 cleavage and DNA ladder, were not detectable. Thus, we addressed caspase-independent paradigms of cell death and we observed that HMA promotes the induction of the LEI/L-DNase II pathway as well as of parthanatos. Finally, we explored the possible impact of autophagy of cell response to HMA, providing the evidence that autophagy is activated in our experimental system. On the whole, our results defined the biochemical reactions triggered by HMA, and elucidated its multiple effects, thus adding further complexity to the intricate network leading to drug resistance.	[Aredia, Francesca; Giansanti, Vincenzo; Mazzini, Giuliano; Guaman Ortiz, Luis Miguel; Scovassi, Anna Ivana] CNR, Ist Genet Mol, I-27100 Pavia, Italy; [Savio, Monica] Univ Pavia, Dipartimento Med Mol, Sez Patol Gen, I-27100 Pavia, Italy; [Guaman Ortiz, Luis Miguel] UTPL, Dept Ciencias Salud, Loja 1101608, Ecuador; [Jaadane, Imene; Torriglia, Alicia] INSERM, Ctr Rech Cordeliers, U872, F-75006 Paris, France; [Jaadane, Imene; Torriglia, Alicia] Univ Paris 06, F-75006 Paris, France; [Jaadane, Imene; Torriglia, Alicia] Univ Paris 05, F-75006 Paris, France; [Zaffaroni, Nadia] Fdn IRCCS, Ist Nazl Tumori, I-20133 Milan, Italy; [Forlino, Antonella] Univ Pavia, Dipartimento Biochim, I-27100 Pavia, Italy		Scovassi, AI (corresponding author), CNR, Ist Genet Mol, I-27100 Pavia, Italy.	scovassi@igm.cnr.it	Torriglia, Alicia/L-6957-2017; Torriglia, Alicia/Q-3509-2019; Ortiz, Luis Miguel Guaman/X-9496-2019; Zaffaroni, Nadia/J-8178-2016; Forlino, Antonella/H-5385-2015	Torriglia, Alicia/0000-0003-1181-6710; Ortiz, Luis Miguel Guaman/0000-0003-2919-4905; Zaffaroni, Nadia/0000-0002-4669-0890; Forlino, Antonella/0000-0002-6385-1182; Imene, Jaadane/0000-0003-1887-1659; Scovassi, Anna Ivana/0000-0003-3484-9881	Italian Regione Lombardia; CariploFondazione Cariplo [2011-0270]; SENESCYT (Quito, Ecuador); UTPL (Loja, Ecuador); ADEME	We are indebted to Maria Grazia Bottone for cytoskeleton immunofluorescence, Roberta Gioia for qPCR analysis and Marzia Pennati for survivin experiments. Research was partially granted by Italian Regione Lombardia (Project Plant Cell to A. I. S) and Cariplo (Project 2011-0270 to A. F.). F. A. is a PhD student (Dottorato in Genetica, Biologia Cellulare e Molecolare, University of Pavia, Italy). L.M.G.O. is a PhD student (Dottorato in Genetica, Biologia Cellulare e Molecolare, University of Pavia, Italy) supported by SENESCYT (Quito, Ecuador) and UTPL (Loja, Ecuador). I.J. is supported by an ADEME grant to A.T.	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J	Xiong, B; Chen, S; Zhu, P; Huang, ML; Gao, WJ; Zhu, R; Qian, JQ; Peng, YF; Zhang, YN; Dai, H; Ling, Y				Xiong, Biao; Chen, Shi; Zhu, Peng; Huang, Meiling; Gao, Weijie; Zhu, Rui; Qian, Jianqiang; Peng, Yanfu; Zhang, Yanan; Dai, Hong; Ling, Yong			Design, Synthesis, and Biological Evaluation of Novel Thiazolyl Stibst tilted Bis-pyrazole Oxime Derivatives with Potent Antitumor Activities by Selectively Inducing Apoptosis and ROS in Cancer Cells	MEDICINAL CHEMISTRY			English	Article						Antitumor activities; His-pyrazole oxime derivatives; antiproliferative activity; selectivity; apoptosis; Reactive Oxygen Species (ROS)	ANTICANCER; INDUCTION; AUTOPHAGY	Background: A large number of pyrazole derivatives have different biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic and antiepileptic activity. Among them, pyrazole oximes have attracted much attention due to their potential phannacological activities, particularly anticancer activities. Objective: Our goal is to synthesize novel thiazolyl substituted bis-pyrazole oxime derivatives with potent antitumor activities by selectively inducing apoptosis and Reactive Oxygen Species (ROS) accumulation in cancer cells. Methods: Eighteen his-pyrazole oxirnes were synthesized by conjugating thiazolyl substituted pyrazoles with pyrazoxime. The target compounds were characterized by (HNMR)-H-1, C-13 NMR, and HRMS, and screened for their antiproliferative activity against four cancer cells in MTT assay. The most potent compound was examined for its inhibitory effect and ROS accumulation in both cancer cells HCT116 and normal intestinal epithelial cells CCD841. Finally, the most potent compound was further evaluated for its apoptotic induction by flow cytometry analysis and immunoblot analysis of apoptosis-related proteins and DNA damage proteins. Results: Most compounds displayed potent antiproliferative activity against four cancer cell lines in vitro, displaying potencies superior to 5-FU. In particular, the most potent compound 131 selectively inhibited proliferation of colorectal cancer HCT116 cells but not normal colon CCD841 cells. Furthermore, compound 131 also selectively promoted intracellular ROS accumulation in HCT I 16 which was involved in 131 inhibition of cancer cell proliferation and induction of cell alxmptosis. Finally, compound 131 also dose-dependently induced cancer cell apoptosis by regulating apoptotic and DNA damage related proteins expressions, Conclusion: Our synthetic his-pyrazole oxime derivatives possess potent antitumor activities by selectively inducing apoptosis and ROS accumulation in cancer cells, Which may hold great promise as therapeutic agents for the treatment of human cancers.	[Xiong, Biao; Chen, Shi; Zhu, Peng; Huang, Meiling; Gao, Weijie; Zhu, Rui; Qian, Jianqiang; Peng, Yanfu; Zhang, Yanan; Dai, Hong; Ling, Yong] Nantong Univ, Sch Pharm, Nantong 226001, Peoples R China; [Xiong, Biao; Chen, Shi; Zhu, Peng; Huang, Meiling; Gao, Weijie; Zhu, Rui; Qian, Jianqiang; Peng, Yanfu; Zhang, Yanan; Dai, Hong; Ling, Yong] Nantong Univ, Jiangsu Prov Key Lab Inflammat & Mol Drug Target, Nantong 226001, Peoples R China; [Huang, Meiling; Dai, Hong; Ling, Yong] Nantong Univ, Coll Chem & Chem Engn, Nantong 226001, Peoples R China; [Ling, Yong] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China		Dai, H; Ling, Y (corresponding author), Nantong Univ, Sch Pharm, Nantong 226001, Peoples R China.; Dai, H; Ling, Y (corresponding author), Nantong Univ, Jiangsu Prov Key Lab Inflammat & Mol Drug Target, Nantong 226001, Peoples R China.; Dai, H; Ling, Y (corresponding author), Nantong Univ, Coll Chem & Chem Engn, Nantong 226001, Peoples R China.; Ling, Y (corresponding author), China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China.	dh123@ntu.edu.cn; lyyy111@sina.com		zhu, peng/0000-0002-4148-9135	Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81302628, 21372135]; Project of "Jiangsu Six Peaks of Talent", China [2013-SWYY-013, 2014-SWYY-044, 2016-SWYYCXTD-008]; Jiangsu Province Postdoctoral Science Foundation [2018T110533, 2016M590488, 1601136B]; Applied Research Projects of Nantong City [MS12018079, JC2018125]; Priority Academic Programs Development of Jiangsu Higher Education Institutions (PAPD); Project of "Jiangsu 333 high-level talents"	We gratefully acknowledge the financial support by the Natural Science Foundation of China (Grant Nos. 81302628 and 21372135), the Project of "Jiangsu Six Peaks of Talent" (2013-SWYY-013, 2014-SWYY-044, and 2016-SWYYCXTD-008), China and Jiangsu Province Postdoctoral Science Foundation (2018T110533, 2016M590488, and 1601136B), the Project of "Jiangsu 333 high-level talents", Applied Research Projects of Nantong City (MS12018079 and JC2018125), and also thank a project funded by the Priority Academic Programs Development of Jiangsu Higher Education Institutions (PAPD).	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Chem.		2019	15	7					743	754		10.2174/1573406414666180827112724			12	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	JD4QE	WOS:000489963500004	30147012				2022-04-25	
J	Ahmed, S; Khan, H; Aschner, M; Mirzae, H; Akkol, EK; Capasso, R				Ahmed, Salman; Khan, Haroon; Aschner, Michael; Mirzae, Hamed; Akkol, Esra Kupeli; Capasso, Raffaele			Anticancer Potential of Furanocoumarins: Mechanistic and Therapeutic Aspects	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						furanocoumarin; apoptosis; autophagy; metastasis; cell cycle arrest	NF-KAPPA-B; MEDIATED MULTIDRUG-RESISTANCE; CELL-CYCLE ARREST; IN-VITRO; ANGELICA-DAHURICA; CANCER-CELLS; MATRIX METALLOPROTEINASES; DIETARY FUROCOUMARINS; SIGNALING PATHWAY; PSORALEN REVERSES	Cancer is one of the most extreme medical conditions in both developing and developed countries around the world, causing millions of deaths each year. Chemotherapy and/or radiotherapy are key for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer overall requires novel efficacious treatment modalities. Natural medications offer feasible alternative options against malignancy in contrast to western medication. Furanocoumarins' defensive and restorative impacts have been observed in leukemia, glioma, breast, lung, renal, liver, colon, cervical, ovarian, and prostate malignancies. Experimental findings have shown that furanocoumarins activate multiple signaling pathways, leading to apoptosis, autophagy, antioxidant, antimetastatic, and cell cycle arrest in malignant cells. Additionally, furanocoumarins have been shown to have chemo preventive and chemotherapeutic synergistic potential when used in combination with other anticancer drugs. Here, we address different pathways which are activated by furanocoumarins and their therapeutic efficacy in various tumors. Ideally, this review will trigger interest in furanocoumarins and their potential efficacy and safety as a cancer lessening agents.	[Ahmed, Salman] Univ Karachi, Fac Pharm & Pharmaceut Sci, Dept Pharmacognosy, Karachi 75270, Pakistan; [Khan, Haroon] Abdul Wali Khan Univ, Dept Pharm, Mardan 23200, Pakistan; [Aschner, Michael] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10463 USA; [Mirzae, Hamed] Kashan Univ Med Sci, Res Ctr Biochem & Nutr Metab Dis, Inst Basic Sci, Kashan 8715973474, Iran; [Akkol, Esra Kupeli] Gazi Univ, Fac Pharm, Dept Pharmacognosy, TR-06330 Ankara, Turkey; [Capasso, Raffaele] Univ Naples Federico II, Dept Agr Sci, Via Univ 100, I-80055 Portici, Italy		Capasso, R (corresponding author), Univ Naples Federico II, Dept Agr Sci, Via Univ 100, I-80055 Portici, Italy.	salmanahmed@uok.edu.pk; haroonkhan@awkum.edu.pk; michael.aschner@einsteinmed.org; mirzaeih911h@mums.ac.ir; esrak@gazi.edu.tr; rafcapas@unina.it	Akkol, Esra/ABI-4678-2020; Ahmed, Salman/B-8789-2015; Khan, Haroon/AAY-1785-2020	Ahmed, Salman/0000-0003-2033-0181; Khan, Haroon/0000-0002-1736-4404; Capasso, Raffaele/0000-0002-3335-1822; Kupeli Akkol, Esra/0000-0002-5829-7869			Acharya R, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-52162-0; Ahmed S, 2019, PHYTOMEDICINE, V59, DOI 10.1016/j.phymed.2019.152883; Alzahrani AM, 2020, OXID MED CELL LONGEV, V2020, DOI 10.1155/2020/3028387; Am J.U., 2018, J BUON, V22, P1471; Del Rio JA, 2014, STUD NAT PROD CHEM, V43, P145, DOI 10.1016/B978-0-444-63430-6.00005-9; Aoki Y, 2003, BLOOD, V101, P1535, DOI 10.1182/blood-2002-07-2130; Artacho-Cordon F, 2012, SURG ONCOL, V21, pE143, DOI 10.1016/j.suronc.2012.06.001; Ashraf MA, 2020, BIOMED RES INT, V2020, DOI 10.1155/2020/8602879; Augustin S, 2009, ANTICANCER RES, V29, P1335; Bartnik M, 2017, J ETHNOPHARMACOL, V207, P19, DOI 10.1016/j.jep.2017.06.010; Bor G, 2019, THER DELIV, V10, P113, DOI 10.4155/tde-2018-0062; Brigger I, 2002, ADV DRUG DELIVER REV, V54, P631, DOI 10.1016/S0169-409X(02)00044-3; Burroughs SK, 2013, FUTURE MED CHEM, V5, P553, DOI [10.4155/FMC.13.17, 10.4155/fmc.13.17]; Cao YJ, 2014, J AM SOC HYPERTENS, V8, P527, DOI 10.1016/j.jash.2014.04.006; Carbone A, 2019, EUR J MED CHEM, V180, P283, DOI 10.1016/j.ejmech.2019.07.025; Chase AJ, 2002, ARTERIOSCL THROM VAS, V22, P765, DOI 10.1161/01.ATV.0000015078.09208.92; Chen N, 2011, CANCER BIOL THER, V11, P157, DOI 10.4161/cbt.11.2.14622; Cheng X, 2018, CURR TOP MED CHEM, V18, P484, DOI 10.2174/1568026618666180523104541; Chiang SR, 2019, MOL MED REP, V19, P1972, DOI 10.3892/mmr.2019.9810; Choochuay K, 2013, J NAT MED-TOKYO, V67, P599, DOI 10.1007/s11418-012-0719-y; De Amicis F, 2015, MOL CANCER, V14, DOI 10.1186/s12943-015-0403-4; DelRosso G., 2017, ADV CLIN PRACT, V137, P151, DOI [10.5772/65712, DOI 10.5772/65712]; Deng Lei, 2002, Cancer Treat Res, V112, P49; Dewanjee S, 2017, MOLECULES, V22, DOI 10.3390/molecules22060871; Dhalwal K, 2008, PHARM BIOL, V46, P266, DOI 10.1080/13880200701741088; Dong L, 2018, ONCOL REP, V39, P597, DOI 10.3892/or.2017.6147; Dowdy JC, 2016, J CLIN ONCOL, V34, P636, DOI 10.1200/JCO.2015.63.8643; Elmore S, 2007, TOXICOL PATHOL, V35, P495, DOI 10.1080/01926230701320337; Embade N, 2000, MOL BIOL CELL, V11, P4347, DOI 10.1091/mbc.11.12.4347; Escarcega RO, 2007, CLIN ONCOL-UK, V19, P154, DOI 10.1016/j.clon.2006.11.013; Fang H, 2019, ANTI-CANCER AGENT ME, V19, P2091, DOI 10.2174/1871520619666191010102526; Faraone I, 2020, PHARMACOL RES, V155, DOI 10.1016/j.phrs.2020.104689; Fletcher JI, 2010, NAT REV CANCER, V10, P147, DOI 10.1038/nrc2789; Fujioka T, 1999, CHEM PHARM BULL, V47, P96, DOI 10.1248/cpb.47.96; Gastonguay AJ, 2012, CANCER BIOL THER, V13, P647, DOI 10.4161/cbt.20082; GAWRON A, 1987, PLANTA MED, V53, P526, DOI 10.1055/s-2006-962801; Ge ZC, 2016, BANGL J PHARMACOL, V11, P489, DOI 10.3329/bjp.v11i2.24644; Godwin P, 2013, FRONT ONCOL, V3, DOI 10.3389/fonc.2013.00120; Guillon CD, 2019, BIOORG MED CHEM LETT, V29, P619, DOI 10.1016/j.bmcl.2018.12.048; Haq SH, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-55309-1; Harris SL, 2005, ONCOGENE, V24, P2899, DOI 10.1038/sj.onc.1208615; Haseeb M, 2019, CELLS-BASEL, V8, DOI 10.3390/cells8111380; Hasitha P, 2018, BIOMED PHARMACOTHER, V106, P98, DOI 10.1016/j.biopha.2018.06.053; He K, 2003, U.S. Patent No, Patent No. [6,509,371B1, 6509371]; Herynk MH, 2007, ADV EXP MED BIOL, V608, P130; Hsieh MJ, 2014, PHYTOMEDICINE, V21, P970, DOI 10.1016/j.phymed.2014.03.008; Hu JJ, 2016, TUMOR BIOL, V37, P331, DOI 10.1007/s13277-015-3591-z; Huang QQ, 2018, DRUG DELIV, V25, P1056, DOI 10.1080/10717544.2018.1464084; Hung WL, 2017, J FOOD DRUG ANAL, V25, P71, DOI 10.1016/j.jfda.2016.11.008; Hwang YP, 2010, MOL NUTR FOOD RES, V54, P977, DOI 10.1002/mnfr.200900283; Ingham M, 2017, J CLIN ONCOL, V35, P2949, DOI 10.1200/JCO.2016.69.0032; Jakubowicz-Gil J, 2012, FOLIA HISTOCHEM CYTO, V50, P381, DOI [10.5603/FHC.2012.0052, 10.5603/19747]; Jiang JR, 2016, MOL MED REP, V13, P4745, DOI 10.3892/mmr.2016.5098; Kaewpiboon C, 2014, INT J ONCOL, V44, P1233, DOI 10.3892/ijo.2014.2297; Kang J. 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J. Mol. Sci.	AUG	2020	21	16							5622	10.3390/ijms21165622			20	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	NI1OD	WOS:000565126300001	32781533	Green Published, gold			2022-04-25	
J	Emama, AA; Abo-Elkhair, SM; Sobh, M; El-Sokkary, AMA				Emama, Ahmed A.; Abo-Elkhair, Salwa M.; Sobh, Mohamed; El-Sokkary, Ahmed M. A.			Role of exopolysaccharides (EPSs) as anti-Mir-155 in cancer cells	HELIYON			English	Article						Exopolysaccharides; miR-155; Cancer cell lines; HCC; Breast cancer; Colon cancer	TUMOR-SUPPRESSOR; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; BETA-CATENIN; EXPRESSION; MICRORNA-155; APOPTOSIS; AUTOPHAGY; ONCOMIR	Micro-RNAs (MiRNAs) are a class of small non-coding RNAs that regulate cellular gene expression. MiR-155 overexpression has been implicated in many types of cancer. Besides, miR-155 appears to help tumor invasion and migration and works as a moderator of epithelial-to-mesenchymal transition (EMT). Exopolysaccharides (EPSs) are a large group of natural heterogeneous polymers of sugars with a biologically antitumor effect. Herein, we test a hypothesis that EPS might promote its anti-tumorigenic effect via regulating miR-155 expression and its target pathways. Expression of miR-155 and a panel of targeted genes were investigated by real-time PCR. In our study, we have succeeded in the extraction, purification of exopolysaccharide with great cytotoxicity to different cancer cell lines, HepG II, Caco-2, and MCF-7. We reported that EPSs have a suppression effect on the oncogenic miR-155. In conclusion, this work clarifies a new possible mechanism for the anti-tumorigenic effect of EPSs in cancer cells and provides insights into the biological pathways through which EPSs act. Moreover, it paves the way for new prospective cancer therapeutics as anti-miRNA.	[Emama, Ahmed A.; Sobh, Mohamed] Mansoura Univ, Fac Med, Med Expt Res Ctr MERC, Mansoura, Egypt; [Abo-Elkhair, Salwa M.] Mansoura Univ, Fac Med, Med Biochem & Mol Biol Dept, Mansoura, Egypt; [Sobh, Mohamed] Mansoura Univ, Urol & Nephrol Ctr, Fac Med, Mansoura, Egypt; [El-Sokkary, Ahmed M. A.] Mansoura Univ, Fac Sci, Chem Dept, Biochem Div, Mansoura, Egypt		El-Sokkary, AMA (corresponding author), Mansoura Univ, Fac Sci, Chem Dept, Biochem Div, Mansoura, Egypt.	aelsokkary@mans.edu.eg		Emam, Ahmed Abdou/0000-0002-4391-9725			Abd El Ghany K, 2015, BIOTECHNOL BIOTEC EQ, V29, P977, DOI 10.1080/13102818.2015.1050455; Al-Suhaibani E.S., 2015, INT J SCI RES, V4, P2283; Alajez NM, 2016, SAUDI J GASTROENTERO, V22, P288, DOI 10.4103/1319-3767.187602; Beaurivage C, 2016, CYTOKINE, V82, P87, DOI 10.1016/j.cyto.2016.01.005; Chang SH, 2011, NAT MED, V17, P1275, DOI 10.1038/nm.2459; Cheng CJ, 2015, NATURE, V518, P107, DOI 10.1038/nature13905; Di W, 2018, ONCOL LETT, V16, P3577, DOI 10.3892/ol.2018.9129; El-Deeb NM, 2018, MICROB CELL FACT, V17, DOI 10.1186/s12934-018-0877-z; Guan CN, 2016, ONCOL LETT, V11, P1574, DOI 10.3892/ol.2015.4048; Han PP, 2014, APPL BIOCHEM BIOTECH, V172, P36, DOI 10.1007/s12010-013-0505-7; Ji JF, 2015, HEPATOLOGY, V62, P829, DOI 10.1002/hep.27886; Jiang SA, 2010, CANCER RES, V70, P3119, DOI 10.1158/0008-5472.CAN-09-4250; Kawahigashi Yutaka, 2009, Journal of Nippon Medical School, V76, P188; Li W, 2015, CARBOHYD RES, V411, P6, DOI 10.1016/j.carres.2014.12.014; Lin SY, 2000, P NATL ACAD SCI USA, V97, P4262, DOI 10.1073/pnas.060025397; Liu CY, 2016, ONCOL LETT, V12, P5177, DOI 10.3892/ol.2016.5326; Mahgoub A.M., 1957, ASIAN PAC J CANC PRE, V19; Mao BJ, 2015, ONCOL REP, V34, P2811, DOI 10.3892/or.2015.4275; Meng FY, 2007, GASTROENTEROLOGY, V133, P647, DOI 10.1053/j.gastro.2007.05.022; Mojibi Parisa, 2019, Iran J Pathol, V14, P41, DOI 10.30699/IJP.14.1.41; Morishita A, 2015, HEPATOL RES, V45, P128, DOI 10.1111/hepr.12386; Nami Y, 2015, FRONT MICROBIOL, V6, DOI 10.3389/fmicb.2015.01317; Oh Jung Young, 2008, J Microbiol Biotechnol, V18, P512; Qi QM, 2018, ONCOL LETT, V15, P6400, DOI 10.3892/ol.2018.8177; Shibuya H, 2010, ONCOLOGY-BASEL, V79, P313, DOI 10.1159/000323283; Singh R, 2013, CANCER BIOL THER, V14, P201, DOI 10.4161/cbt.23296; Sivridis E, 2010, AM J PATHOL, V176, P2477, DOI 10.2353/ajpath.2010.090049; Sun NX, 2018, MOLECULES, V23, DOI 10.3390/molecules23112898; Svoronos AA, 2016, CANCER RES, V76, P3666, DOI 10.1158/0008-5472.CAN-16-0359; Takashina M, 2017, INT J ONCOL, V50, P787, DOI 10.3892/ijo.2017.3859; Tao J.Y., 2018, LIVER RES, V2, P61, DOI DOI 10.1016/J.LIVRES.2018.06.002; Valeri N, 2010, P NATL ACAD SCI USA, V107, P6982, DOI 10.1073/pnas.1002472107; Venkatadri R, 2016, CELL DEATH DIS, V7, DOI 10.1038/cddis.2016.6; Vidhyalakshmi R., 2013, J CANC SCI THER, V5, P31; Wan G, 2014, AUTOPHAGY, V10, P70, DOI 10.4161/auto.26534; Wang GD, 2016, CARBOHYD POLYM, V136, P1065, DOI 10.1016/j.carbpol.2015.09.108; Yang NN, 2015, ADV DRUG DELIVER REV, V81, P62, DOI 10.1016/j.addr.2014.10.029; Yoshida N, 2015, ANTICANCER RES, V35, P4403; Zadeh MM, 2016, J BREAST CANCER, V19, P45, DOI 10.4048/jbc.2016.19.1.45	39	0	0	0	2	ELSEVIER SCI LTD	OXFORD	THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND		2405-8440		HELIYON	Heliyon	APR	2021	7	4							e06698	10.1016/j.heliyon.2021.e06698		APR 2021	9	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	UW4KX	WOS:000700128000018	33869874	gold, Green Published			2022-04-25	
J	Chen, MB; Liu, YY; Xing, ZY; Zhang, ZQ; Jiang, Q; Lu, PH; Cao, C				Chen, Min-Bin; Liu, Yuan-Yuan; Xing, Zhao-Yu; Zhang, Zhi-Qing; Jiang, Qin; Lu, Pei-Hua; Cao, Cong			Itraconazole-Induced Inhibition on Human Esophageal Cancer Cell Growth Requires AMPK Activation	MOLECULAR CANCER THERAPEUTICS			English	Article							PROTEIN-KINASE; COLORECTAL-CANCER; LIVER-CELLS; PATHWAY; PHOSPHORYLATION; METABOLISM; APOPTOSIS; MTOR; AUTOPHAGY; ULK1	We here evaluated the antiesophageal cancer cell activity by the antifungal drug itraconazole. Our results show that mg/mL concentrations of itraconazole potently inhibited survival and proliferation of established (TE-1 and Eca-109) and primary human esophageal cancer cells. Itraconazole activated AMPK signaling, which was required for subsequent esophageal cancer cell death. Pharmacologic AMPK inhibition, AMPKa1 shRNA, or dominant negative mutation (T172A) almost completely abolished itraconazole-induced cytotoxicity against esophageal cancer cells. Significantly, itraconazole induced AMPK-dependent autophagic cell death (but not apoptosis) in esophageal cancer cells. Furthermore, AMPK activation by itraconazole induced multiple receptor tyrosine kinases (RTKs: EGFR, PDGFRa, and PDGFRb), lysosomal translocation, and degradation to inhibit downstream Akt activation. In vivo, itraconazole oral gavage potently inhibited Eca-109 tumor growth in SCID mice. It was yet ineffective against AMPKa1 shRNA-expressing Eca-109 tumors. The in vivo growth of the primary human esophageal cancer cells was also significantly inhibited by itraconazole administration. AMPK activation, RTK degradation, and Akt inhibition were observed in itraconazole-treated tumors. Together, itraconazole inhibits esophageal cancer cell growth via activating AMPK signaling. (C) 2018 AACR.	[Chen, Min-Bin] Jiangsu Univ, Kunshan Peoples Hosp 1, Dept Radiotherapy & Oncol, Kunshan, Peoples R China; [Liu, Yuan-Yuan] Jiangsu Univ, Kunshan Peoples Hosp 1, Clin Res & Lab Ctr, Kunshan, Peoples R China; [Xing, Zhao-Yu] Soochow Univ, Affiliated Hosp 3, Dept Urol, Changzhou, Peoples R China; [Zhang, Zhi-Qing; Cao, Cong] Soochow Univ, Inst Neurosci, Suzhou, Peoples R China; [Jiang, Qin; Cao, Cong] Nanjing Med Univ, Affiliated Eye Hosp, Nanjing, Jiangsu, Peoples R China; [Lu, Pei-Hua] Nanjing Med Univ, Wuxi Peoples Hosp, Dept Med Oncol, 299 Qingyang Rd, Wuxi 214023, Peoples R China; [Cao, Cong] Municipal Hosp Suzhou, Suzhou, Peoples R China		Lu, PH (corresponding author), Nanjing Med Univ, Wuxi Peoples Hosp, Dept Med Oncol, 299 Qingyang Rd, Wuxi 214023, Peoples R China.; Jiang, Q (corresponding author), Nanjing Med Univ, Affiliated Eye Hosp, 138 Han Zhong Rd, Nanjing 210029, Jiangsu, Peoples R China.; Cao, C (corresponding author), Soochow Univ, SIP, 199 Renai Rd, Suzhou 215123, Jiangsu, Peoples R China.	Jqin710@vip.sina.com; lphty1_1@163.com; caocong@suda.edu.cn		Lu, Peihua/0000-0002-4622-3061; , Min-Bin/0000-0003-1453-8664	National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81771457/81302195/31371139/81571282, 81472786/81773192, 81502162, 81472305]; Six Talents Peak Project of Jiangsu Province [2014-WSN-012, 2014-WSN-061]; Kunshan Science and Technology Program [KS1418]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20130301/BK20170060, BK20171248]	This work is supported by the National Natural Science Foundation (81771457/81302195/31371139/81571282 to C. Cao, 81472786/81773192 to M. B. Chen, 81472305 to P. H. Lu, and 81502162 to Z. Q. Zhang), the Six Talents Peak Project of Jiangsu Province (2014-WSN-012 to M. B. Chen and 2014-WSN-061 to P. H. Lu), Kunshan Science and Technology Program (KS1418 to M. B. Chen), and by grants from Natural Science Foundation of Jiangsu Province (BK20130301/BK20170060 to C. Cao and BK20171248 to M. B. Chen).	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Cancer Ther.	JUN	2018	17	6					1229	1239		10.1158/1535-7163.MCT-17-1094			11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GH8QG	WOS:000433932800009	29592879	Bronze			2022-04-25	
J	Panganiban, RAM; Snow, AL; Day, RM				Panganiban, Ronald-Allan M.; Snow, Andrew L.; Day, Regina M.			Mechanisms of Radiation Toxicity in Transformed and Non-Transformed Cells	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						ionizing radiation; apoptosis; necrosis; senescence; autophagy; cancer; primary cell	ENDOPLASMIC-RETICULUM STRESS; RAT LUNG IRRADIATION; DOUBLE-STRAND BREAKS; CASPASE RECRUITMENT DOMAIN; COLON-CANCER CELLS; FACTOR-KAPPA-B; WILD-TYPE P53; IONIZING-RADIATION; INDUCED APOPTOSIS; CELLULAR SENESCENCE	Radiation damage to biological systems is determined by the type of radiation, the total dosage of exposure, the dose rate, and the region of the body exposed. Three modes of cell deathnecrosis, apoptosis, and autophagyas well as accelerated senescence have been demonstrated to occur in vitro and in vivo in response to radiation in cancer cells as well as in normal cells. The basis for cellular selection for each mode depends on various factors including the specific cell type involved, the dose of radiation absorbed by the cell, and whether it is proliferating and/or transformed. Here we review the signaling mechanisms activated by radiation for the induction of toxicity in transformed and normal cells. Understanding the molecular mechanisms of radiation toxicity is critical for the development of radiation countermeasures as well as for the improvement of clinical radiation in cancer treatment.	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J. Mol. Sci.	AUG	2013	14	8					15931	15958		10.3390/ijms140815931			28	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	272ZE	WOS:000328501300039	23912235	gold, Green Submitted, Green Published			2022-04-25	
J	Kandouz, M				Kandouz, Mustapha			Dying to communicate: apoptotic functions of Eph/Ephrin proteins	APOPTOSIS			English	Review						Eph receptor; Ephrin; Cell-cell communication; Intercellular communication; Apoptosis	RECEPTOR TYROSINE KINASE; AUTOPHAGIC CELL-DEATH; SPINAL-CORD-INJURY; COLORECTAL-CANCER PROGRESSION; TRAUMATIC BRAIN-INJURY; RETINAL GANGLION-CELLS; MAMMARY-GLAND DEVELOPMENT; LIPID-BINDING PROTEIN; EPH RECEPTORS; TUMOR-GROWTH	The Erythropoietin-producing human hepatocellular carcinoma (Eph) receptors constitute the largest family of receptor tyrosine kinases and interact with a group of ligands called Ephrins. An essential feature of the Eph receptors and Ephrin ligands is that both are membrane-bound and, upon cell-cell interaction, initiate a bidirectional signaling involving both the receptor (forward signaling) and the ligand (reverse signaling). They regulate a large set of pleiotropic functions in virtually every tissue and physiological system. In vitro as well as in vivo data support a role for Eph and Ephrin molecules in cellular processes such as proliferation, cell-cell attraction and repulsion, motility and sorting. An increasing amount of evidence supports a role for these molecules in apoptosis and, although this function in cell death has been barely examined, the available information warrants a global consideration, to identify unmet needs and potential research avenues. Here we propose a comprehensive analysis of the data available regarding the importance of Ephs and Ephrins in cell death mechanisms throughout a large array of physiological systems.	[Kandouz, Mustapha] Wayne State Univ, Sch Med, Dept Pathol, Scott Hall Bldg Room 9207,540 East Canfield, Detroit, MI 48201 USA; [Kandouz, Mustapha] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA		Kandouz, M (corresponding author), Wayne State Univ, Sch Med, Dept Pathol, Scott Hall Bldg Room 9207,540 East Canfield, Detroit, MI 48201 USA.; Kandouz, M (corresponding author), Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.	ag1764@wayne.edu					Akada M, 2014, CELL SIGNAL, V26, P2879, DOI 10.1016/j.cellsig.2014.08.031; Alfaro D, 2008, IMMUNOLOGY, V125, P131, DOI 10.1111/j.1365-2567.2008.02828.x; Alfaro D, 2007, EUR J IMMUNOL, V37, P2596, DOI 10.1002/eji.200737097; Alfaro D, 2011, IMMUNOL CELL BIOL, V89, P844, DOI 10.1038/icb.2010.172; Allan EH, 2008, J BONE MINER RES, V23, P1170, DOI 10.1359/JBMR.080324; Amaravadi RK, 2011, CLIN CANCER RES, V17, P654, DOI 10.1158/1078-0432.CCR-10-2634; ANDRES AC, 1994, ONCOGENE, V9, P1461; Arakaki R, 2014, CRIT REV IMMUNOL, V34, P301, DOI 10.1615/CritRevImmunol.2014009988; 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Cell Biology	GJ2SP	WOS:000435123200003	29767378				2022-04-25	
J	Yang, PM; Lin, YT; Shun, CT; Lin, SH; Wei, TT; Chuang, SH; Wu, MS; Chen, CC				Yang, Pei-Ming; Lin, Yi-Ting; Shun, Chia-Tung; Lin, Shan-Hu; Wei, Tzu-Tang; Chuang, Shu-Hui; Wu, Ming-Shiang; Chen, Ching-Chow			Zebularine inhibits tumorigenesis and stemness of colorectal cancer via p53-dependent endoplasmic reticulum stress	SCIENTIFIC REPORTS			English	Article							UNFOLDED PROTEIN RESPONSE; ACUTE MYELOID-LEUKEMIA; CYTIDINE DEAMINASE; CELL-DEATH; CARCINOMA-CELLS; DNA METHYLATION; AUTOPHAGY; P53; 5-AZACYTIDINE; GENE	Aberrant DNA hypermethylation is frequently found in tumor cells and inhibition of DNA methylation is an effective anticancer strategy. In this study, the therapeutic effect of DNA methyltransferase (DNMT) inhibitor zebularine (Zeb) on colorectal cancer (CRC) was investigated. Zeb exhibited anticancer activity in cell cultures, tumor xenografts and mouse colitis-associated CRC model. It stabilizes p53 through ribosomal protein S7 (RPS7)/MDM2 pathways and DNA damage. Zeb-induced cell death was dependent on p53. Microarray analysis revealed that genes related to endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were affected by Zeb. Zeb induced p53-dependent ER stress and autophagy. Pro-survival markers of ER stress/UPR (GRP78) and autophagy (p62) were increased in tumor tissues of CRC patients, AOM/DSS-induced CRC mice and HCT116-derived colonospheres. Zeb downregulates GRP78 and p62, and upregulates a pro-apoptotic CHOP. Our results reveal a novel mechanism for the anticancer activity of Zeb.	[Yang, Pei-Ming; Lin, Yi-Ting; Lin, Shan-Hu; Wei, Tzu-Tang; Chuang, Shu-Hui; Chen, Ching-Chow] Natl Taiwan Univ, Coll Med, Dept Pharmacol, Taipei 10764, Taiwan; [Yang, Pei-Ming] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Biol & Drug Discovery, Taipei, Taiwan; [Shun, Chia-Tung] Natl Taiwan Univ Hosp, Dept Forens Med & Pathol, Taipei, Taiwan; [Wu, Ming-Shiang] Natl Taiwan Univ Hosp, Dept Internal Med, Div Gastroenterol, Taipei 100, Taiwan		Chen, CC (corresponding author), Natl Taiwan Univ, Coll Med, Dept Pharmacol, Taipei 10764, Taiwan.	chingchowchen@ntu.edu.tw	Shun, Chia-Tung/M-1400-2019; Yang, Pei-Ming/G-3763-2014; WEI, TZU-TANG/AAT-8447-2020; CHUANG, SHU-HUI/F-8625-2017	Yang, Pei-Ming/0000-0002-4004-2518; Wu, Ming-Shiang/0000-0002-1940-6428; CHEN, CHING-CHOW/0000-0002-7810-0939; SHUN, CHIA-TUNG/0000-0002-0468-4468; CHUANG, SHU-HUI/0000-0002-6123-3874	National Science Council of TaiwanMinistry of Science and Technology, Taiwan	This work was supported by a research grant from the National Science Council of Taiwan.	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J	Hu, JL; He, GY; Lan, XL; Zeng, ZC; Guan, J; Ding, Y; Qian, XL; Liao, WT; Ding, YQ; Liang, L				Hu, J. L.; He, G. Y.; Lan, X. L.; Zeng, Z. C.; Guan, J.; Ding, Y.; Qian, X. L.; Liao, W. T.; Ding, Y. Q.; Liang, L.			Inhibition of ATG12-mediated autophagy by miR-214 enhances radiosensitivity in colorectal cancer	ONCOGENESIS			English	Article							HYPOXIA-INDUCED AUTOPHAGY; DOWN-REGULATION; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; NASOPHARYNGEAL CARCINOMA; LUNG-CANCER; CELLS; RADIATION; APOPTOSIS; RADIORESISTANCE	Radioresistance hampers success in the treatment of patients with advanced colorectal cancer (CRC). Improving our understanding of the underlying mechanisms of radioresistance could increase patients' response to irradiation (IR). MicroRNAs are a class of small RNAs involved in tumor therapy response to radiation. Here we found that miR-214 was markedly decreased in CRC cell lines and blood of CRC patients after IR exposure. Meanwhile, autophagy was enhanced in irradiated CRC cells. Mechanically, ATG12 was predicted and identified as a direct target of miR-214 by dual luciferase assay, qPCR, and Western blot. In vitro and in vivo experiments showed that miR-214 promoted radiosensitivity by inhibiting IR-induced autophagy. Restoration of ATG12 attenuated miR-214-mediated inhibition of cell growth and survival in response to IR. Importantly, miR-214 was highly expressed in radiosensitive CRC specimens and negatively correlated with plasma level of CEA. Moreover, ATG12 and LC3 expressions were increased in radioresistant CRC specimens. Our study elucidates that miR-214 promotes radiosensitivity by inhibition of ATG12-mediated autophagy in CRC. Importantly, miR-214 is a determinant of CRC irradiation response and may serve as a potential therapeutic target in CRC treatment.	[Hu, J. L.; He, G. Y.; Lan, X. L.; Zeng, Z. C.; Liao, W. T.; Ding, Y. Q.; Liang, L.] Southern Med Univ, Nanfang Hosp, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China; [Hu, J. L.; He, G. Y.; Lan, X. L.; Zeng, Z. C.; Liao, W. T.; Ding, Y. Q.; Liang, L.] Southern Med Univ, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China; [Hu, J. L.; Zeng, Z. C.; Liao, W. T.; Ding, Y. Q.; Liang, L.] Guangdong Prov Key Lab Mol Tumor Pathol, Guangzhou 510515, Guangdong, Peoples R China; [He, G. Y.; Qian, X. L.] Xinxiang Med Univ, Dept Pathol, Xinxiang 453003, Henan, Peoples R China; [Lan, X. L.] Southern Med Univ, Nanfang Hosp, Dept Gen Surg, Guangzhou 510515, Guangdong, Peoples R China; [Guan, J.; Ding, Y.] Southern Med Univ, Nanfang Hosp, Dept Radiotherapy, Guangzhou 510515, Guangdong, Peoples R China		Liang, L (corresponding author), Southern Med Univ, Nanfang Hosp, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China.; Liang, L (corresponding author), Southern Med Univ, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China.	redsnow007@hotmail.com	liang, li/AAB-9126-2022		National Key R&D program of China [2017YFC1309002]; National Basic Research Program of China (973 Program)National Basic Research Program of China [2015CB554002]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672821, 81272759, 81472313, 81401927, 81773101]	This work was supported by the National Key R&D program of China (2017YFC1309002), National Basic Research Program of China (973 Program, 2015CB554002), and National Natural Science Foundation of China (81672821, 81272759, 81472313, 81401927, 81773101).	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J	Ranjbar, K; Ballaro, R; Bover, Q; Pin, F; Beltra, M; Penna, F; Costelli, P				Ranjbar, Kia; Ballaro, Riccardo; Bover, Quim; Pin, Fabrizio; Beltra, Marc; Penna, Fabio; Costelli, Paola			Combined Exercise Training Positively Affects Muscle Wasting in Tumor-Bearing Mice	MEDICINE AND SCIENCE IN SPORTS AND EXERCISE			English	Article						CANCER CACHEXIA; AEROBIC TRAINING; RESISTANCE TRAINING; AUTOPHAGY; PGC-1 alpha	RESISTANCE EXERCISE; CANCER CACHEXIA; ADIPOSE-TISSUE; MECHANISMS; PGC-1-ALPHA; PROGRESSION; ADAPTATION; PREVENTION; AUTOPHAGY; ATROPHY	Introduction Cancer cachexia is characterized by loss of muscle mass and function. Increased protein catabolism, inflammation, impaired anabolism, and mitochondrial function markedly contribute to the pathogenesis of this syndrome. Physical activity has been suggested as a useful tool to prevent or at least delay the onset and progression of cancer-induced muscle wasting. Two main types of exercise can be adopted, namely, resistance and endurance training. The present study is aimed to investigate the effectiveness of a combined (resistance + endurance) exercise protocol in preventing/reverting cancer-induced muscle wasting. Methods Mice bearing the C26 colon carcinoma have been used as a model of cancer cachexia. They have been exposed to combined exercise training during 6 wk (4 before tumor implantation, 2 during tumor growth). Climbing a 1-m ladder inclined at 85 degrees has been used for resistance training, while aerobic (endurance) exercise has been carried out on the same day using a motorized wheel. Results In C26-bearing mice, both muscle mass and strength are improved by combined training, while just the latter increased in exercised healthy animals. Such a pattern is associated with modulations of two markers of autophagy, namely, LC3B-I/II ratio, increased in sedentary tumor hosts and reduced in exercised C26-bearing mice, and p62, steadily increased in both sedentary and trained tumor-bearing animals. Finally, combined training is not able to modify PGC-1 alpha protein levels, but it improves succinate dehydrogenase activity, both reduced in the muscle of the C26 hosts. Conclusion The data reported in the present study show that combined training improves muscle mass and function in the C26 hosts, likely modulating autophagy and improving mitochondrial function; these observations suggest that combined exercise might become part of a multimodal approach to treat cancer cachexia.	[Ranjbar, Kia; Ballaro, Riccardo; Bover, Quim; Pin, Fabrizio; Beltra, Marc; Penna, Fabio; Costelli, Paola] Univ Turin, Dept Clin & Biol Sci, Corso Raffaello 30, I-10125 Turin, Italy; [Ranjbar, Kia] Tarbiat Modares Univ, Phys Educ & Sport Sci Dept, Tehran, Iran; [Ballaro, Riccardo; Beltra, Marc; Penna, Fabio; Costelli, Paola] Interuniv Inst Myol, Urbino, Italy; [Pin, Fabrizio] Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA		Costelli, P (corresponding author), Univ Turin, Dept Clin & Biol Sci, Corso Raffaello 30, I-10125 Turin, Italy.	paola.costelli@unito.it	Ballarò, Riccardo/ABC-1988-2020	Ballarò, Riccardo/0000-0001-5505-9024; Beltra Bach, Marc/0000-0001-6070-9861	University of Turin; Ministry of Science, Research and Technology, Islamic Republic of Iran	This work was supported by the University of Turin. K. Ranjbar was recipient of a scholarship funded by the Ministry of Science, Research and Technology, Islamic Republic of Iran. The authors are grateful to Dr. Conrad P. Earnest, Department of Health and Kinesiology, Texas A&M University, College Station, TX, for his critical discussion of results.	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J	Carew, JS; Giles, FJ; Nawrocki, ST				Carew, Jennifer S.; Giles, Francis J.; Nawrocki, Steffan T.			Histone deacetylase inhibitors: Mechanisms of cell death and promise in combination cancer therapy	CANCER LETTERS			English	Review						historic deacetylase inhibitor; apoptosis; autophagy; bortezomib; TRAIL	SUBEROYLANILIDE HYDROXAMIC ACID; HUMAN LEUKEMIA-CELLS; PROAPOPTOTIC PROTEIN BIM; HUMAN COLON-CANCER; INDUCED APOPTOSIS; HDAC INHIBITORS; PANCREATIC-CANCER; SODIUM-BUTYRATE; DOWN-REGULATION; SYNERGISTIC INDUCTION	Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression by catalyzing the removal of acetyl groups, stimulating chromatin condensation and promoting transcriptional repression. Since aberrant epigenetic changes are a hallmark of cancer, HDACs are a promising target for pharmacological inhibition. HDAC inhibitors can induce cell-cycle arrest, promote differentiation, and stimulate tumor cell death. These properties have prompted numerous preclinical and clinical investigations evaluating the potential efficacy of HDAC inhibitors for a variety of malignancies. The preferential toxicity of HDAC inhibitors in transformed cells and their ability to synergistically enhance the anticancer activity of many chemotherapeutic agents has further generated interest in this novel class of drugs. Here we summarize the different mechanisms of HDAC inhibitor-induced apoptosis and discuss their use in combination with other anticancer agents. (C) 2008 Elsevier Ireland Ltd. All rights reserved.	[Carew, Jennifer S.; Giles, Francis J.; Nawrocki, Steffan T.] Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78245 USA		Nawrocki, ST (corresponding author), Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, 14960 Omicron Dr, San Antonio, TX 78245 USA.	nawrocki@uthscsa.edu	qiao, zhixin/I-3408-2012		Institute for Drug Development, Cancer Therapy and Research Center at The Umversity of Texas Health Science Center at San Antonio	This work was supported by funding from The Institute for Drug Development, Cancer Therapy and Research Center at The Umversity of Texas Health Science Center at San Antonio.	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SEP 28	2008	269	1					7	17		10.1016/j.canlet.2008.03.037			11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	357LK	WOS:000259847100002	18462867				2022-04-25	
J	Zhang, YS; Wang, F; Cui, SX; Qu, XJ				Zhang, Yu-Sheng; Wang, Feng; Cui, Shu-Xiang; Qu, Xian-Jun			Natural dietary compound naringin prevents azoxymethane/dextran sodium sulfate-induced chronic colorectal inflammation and carcinogenesis in mice	CANCER BIOLOGY & THERAPY			English	Article						Colitis; colorectal carcinogenesis; Endoplasmic reticulum (ER) stress; autophagy; MDSCs; Naringin; Aspirin	SUPPRESSOR-CELLS; CANCER; DISEASE; DYSFUNCTION; AUTOPHAGY; COLITIS; RISK; ACTIVATION; APOPTOSIS; ASPIRIN	Naringin, a natural occurring flavonoid compound, enriches in citrus fruits. We aimed to evaluate the inhibitory effect of naringin on colitis and chronic inflammation-driven carcinogenesis. Male C57BL/6 mice were exposed to AOM/DSS to induce colorectal inflammation and carcinogenesis. Naringin by oral administration prevented AOM/DSS-induced ulcerative colitis and carcinogenesis without significant side effects. Naringin attenuated the severity of colitis and colorectal adenomas through inhibiting myeloid-derived suppressor cells (MDSCs), pro-inflammatory mediators GM-CSF/M-CSF, IL-6 and TNF-alpha and the NF-kappa B/IL-6/STAT3 cascades in colorectal tissues. Naringin-treated mice exhibited normalized structures of colorectal tissues. Electron microscopy analysis showed the suppression of robust endoplasmic reticulum (ER) stress-induced autophagy. Naringin inhibited the secretion of the ER-spanning transmembrane proteins, such as GRP78 ATF6, IRE1 alpha and activated PERK phosphorylated eIF-2 alpha and complex of autophagosomes ATG3, ATG5, ATG7, ATG12, ATG16 and ATG16L1 in the colorectal mucosal cells. Conclusion: Naringin prevented colitis and colorectal carcinogenesis through suppressing robust ER stress-induced autophagy in colorectal mucosal cells. Naringin could develop a promising therapeutic agent for the prevention of ulcerative colitis and colorectal tumor.	[Zhang, Yu-Sheng; Qu, Xian-Jun] Shandong Univ, Sch Pharmaceut Sci, Jinan, Shandong, Peoples R China; [Wang, Feng; Cui, Shu-Xiang] Capital Med Univ, Beijing Key Lab Environm Toxicol, Sch Publ Hlth, Dept Toxicol & Sanit Chem, Beijing, Peoples R China		Cui, SX; Qu, XJ (corresponding author), 10 You An Men Wai, Beijing 100069, Peoples R China.	sxccui@ccmu.edu.cn; qxj@sdu.edu.cn			Shandong Natural Science FoundationNatural Science Foundation of Shandong Province [ZR2009CQ019]; Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [91629303]	This project was supported by the Shandong Natural Science Foundation (ZR2009CQ019). This project was supported by the Natural Science Foundation of China (91629303).	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Ther.		2018	19	8					735	744		10.1080/15384047.2018.1453971			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GN9ZO	WOS:000439574300012	29580144	Green Published, Bronze			2022-04-25	
J	Sun, JW; Yang, JY; Chen, X; Li, L; Hao, J; Niu, H; Lai, MH; Qiu, S				Sun, Jian-Wei; Yang, Jing-Yu; Chen, Xin; Li, Li; Hao, Jie; Niu, Heng; Lai, Ming-Hua; Qiu, Shuang			Silencing of VMP1 makes breast cancer cells more aggressive and resistant to 5-Fu	INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE			English	Article						VMP1; breast cancer; lentivirus; chemotherapy; 5-Fu	BECLIN 1; AUTOPHAGY; EXPRESSION; COLON; METASTASIS; PATTERNS	Background: Vacuole membrane protein 1 (VMP1) was recently characterized to be involved in the process of cancer metastasis, and is also considered to play a vital role in balancing apoptosis and autophagy. Methods and results: Here, we evaluated the expression of VMP1 in 98 breast cancer and 54 matched adjacent noncancerous tissues with immunohistochemistry (IHC). The results showed a lower expression of VMP1 in advanced stages of breast cancer. Moreover, the patients with low expression of VMP1 were related to poor prognosis than those with high expression. Furthermore, to investigate whether the downregulation of VMP1 could confer malignant potential to breast cancer cells, we constructed and verified a lentivirus-based knockdown system to silence the expression of VMP1 in Michigan Cancer Foundation-7 cells (MCF7). After infection with lentivirus, the shVMP1 cells, which had VMP1 stably suppressed, gained significant aggressive properties of invasion and proliferation, and these mechanisms may relate to the activation of phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B(Akt)/zonulaoccludens-1 (ZO-1)/E-Cadherin pathway. On the other hand, we also found that shVMP1 cells were more sensitive to 5-Fluorouracil (5-Fu), but not cisplatin and oxaliplatin. Conclusions: In all, the above data suggest that patients with lower expression of VMP1 may have a poor prognosis, which may be ascribed to the more aggressive potential after down-regulation of VMP1 in breast cancer cells. In addition, these patients who have low expression of VMP1 may benefit from chemotherapy regimens containing 5-Fu.	[Sun, Jian-Wei; Yang, Jing-Yu; Chen, Xin; Li, Li; Hao, Jie; Niu, Heng; Lai, Ming-Hua; Qiu, Shuang] Kunming Univ Technol, Affiliated Hosp, Peoples Hosp Yunnan Prov 1, Dept Breast & Thyroid Surg, Kunming 650221, Yunnan, Peoples R China		Sun, JW (corresponding author), Kunming Univ Technol, Affiliated Hosp, Peoples Hosp Yunnan Prov 1, Dept Breast & Thyroid Surg, Kunming 650221, Yunnan, Peoples R China.	drsunjianwei@163.com					Acosta Karina B, 2011, Recent Pat DNA Gene Seq, V5, P175; Ando-Akatsuka Y, 1999, J CELL PHYSIOL, V179, P115, DOI 10.1002/(SICI)1097-4652(199905)179:2<115::AID-JCP1>3.0.CO;2-T; Dusetti NJ, 2002, BIOCHEM BIOPH RES CO, V290, P641, DOI 10.1006/bbrc.2001.6244; Giatromanolaki A, 2010, J CLIN PATHOL, V63, P867, DOI 10.1136/jcp.2010.079525; Gilabert M, 2013, J CELL PHYSIOL, V228, P1834, DOI 10.1002/jcp.24343; Grasso D, 2011, J BIOL CHEM, V286, P8308, DOI 10.1074/jbc.M110.197301; Guo L, 2012, CANCER SCI, V103, P2110, DOI 10.1111/cas.12025; Hu HK, 2011, SEMIN ONCOL, V38, P500, DOI 10.1053/j.seminoncol.2011.05.004; Huang XF, 2009, OBES REV, V10, P610, DOI 10.1111/j.1467-789X.2009.00607.x; Kenific CM, 2010, CURR OPIN CELL BIOL, V22, P241, DOI 10.1016/j.ceb.2009.10.008; Koukourakis MI, 2010, BRIT J CANCER, V103, P1209, DOI 10.1038/sj.bjc.6605904; Lattanzi A, 2014, HUM MOL GENET, V23, P3250, DOI 10.1093/hmg/ddu034; Liu Fen, 2013, Zhonghua Bing Li Xue Za Zhi, V42, P86, DOI 10.3760/cma.j.issn.0529-5807.2013.02.004; Miao YF, 2010, HEPATO-GASTROENTEROL, V57, P257; Mizushima N, 2007, GENE DEV, V21, P2861, DOI 10.1101/gad.1599207; Molejon MI, 2013, AUTOPHAGY, V9, P933, DOI 10.4161/auto.24390; Molejon MI, 2013, SCI REP-UK, V3, DOI 10.1038/srep01055; Okegawa T, 2002, J UROLOGY, V167, P1836, DOI 10.1016/S0022-5347(05)65245-7; Park JM, 2013, CANCER BIOL THER, V14, P100, DOI 10.4161/cbt.22954; Qian QY, 2014, BIOCHEM BIOPH RES CO, V443, P1041, DOI 10.1016/j.bbrc.2013.12.090; Sauermann M, 2008, ONCOGENE, V27, P1320, DOI 10.1038/sj.onc.1210743; Subramanya S, 2010, EXPERT OPIN BIOL TH, V10, P201, DOI 10.1517/14712590903448158; Wodarz A, 2007, NAT CELL BIOL, V9, P1016, DOI 10.1038/ncb433; Zhou Shi-quan, 2011, Zhonghua Yi Xue Za Zhi, V91, P2828	24	0	0	0	2	E-CENTURY PUBLISHING CORP	MADISON	40 WHITE OAKS LN, MADISON, WI 53711 USA	1940-5901			INT J CLIN EXP MED	Int. J. Clin. Exp. Med.		2019	12	11					13096	13107					12	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	JS4TZ	WOS:000500300700062					2022-04-25	
J	Mun, JG; Han, YH; Jeon, HD; Yoon, DH; Lee, YG; Hong, SH; Kee, JY				Mun, Jeong-Geon; Han, Yo-Han; Jeon, Hee-Dong; Yoon, Dae Hwan; Lee, Yeong Gyeong; Hong, Seung-Heon; Kee, Ji-Ye			Inhibitory Effect of Gallotannin on Lung Metastasis of Metastatic Colorectal Cancer Cells by Inducing Apoptosis, Cell Cycle Arrest and Autophagy	AMERICAN JOURNAL OF CHINESE MEDICINE			English	Article						GT; Metastatic Colorectal Cancer; Apoptosis; Cell Cycle Arrest; Autophagy	SENESCENCE; EXPRESSION; PATHWAY; AMPK; P53	Colorectal cancer (CRC) is the second most common cause of cancer death in the world, and metastatic CRC is a major cause of cancer death. Gallotannin (GT), a polyphenolic compound, has shown various biological effects such as anti-oxidant, anti-inflammatory, antimicrobial, and antitumor effects. However, the effects of GT on metastatic CRC cells are not completely understood. This study aimed to investigate the anti-metastatic effect of GT and the underlying mechanisms on metastatic CRC cells. Oral administration of GT suppressed the lung metastasis of metastatic CRC cells in the experimental mouse model. GT decreased the viability of metastatic CRC cell lines, including CT26, HCT116, and SW620, by inducing apoptosis through the activation of extrinsic and intrinsic pathways, cell cycle arrest through inactivation of CDK2/cyclin A complex, and autophagic cell death through up-regulation of LC3B and p62 levels. GT regulated PI3K/AKT/mTOR and AMPK signaling pathways, which are critical for the development and maintenance of cancer. Additionally, non-cytotoxic concentrations of GT can suppress migration and invasion of CRC cells by inhibiting the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and epithelial-mesenchymal transition by downregulating the expression of mesenchymal markers including snail, twist, and vimentin. In conclusion, GT prevented colorectal lung metastasis by reducing survival and inhibiting the metastatic phenotypes of CRC cells.	[Mun, Jeong-Geon; Han, Yo-Han; Jeon, Hee-Dong; Yoon, Dae Hwan; Lee, Yeong Gyeong; Hong, Seung-Heon; Kee, Ji-Ye] Wonkwang Univ, Coll Pharm, Wonkwang Oriental Med Res Inst, Dept Oriental Pharm, 460 Iksandae Ro, Iksan 54538, Jeonbuk, South Korea		Hong, SH; Kee, JY (corresponding author), Wonkwang Univ, Coll Pharm, Wonkwang Oriental Med Res Inst, Dept Oriental Pharm, 460 Iksandae Ro, Iksan 54538, Jeonbuk, South Korea.	jooklim@wku.ac.kr; keejy@wku.ac.kr			Wonkwang University	This study was supported by Wonkwang University in 2019.	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J. Chin. Med.		2021	49	06					1535	1555		10.1142/S0192415X21500725			21	Integrative & Complementary Medicine; Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	Integrative & Complementary Medicine; General & Internal Medicine	TP9ZS	WOS:000677950800012	34247563				2022-04-25	
J	Lee, YH; Chen, HY; Su, LJ; Chueh, PJ				Lee, Yi-Hui; Chen, Huei-Yu; Su, Lilly J.; Chueh, Pin Ju			Sirtuin 1 (SIRT1) Deacetylase Activity and NAD(+)/VNADH Ratio Are Imperative for Capsaicin-Mediated Programmed Cell Death	JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY			English	Article						apoptosis; autophagy; capsaicin; silent mating type information regulation 1 (sirtuin 1, SIRT1); tumor-associated NADH oxidase (tNOX, ENOX2)	ENDOPLASMIC-RETICULUM STRESS; PANCREATIC TUMOR-GROWTH; COLON-CANCER CELLS; IN-VITRO; SELECTIVE INDUCTION; TRANSFORMED-CELLS; SIGNALING PATHWAY; GENE-EXPRESSION; UP-REGULATION; APOPTOSIS	Capsaicin is considered a chemopreventive agent by virtue of its selective antigrowth activity, commonly associated with apoptosis, against cancer cells. However, noncancerous cells possess relatively higher tolerance to capsaicin, although the underlying mechanism for this difference remains unclear. Hence, this study aimed to elucidate the differential effects of capsaicin on cell lines from lung tissues by addressing the signal pathway leading to two types of cell death. In MRC-5 human fetal lung cells, capsaicin augmented silent mating type information regulation 1 (SIRT1) deacetylase activity and the intracellular NAD(+)/VNADH ratio, decreasing acetylation of p53 and inducing autophagy. In contrast, capsaicin decreased the intracellular NAD(+)/NADH ratio, possibly through inhibition of tumor-associated NADH oxidase (tNOX), and diminished SIRT1 expression leading to enhanced p53 acetylation and apoptosis. Moreover, SIRT1 depletion by RNA interference attenuated capsaicin-induced apoptosis in A549 cancer cells and autophagy in MRC-5 cells, suggesting a vital role for SIRT1 in capsaicin-mediated cell death. Collectively, these data not only explain the differential cytotoxicity of capsaicin but shed light on the distinct cellular responses to capsaicin in cancerous and noncancerous cell lines.	[Lee, Yi-Hui; Chen, Huei-Yu; Su, Lilly J.; Chueh, Pin Ju] Natl Chung Hsing Univ, Inst Biomed Sci, Taichung 40227, Taiwan; [Chueh, Pin Ju] China Med Univ, Grad Inst Basic Med, Taichung 40402, Taiwan; [Chueh, Pin Ju] China Med Univ Hosp, Dept Med Res, Taichung 40402, Taiwan; [Chueh, Pin Ju] Asia Univ, Dept Biotechnol, Taichung 41354, Taiwan		Chueh, PJ (corresponding author), Natl Chung Hsing Univ, Inst Biomed Sci, Taichung 40227, Taiwan.	pjchueh@dragon.nchu.edu.tw		Lee, YiHui/0000-0002-3690-6547; Chueh, Pin Ju/0000-0002-3200-7552			AGRAWAL RC, 1986, INT J CANCER, V38, P689, DOI 10.1002/ijc.2910380512; Amantini C, 2009, CARCINOGENESIS, V30, P1320, DOI 10.1093/carcin/bgp138; Archer VE, 2002, MED HYPOTHESES, V59, P450, DOI 10.1016/S0306-9877(02)00152-4; Asard H, 1998, PLASMA MEMBRANE REDO, P121, DOI DOI 10.1007/978-94-017-2695-5_5; Bley K, 2012, TOXICOL PATHOL, V40, P847, DOI 10.1177/0192623312444471; Bode AM, 2011, CANCER RES, V71, P2809, DOI 10.1158/0008-5472.CAN-10-3756; Chang TC, 2007, MOL CELL, V26, P745, DOI 10.1016/j.molcel.2007.05.010; 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Agric. Food Chem.	AUG 26	2015	63	33					7361	7370		10.1021/acs.jafc.5b02876			10	Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Agriculture; Chemistry; Food Science & Technology	CQ0XO	WOS:000360322100007	26255724				2022-04-25	
J	Zhou, N; Wei, ZX; Qi, ZX				Zhou, Nan; Wei, Zi Xuan; Qi, Zeng Xin			Inhibition of autophagy triggers melatonin-induced apoptosis in glioblastoma cells	BMC NEUROSCIENCE			English	Article						Melatonin; Agomelatine; Autophagy; Apoptosis; Glioma	GROWTH IN-VIVO; SIGNALING PATHWAYS; INDUCED CYTOTOXICITY; PINEAL HORMONE; PHASE-II; BECLIN 1; CANCER; EXPRESSION; RECEPTOR; PROTEIN	Background Autophagy is considered to be another restorative focus for the treatment of brain tumors. Although several research have demonstrated that melatonin induces autophagy in colon cancer and hepatoma cells, there has not been any direct evidence of whether melatonin is capable of inducing autophagy in human glioma cells. Results In the present research, we report that melatonin or its agonist, agomelatine, induced autophagy in A172 and U87-MG glioblastoma cells for a concentration-and time-dependent way, which was significantly attenuated by treatment with luzindole, a melatonin receptor antagonist. Furthermore, by suppressing autophagy at the late-stage with bafilomycin A1 and early stage with 3-MA, we found that the melatonin-induced autophagy was activated early, and the autophagic flux was complete. Melatonin treatment alone did not induce any apoptotic changes in the glioblastoma cells, as measured by flow cytometry. Western blot studies confirmed that melatonin alone prominently upregulated the levels of Beclin 1 and LC3 II, which was accompanied by an increase in the expression of Bcl-2, whereas it had no effect on the expression of Bax in the glioblastoma cells. Remarkably, co-treatment with 3-MA and melatonin significantly enhanced the apoptotic cell population in the glioblastoma cells, along with a prominent decrease in the expression of bcl-2 and increase in the Bax expression levels, which collectively indicated that the disruption of autophagy triggers the melatonin-induced apoptosis in glioblastoma cells. Conclusions These results provide information indicating that melatonin may act as a common upstream signal between autophagy and apoptosis, which may lead to the development of new therapeutic strategies for glioma.	[Zhou, Nan; Wei, Zi Xuan; Qi, Zeng Xin] Fudan Univ, Huashan Hosp, Dept Neurosurg, Middle Urumqi Rd 12, Shanghai 200040, Peoples R China		Qi, ZX (corresponding author), Fudan Univ, Huashan Hosp, Dept Neurosurg, Middle Urumqi Rd 12, Shanghai 200040, Peoples R China.	462644725@qq.com		Qi, Zengxin/0000-0001-5206-9948	Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81702461, 81702175]; Shanghai Sailing Programe [17YF1426500]	This study was supported by the Natural Science Foundation Grants (81702461, 81702175). Shanghai Sailing Programe (17YF1426500). The funder had no role in study design, data collection and analysis, decision to publish, or preparation request.	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DEC 23	2019	20	1							63	10.1186/s12868-019-0545-1			12	Neurosciences	Science Citation Index Expanded (SCI-EXPANDED)	Neurosciences & Neurology	KJ3XV	WOS:000511993300001	31870319	gold, Green Submitted, Green Published			2022-04-25	
J	Kim, YS; Lee, HJ; Park, JM; Han, YM; Kangwan, N; Oh, JY; Lee, DY; Hahm, KB				Kim, Yong Seok; Lee, Ho Jae; Park, Jong-Min; Han, Young-Min; Kangwan, Napapan; Oh, Ji Young; Lee, Dong Yoon; Hahm, Ki Baik			Targeted molecular ablation of cancer stem cells for curing gastrointestinal cancers	EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY			English	Review						Cancer stem cells; GI cancers; proton pump inhibitors; sonic hedgehog inhibitor; chloroquine; kimchi	EPITHELIAL-MESENCHYMAL TRANSITION; HELICOBACTER-PYLORI; SONIC-HEDGEHOG; GASTRIC-CANCER; SELF-RENEWAL; BARRETTS-ESOPHAGUS; POLARIZING ACTIVITY; INHIBITION; PREVENTION; GROWTH	Introduction: Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis.Areas covered: A novel approach to ablate CSCs in GI cancers, including esophageal, gastric, and colon cancers, is introduced along with explored underlying molecular mechanisms.Expert commentary: Though CSC ablation is still in the empirical stages and not in clinical practice, several strategies for ablating CSCs in GI cancers had been published, proton-pump inhibitors (PPIs) that regulate the membrane-bound ABC transporters, which underlie drug resistance; chloroquine (CQ) that inhibits autophagy, which is responsible for tumor survival; Hedgehog/Wnt/Notch inhibitors that influence the underlying stem-cell growth, and some natural products including Korean red ginseng, cancer-preventive kimchi, Artemisia extract, EGCG from green tea, and walnut extracts.	[Kim, Yong Seok; Hahm, Ki Baik] Hanyang Univ, Dept Biochem & Mol Biol, Coll Med, Seoul, South Korea; [Lee, Ho Jae] Gachon Univ, Dept Biochem, Coll Med, Incheon, South Korea; [Park, Jong-Min; Han, Young-Min; Hahm, Ki Baik] CHA Univ, CHA Canc Prevent Res Ctr, 59 Yatap Ro, Seongnam 463712, South Korea; [Kangwan, Napapan] Univ Phayao, Sch Med Sci, Div Physiol, Phayao, Thailand; [Oh, Ji Young; Lee, Dong Yoon] CJ Food, Suwon, South Korea; [Hahm, Ki Baik] CHA Univ, Ctr Digest Dis, Bundang Med Ctr, 59 Yatap Ro, Seongnam 463712, South Korea		Hahm, KB (corresponding author), CHA Univ, CHA Canc Prevent Res Ctr, 59 Yatap Ro, Seongnam 463712, South Korea.; Hahm, KB (corresponding author), CHA Univ, Ctr Digest Dis, Bundang Med Ctr, 59 Yatap Ro, Seongnam 463712, South Korea.	hahmkb@cha.ac.kr	; Kim, Yong-Seok/P-7501-2015	Kangwan, Napapan/0000-0002-9184-7850; Kim, Yong-Seok/0000-0001-5062-7408	Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through High Value-added Food Technology Development Program - Ministry of Agriculture, Food and Rural Affairs (MAFRA) [116015-03-1-CG000]	This research was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through High Value-added Food Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (116015-03-1-CG000).	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Gastroenterol. Hepatol.		2017	11	11					1059	1070		10.1080/17474124.2017.1356224			12	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	FM3VR	WOS:000414938300007	28707966				2022-04-25	
J	Marucci, G; Santinelli, C; Buccioni, M; Navia, AM; Lambertucci, C; Zhurina, A; Yli-Harja, O; Volpini, R; Kandhavelu, M				Marucci, Gabriella; Santinelli, Claudia; Buccioni, Michela; Navia, Aleix Marti; Lambertucci, Catia; Zhurina, Anastasia; Yli-Harja, Olli; Volpini, Rosaria; Kandhavelu, Meenakshisundaram			Anticancer activity study of A(3) adenosine receptor agonists	LIFE SCIENCES			English	Article						A(3) adenosine receptor; A(3) adenosine receptor ligands; Adenosine derivatives; Cancer cells; Signal activation; Apoptosis; Autophagy; Migration; Reactive oxygen species	CELL-LINE; IB-MECA; PROSTATE-CANCER; AUTOPHAGY; APOPTOSIS; TARGET; PROLIFERATION; DERIVATIVES; PHARMACOLOGY; MECHANISMS	Aims: A(3) adenosine receptor (A(3)AR) signalling activation seems to mediate anticancer effect, and it has been targeted for drug development. The identification of potent and selective A3AR agonists could be crucial for cancer drug development. Materials and methods: In the present study was determined the in vitro activity of known 1-3 and newly 4-6 synthesized compounds with high A(3)AR affinity and selectivity (K-i in the low nanomolar range) in binding studies. Effect of known and novel A(3)AR agonists on human prostate cancer (PC3), hepatocellular carcinoma (Hep G2), and epithelial colorectal carcinoma (Caco-2) cells were analysed by cytotoxicity assay, dose and time dependent inhibitor assay, migration, apoptosis, autophagy and reactive oxygen species (ROS) assays. Key findings: Results show that the anticancer effect is not due to A(3)AR activation alone. In fact, the more active and selective agonist versus A3AR, compound 1, results inactive on cancer cells such as compounds 2-4. Moreover, results show that the novel compound 5, at micromolar concentration range (IC50 = 28.0 mu M), inhibits the growth of PC3, Hep G2, and Caco-2 cells and their migration in time-and dose-dependent manner. The mechanism involved in cell death is attributable to apoptosis. At the same time compound 5 promotes autophagy, which induce apoptosis producing autophagic cell death. Further investigation revealed that compound 5 elevates the level of ROS in all cancer cells tested, suggesting the involvement of ROS in cell death. Significance: These results show that the new compound 5 exerts inhibitory effect on cancer cells through differential effect and may serve as a potential anticancer agent.	[Marucci, Gabriella; Santinelli, Claudia; Buccioni, Michela; Navia, Aleix Marti; Volpini, Rosaria] Univ Camerino, Sch Pharm, Via S Agostino 1, I-62032 Camerino, MC, Italy; [Santinelli, Claudia; Zhurina, Anastasia; Yli-Harja, Olli; Kandhavelu, Meenakshisundaram] Tampere Univ Technol, Fac Biomed Sci & Engn, Computat Syst Biol Res Grp, Mol Signaling Lab, POB 553, FIN-33101 Tampere, Finland; [Yli-Harja, Olli] Inst Syst Biol, 1441N 34th St, Seattle, WA 98103 USA		Kandhavelu, M (corresponding author), Tampere Univ Technol, Fac Biomed Sci & Engn, Computat Syst Biol Res Grp, Mol Signaling Lab, POB 553, FIN-33101 Tampere, Finland.	meenakshisundaram.kandhavelu@tut.fi	Kandhavelu, Meenakshisundaram/AAZ-7503-2021	Kandhavelu, Meenakshisundaram/0000-0002-4986-055X	Tampere University of Technology [85482, 85486]	MK and OYH acknowledge Tampere University of Technology (85482 and 85486) for Instrumental facility grant support. We also thank Prof. Matti Karp for providing the access to Fluorescence Plate reader instrumental facility at TUT.	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JUL 15	2018	205						155	163		10.1016/j.lfs.2018.05.028			9	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	GI3TK	WOS:000434293900018	29763615				2022-04-25	
J	Kim, JH; Kim, IW				Kim, Ju Hee; Kim, In-Wook			p62 manipulation affects chlorin e6-mediated photodynamic therapy efficacy in colorectal cancer cell lines	ONCOLOGY LETTERS			English	Article						p62; colorectal cancer; therapeutic agents; apoptosis; tumor genesis; autophagy	INDUCED APOPTOSIS; AUTOPHAGY; INHIBITION; RESISTANCE; P62/SQSTM1; PATHWAY; PHOTOSENSITIZER; MECHANISMS; SURVIVAL; PROTEIN	p62 is a multifunctional protein that mediates cell signaling pathways, autophagy and tumorigenesis, and participates in important regulation processes at the intersection between autophagy and cancer. Photodynamic therapy (PDT) is a treatment that involves photosensitizing agents and light to kill cancer cells. However, whether the efficacy of PDT depends on the expression level of p62 in colorectal cancer cell lines is not known. The present study aimed to examine the role of p62 expression levels in chlorin e6-based PDT in colorectal cancer cells. To study the effect of p62 on cancer cell death, we used PDT to treat a stable cell line overexpressing p62. Cells overexpressing p62 showed a higher cell death rate than cells not expressing this protein. Overexpression of p62 may contribute to colorectal cancer cell death. These results provide preliminary evidence for use of p62 as a therapy target to treat colorectal cancer.	[Kim, Ju Hee] Seoul Natl Univ Hosp, Biomed Res Inst, Seoul 03080, South Korea; [Kim, In-Wook] Hanyang Univ, Coll Engn, Dept Bioengn, 222 Wangsimni Ro, Seoul 04763, South Korea		Kim, IW (corresponding author), Hanyang Univ, Coll Engn, Dept Bioengn, 222 Wangsimni Ro, Seoul 04763, South Korea.	iwkim@hanyang.ac.kr	Kim, In-Wook/AAN-8123-2020	Kim, In-Wook/0000-0002-5501-2928	Basic Science Research Program through The National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF-2017R1A2B4011122, NRF-2019R1C1C1006898]	The present study was supported by The Basic Science Research Program through The National Research Foundation of Korea (NRF) funded by The Ministry of Education, Science and Technology (grant nos. NRF-2017R1A2B4011122 and NRF-2019R1C1C1006898).	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Lett.	JUN	2020	19	6					3907	3916		10.3892/ol.2020.11522			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	LR6CN	WOS:000535780700031	32391099	Green Published, gold			2022-04-25	
J	Liang, CY; Sir, D; Lee, S; Ou, JHJ; Jung, JU				Liang, Chengyu; Sir, Donna; Lee, Steven; Ou, Jing-hsiung James; Jung, Jae U.			Beyond autophagy	AUTOPHAGY			English	Article						UVRAG; the class C Vps complex; autophagy; autophagosome maturation; membrane trafficking	C-VPS COMPLEX; MAMMALIAN-CELLS; PROTEIN-TRANSPORT; SELF-DIGESTION; COLON-CANCER; UVRAG; MATURATION; VACUOLE; DISEASE; FUSION	Autophagy is a lysosome-directed membrane trafficking event for the degradation of cytoplasmic components, including organelles. The past few years have seen a great advance in our understanding of the cellular machinery of autophagosome biogenesis, the hallmark of autophagy. However, our global understanding of autophagosome maturity remains relatively poor and fragmented. The topological similarity of autophagosome and endosome delivery to lysosomes suggests that autophagic and endosomal maturation may have evolved to share associated machinery to promote the lysosomal delivery of their cargoes. We have recently discovered that UVRAG, originally identified as a Beclin 1-binding autophagy protein, appears to be an important factor in autophagic and endosomal trafficking through its interaction with the class C Vps tethering complex. Given the ability of UVRAG to bind Beclin I and the class C Vps complex in a genetically and functionally separable manner, it may serve as an important regulator for the spatial and/or temporal control of diverse cellular trafficking events. As more non-autophagic functions of UVRAG are unveiled, our understanding of seemingly different cellular processes may move a step further.	[Liang, Chengyu; Sir, Donna; Lee, Steven; Ou, Jing-hsiung James; Jung, Jae U.] Univ So Calif, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA		Liang, CY (corresponding author), Univ So Calif, Dept Mol Microbiol & Immunol, Room 5517,MC NRT 9605,1450 Biggy St, Los Angeles, CA 90033 USA.	chengyu.liang@usc.edu		LIANG, CHENGYU/0000-0001-6082-2143	U.S. Public Health ServiceUnited States Department of Health & Human ServicesUnited States Public Health Service [CA82057, CA91819, CA31363, CA106156, RR00168]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA082057, R01CA031363, R01CA091819, R01CA106156] Funding Source: NIH RePORTER; NATIONAL CENTER FOR RESEARCH RESOURCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [P51RR000168, K26RR000168] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01AI073099] Funding Source: NIH RePORTER	We would like to thank B. Levine, M.J. Hardwick, S. Virgin, S. Field, T Yoshimori and Y. Ohsumi for providing reagents. We also thank Steven Lee for proofreading. This work was partly supported by U.S. Public Health Service grants CA82057, CA91819, CA31363, CA106156, RR00168 (J.U.J.). C.L. is a Leukemia & Lymphoma Society Fellow.	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J	Zhao, Z; Xia, GG; Li, N; Su, RP; Chen, X; Zhong, L				Zhao, Zhi; Xia, Guanggai; Li, Ni; Su, Ruping; Chen, Xiao; Zhong, Li			Autophagy Inhibition Promotes Bevacizumab-induced Apoptosis and Proliferation Inhibition in Colorectal Cancer Cells	JOURNAL OF CANCER			English	Article						Autophagy; Anti-VEGF; Bevacizumab; Colorectal cancer	ANTIANGIOGENIC THERAPY; ANGIOGENESIS INHIBITION; OVARIAN-CANCER; LUNG-CANCER; METASTASIS; EXPRESSION	Aim: Anti-VEGF therapy plays an important role in the treatment of malignant tumors, especially metastatic malignant tumors. However, resistance and an inefficient response to anti-VEGF therapy exist. The current study aimed to investigate whether autophagy plays a part in the anti-tumor effect of bevacizumab in colorectal cancer cells. Methods: VEGF-A expression was measured by immunohistochemical methods. Cell viability and cell apoptosis were detected using 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and flow cytometry. Autophagy was assessed by a western blot, fluorescence microscopy and transmission electron microscopy. HIF-1 alpha was measured using a western blot. A xenograft tumor model of colorectal cancer was constructed to determine the efficacy of the treatment of bevacizumab and chloroquine. Results: VEGF-A protein was upregulated in colorectal cancer tissue. Anti-VEGF (bevacizumab) inhibited cell viability and induced apoptosis. Moreover, bevacizumab induced autophagy. The inhibition of autophagy by chloroquine or by small interfering RNA promoted bevacizumab-induced apoptosis and proliferation inhibition. Further study showed that bevacizumab treatment significantly augmented HIF-la. Furthermore, cells pretreated with YC-1, a HIF-1 alpha inhibitor, displayed significantly attenuated bevacizumab-induced autophagy. Finally, a combinatory treatment of bevacizumab and chloroquine synergistically inhibited tumor growth in a xenograft tumor model of colorectal cancer cells. Conclusions: Our results showed that the inhibition of autophagy promoted the anti-tumor effect of bevacizumab and may offer a promising therapeutic strategy for colorectal cancer.	[Zhao, Zhi; Su, Ruping; Chen, Xiao; Zhong, Li] Peoples Hosp Guilin, Dept Gastrointestinal & Hernia Surg, Guilin 541002, Peoples R China; [Xia, Guanggai] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Gen Surg, Shanghai 200233, Peoples R China; [Li, Ni] Peoples Hosp Guilin, Hlth Management Ctr, Guilin 541002, Peoples R China		Zhong, L (corresponding author), Peoples Hosp Guilin, Dept Gastrointestinal & Hernia Surg, Guilin 541002, Peoples R China.	Zhongli0302@163.com			Wu Jieping medical fund [320.6750.13390]	This study was supported by the Wu Jieping medical fund (No. 320.6750.13390).	Chebib R, 2017, SEMIN ONCOL, V44, P114, DOI 10.1053/j.seminoncol.2017.07.004; Ebos JML, 2011, NAT REV CLIN ONCOL, V8, P210, DOI 10.1038/nrclinonc.2011.21; Giampieri R, 2016, CRIT REV ONCOL HEMAT, V100, P99, DOI 10.1016/j.critrevonc.2016.02.005; Gomez-Sintes R, 2017, CELLS, V22, P1; Gui L, 2016, EXP THER MED, V11, P2233, DOI 10.3892/etm.2016.3190; Islami F, 2018, CA-CANCER J CLIN, V68, P31, DOI 10.3322/caac.21440; Jain RK, 2017, UROL ONCOL-SEMIN ORI, V35, P640, DOI 10.1016/j.urolonc.2017.08.010; Jemal A, 2010, CANCER EPIDEM BIOMAR, V19, P1893, DOI 10.1158/1055-9965.EPI-10-0437; Kerbel RS, 2015, CANCER J, V21, P274, DOI 10.1097/PPO.0000000000000134; Mahecha AM, 2017, ONCOTARGETS THER, V10, P4617, DOI 10.2147/OTT.S132558; Mohamed SY, 2017, J GASTROINTEST CANC, V5, P1; Ngabire D, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18092016; Poillet-Perez L, 2015, REDOX BIOL, V4, P184, DOI 10.1016/j.redox.2014.12.003; Rubatt JM, 2009, GYNECOL ONCOL, V112, P469, DOI 10.1016/j.ygyno.2008.11.030; Sathornsumetee S, 2007, CURR PHARM DESIGN, V13, P3545, DOI 10.2174/138161207782794130; Selvakumaran M, 2013, CLIN CANCER RES, V19, P2995, DOI 10.1158/1078-0432.CCR-12-1542; Shen ZT, 2017, CELL DEATH DIS, V8, DOI 10.1038/s41419-017-0048-x; Stratigos M, 2016, TRANSL LUNG CANCER R, V5, P389, DOI 10.21037/tlcr.2016.08.04; Torre LA, 2015, CA-CANCER J CLIN, V65, P87, DOI 10.3322/caac.21262; van Beijnum JR, 2015, PHARMACOL REV, V67, P441, DOI 10.1124/pr.114.010215; Vasudev NS, 2014, ANGIOGENESIS, V17, P471, DOI 10.1007/s10456-014-9420-y; White E, 2015, CLIN CANCER RES, V21, P5037, DOI 10.1158/1078-0432.CCR-15-0490; White E, 2015, J CLIN INVEST, V125, P42, DOI 10.1172/JCI73941; Zhan P, 2009, J THORAC ONCOL, V4, P1094, DOI 10.1097/JTO.0b013e3181a97e31; Zhao Z, 2015, CANCER LETT, V358, P17, DOI 10.1016/j.canlet.2014.11.046; Zhu J, 2017, AM J TRANSL RES, V9, P4046	26	18	21	3	7	IVYSPRING INT PUBL	LAKE HAVEN	PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA	1837-9664			J CANCER	J. Cancer		2018	9	18					3407	3416		10.7150/jca.24201			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GS9DJ	WOS:000444015800024	30271503	Green Published, Green Submitted, gold			2022-04-25	
J	Kurdi, A; Cleenewerck, M; Vangestel, C; Lyssens, S; Declercq, W; Timmermans, JP; Stroobants, S; Augustyns, K; De Meyer, GRY; Van Der Veken, P; Martinet, W				Kurdi, Ammar; Cleenewerck, Matthias; Vangestel, Christel; Lyssens, Sophie; Declercq, Wim; Timmermans, Jean-Pierre; Stroobants, Sigrid; Augustyns, Koen; De Meyer, Guido R. Y.; Van Der Veken, Pieter; Martinet, Wim			ATG4B inhibitors with a benzotropolone core structure block autophagy and augment efficiency of chemotherapy in mice	BIOCHEMICAL PHARMACOLOGY			English	Article						ATG4B; Autophagy; Osmotic minipump; Colorectal tumor; Benzotropolone	ADVANCED SOLID TUMORS; PHASE-I TRIAL; BREAST-CANCER; THERAPEUTIC TARGET; RADIATION-THERAPY; CARCINOMA-CELLS; HYDROXYCHLOROQUINE; MTOR; RESISTANCE; MECHANISM	Autophagy is a cell survival mechanism hijacked by advanced tumors to endure a rough microenvironment. Late autophagy inhibitors such as (hydroxy)chloroquine have been used clinically to halt tumor progression with modest success. However, given the toxic nature of these compounds and their lack of specificity, novel targets should be considered. We recently identified a benzotropolone derivative that significantly inhibited the essential autophagy protein ATG4B. Therefore, we synthesized and tested additional benzotropolone compounds to identify a promising ATG4B inhibitor that impairs autophagy both in vitro and in vivo. A compound library containing 27 molecules with a benzotropolone backbone was synthesized and screened for inhibition of recombinant ATG4B. Depending on the benzotropolone compound, inhibition of recombinant ATG4B ranged from 3 to 82%. Active compounds were evaluated in cellular assays to confirm inhibition of ATG4B and suppression of autophagy. Seven compounds inhibited processing of the autophagy protein LC3 and autophagosome formation. Compound UAMC-2526 was selected for further in vivo use because of its fair plasma stability. This compound abolished autophagy both in nutrient-deprived GFP-LC3 mice and in CD1(-/-) Foxn1nu mice bearing HT29 colorectal tumor xenografts. Moreover, addition of UAMC-2526 to the chemotherapy drug oxaliplatin significantly improved inhibition of tumor growth. Our data indicate that suppression of autophagy via ATG4B inhibition is a feasible strategy to augment existing chemotherapy efficacy and to halt tumor progression. (C) 2017 Elsevier Inc. All rights reserved.	[Kurdi, Ammar; De Meyer, Guido R. Y.; Martinet, Wim] Univ Antwerp, Dept Pharmaceut Sci, Lab Physiopharmacol, Antwerp, Belgium; [Cleenewerck, Matthias; Lyssens, Sophie; Augustyns, Koen; Van Der Veken, Pieter] Univ Antwerp, Dept Pharmaceut Sci, Lab Med Chem UAMC, Antwerp, Belgium; [Vangestel, Christel; Stroobants, Sigrid] Univ Antwerp, MICA, Antwerp, Belgium; [Declercq, Wim] VIB Inflammat Res Ctr, Ghent, Belgium; [Declercq, Wim] Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium; [Timmermans, Jean-Pierre] Univ Antwerp, Dept Vet Sci, Lab Cell Biol & Histol, Antwerp, Belgium		Martinet, W (corresponding author), Univ Antwerp, Lab Physiopharmacol, Univ Pl 1, B-2610 Antwerp, Belgium.	wim.martinet@uantwerpen.be	Augustyns, Koen/ABG-2306-2020; De Meyer, Guido/R-8129-2016; Martinet, Wim/I-7375-2015; Augustyns, Koen/C-1102-2008; Van der Veken, Pieter/P-5819-2016	Augustyns, Koen/0000-0002-5203-4339; De Meyer, Guido/0000-0003-3848-8702; Martinet, Wim/0000-0003-1967-9343; Augustyns, Koen/0000-0002-5203-4339; Van der Veken, Pieter/0000-0003-1208-3571; Stroobants, Sigrid/0000-0002-6450-9944	Fund for Scientific Research (FWO)-FlandersFWO [G.0431.11, G.0412.16N]; University of Antwerp (BOF); Stichting tegen Kanker [2016/868]	This work was supported by the Fund for Scientific Research (FWO)-Flanders (projects G.0431.11 and G.0412.16N), the University of Antwerp (BOF) and Stichting tegen Kanker (2016/868 to W.D.). The FEI Tecnai transmission electron microscope was purchased with support of the Hercules Foundation. The authors thank Dr. Noboru Mizushima (Tokyo Medical and Dental University, Japan) for GFP-LC3 mice, Dr. Robin Ketteler (MRC Laboratory for Molecular Cell Biology, UK) for pEAK12 plasmid DNA encoding beta-actine-LC3-dNGLUC and Dr. Nobuo N. Noda (Hokkaido University, Japan) for LC3B-GST and ATG4B plasmids. We also acknowledge Rita Van Den Bossche, Hermine Fret, Anne-Elise Van Hoydonck, Ria Roelandt, Carine Moers and Francis Terloo for excellent technical support. We dedicate this paper to our colleague, Prof Sandra Apers, who passed away much too early on February 5th, 2017.	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Pharmacol.	AUG 15	2017	138						150	162		10.1016/j.bcp.2017.06.119			13	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	FB4BO	WOS:000406086700014	28642033	Green Accepted			2022-04-25	
J	Ishima, Y; Inoue, A; Fang, J; Kinoshita, R; Ikeda, M; Watanabe, H; Maeda, H; Otagiri, M; Maruyama, T				Ishima, Yu; Inoue, Aki; Fang, Jun; Kinoshita, Ryo; Ikeda, Mayumi; Watanabe, Hiroshi; Maeda, Hiroshi; Otagiri, Masaki; Maruyama, Toru			Poly-S-nitrosated human albumin enhances the antitumor and antimetastasis effect of bevacizumab, partly by inhibiting autophagy through the generation of nitric oxide	CANCER SCIENCE			English	Article						Autophagy; bevacizumab; drug resistance; nitric oxide; SNO-HSA	HUMAN SERUM-ALBUMIN; PHASE-II TRIAL; CANCER; TUMOR; MECHANISM; DRUG; ANGIOGENESIS; IRINOTECAN; RESISTANCE; DELIVERY	Autophagy is one of the major causes of drug resistance. For example, the angiogenesis inhibitor bevacizumab shows only transient and short-term therapeutic effects, whereas long-term therapeutic benefits are rarely observed, probably due to hypoxia-induced autophagy. Nitric oxide (NO) is an important molecule with multiple functions, and it has recently been reported to function as a regulator of autophagy. Therefore, a reasonable therapeutic strategy for overcoming drug resistance by NO would involve it being directly delivered to the tumor. Here, we investigated the inhibitory effect of NO on autophagy by using a macromolecular NO donor S-nitrosated human serum albumin (SNO-HSA) with a high degree of NO loading and tumor targeting potential. In colon 26 (C26) cells, SNO-HSA significantly suppressed hypoxia-induced autophagy by inhibiting the phosphorylation of JNK1 and the expression of its downstream molecule Beclin1. The effect of SNO-HSA was also confirmed in vivo by combining it with Bev. In C26-bearing mice, significant suppression of tumor growth as well as lung metastasis was achieved in the combination group compared to the SNO-HSA or bevacizumab alone group. Similar to the in vitro experiments, the immunostaining of tumor tissues clearly showed that SNO-HSA inhibited the autophagy of tumor cells induced by bevacizumab treatment. In addition to other known antitumor effects of SNO-HSA, that is, the induction of apoptosis and the inhibition of multidrug efflux pumps, these data may open alternate strategies for cancer chemotherapy by taking advantage of the ability of SNO-HSA to suppress autophagy-mediated drug resistance and enhance the efficacy of chemotherapy.	[Ishima, Yu; Inoue, Aki; Kinoshita, Ryo; Ikeda, Mayumi; Watanabe, Hiroshi; Maruyama, Toru] Kumamoto Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut, Kumamoto 8620973, Japan; [Ishima, Yu; Watanabe, Hiroshi; Maruyama, Toru] Kumamoto Univ, Ctr Clin Pharmaceut Sci, Kumamoto 8620973, Japan; [Fang, Jun; Otagiri, Masaki] Sojo Univ, Fac Pharmaceut Sci, Kumamoto, Japan; [Maeda, Hiroshi; Otagiri, Masaki] Sojo Univ, DDS Res Inst, Kumamoto, Japan		Maruyama, T (corresponding author), Kumamoto Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut, 5-1 Oe Honmachi, Kumamoto 8620973, Japan.	tomaru@gpo.kumamoto-u.ac.jp	Maeda, Hiroshi/N-4471-2016	Ikeda-Imafuku, Mayumi/0000-0002-7254-3050	Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science; Ministry of Education, Culture, Sports, Science and Technology, JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [Kakenhi 25860118, 23390142, 21390177]; Uehara Memorial FoundationUehara Memorial Foundation; Yasuda Medical Foundation	This work was supported in part by Grants-in-Aid from the Japan Society for the Promotion of Science and Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (Kakenhi 25860118, 23390142, and 21390177), Japan. The work was also supported in part by grants from the Uehara Memorial Foundation and the Yasuda Medical Foundation.	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FEB	2015	106	2					194	200		10.1111/cas.12577			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CC2JJ	WOS:000350171000009	25457681	gold, Green Published			2022-04-25	
J	Zhang, CY; Sun, J; Wang, X; Wang, CF; Zeng, XD				Zhang, Chun-Yang; Sun, Jie; Wang, Xing; Wang, Cui-Fang; Zeng, Xian-Dong			Clinicopathological significance of human leukocyte antigen F-associated transcript 10 expression in colorectal cancer	WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY			English	Article						Colorectal cancer; Ubiquitin; Ubiquitin-like proteins; Human leukocyte antigen F-associated transcript 10; p53	UBIQUITIN-LIKE PROTEIN; ENDOSCOPIC ULTRASOUND; HEPATOCELLULAR-CARCINOMA; MODIFIER FAT10; TUMOR; AUTOPHAGY; P53; PHOSPHORYLATION; METASTASIS; APOPTOSIS	BACKGROUND Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract. The worldwide mortality rate of CRC is about one half of its morbidity. Ubiquitin is a key regulatory factor in the cell cycle and widely exists in eukaryotes. Human leukocyte antigen F-associated transcript 10 (FAT10), known as diubiquitin, is an 18 kDa protein with 29% and 36% homology with the N and C termini of ubiquitin. The function of FAT10 has not been fully elucidated, and some studies have shown that it plays an important role in various cell processes. AIM To examine FAT10 expression and to analyze the relationship between FAT10 expression and the clinicopathological parameters of CRC. METHODS FAT10 expression in 61 cases of CRC and para-cancer colorectal tissues was measured by immunohistochemistry and Western blotting. The relationship between FAT10 expression and clinicopathological parameters of CRC was statistically analyzed. RESULTS Immunohistochemical analysis showed that the positive rate of FAT10 expression in CRC (63.93%) was significantly higher than that in tumor-adjacent tissues (9.84%, P < 0.05) and normal colorectal mucosal tissue (1.64%, P < 0.05). Western blotting also indicated that FAT10 expression was significantly higher in CRC than in tumor-adjacent tissue (P < 0.05). FAT10 expression was closely associated with clinical stage and lymphatic spread of CRC. FAT10 expression also positively correlated with p53 expression. CONCLUSION FAT10 expression is highly upregulated in CRC. FAT10 expression is closely associated with clinical stage and lymphatic spread of CRC.	[Zhang, Chun-Yang] Shenyang Med Coll, Cent Hosp, Dept Emergency Med, Shenyang 110024, Liaoning, Peoples R China; [Sun, Jie; Wang, Xing; Wang, Cui-Fang] Shenyang Med Coll, Cent Hosp, Dept Pathol, Shenyang 110024, Liaoning, Peoples R China; [Zeng, Xian-Dong] Shenyang Med Coll, Cent Hosp, Dept Surg Oncol, 5 South Seven West Rd, Shenyang 110024, Liaoning, Peoples R China		Zeng, XD (corresponding author), Shenyang Med Coll, Cent Hosp, Dept Surg Oncol, 5 South Seven West Rd, Shenyang 110024, Liaoning, Peoples R China.	1403973708@qq.com					Aichem A, 2016, INT J BIOCHEM CELL B, V79, P451, DOI 10.1016/j.biocel.2016.07.001; Aichem A, 2012, J CELL SCI, V125, P4576, DOI 10.1242/jcs.107789; Altun M, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0115344; Basler M, 2015, MOL IMMUNOL, V68, P129, DOI 10.1016/j.molimm.2015.04.012; Bhutani MS, 2016, ENDOSC ULTRASOUND, V5, P85, DOI 10.4103/2303-9027.180471; Cajee UF, 2012, INT J MOL SCI, V13, P11804, DOI 10.3390/ijms130911804; Cartana ET, 2018, ENDOSC ULTRASOUND, V7, P175, DOI 10.4103/eus.eus_7_17; Chen WQ, 2016, CA-CANCER J CLIN, V66, P115, DOI 10.3322/caac.21338; Ersan V, 2017, J TRANSL INTERN MED, V5, P186, DOI 10.1515/jtim-2017-0026; Eshtiaghpour D, 2016, ENDOSC ULTRASOUND, V5, P196, DOI 10.4103/2303-9027.183980; Gao Y, 2015, BIOL OPEN, V4, P961, DOI 10.1242/bio.011189; Gao Y, 2014, CARCINOGENESIS, V35, P923, DOI 10.1093/carcin/bgt407; Gatti M, 2015, CELL REP, V10, P226, DOI 10.1016/j.celrep.2014.12.021; Hospenthal MK, 2015, NAT PROTOC, V10, P349, DOI 10.1038/nprot.2015.018; Jain CK, 2015, RECENT PAT ANTI-CANC, V10, P201, DOI 10.2174/1574892810666150416111213; Jentsch S, 2000, TRENDS CELL BIOL, V10, P335, DOI 10.1016/S0962-8924(00)01785-2; Ji F, 2009, WORLD J GASTROENTERO, V15, P2228, DOI 10.3748/wjg.15.2228; Lee CGL, 2003, ONCOGENE, V22, P2592, DOI 10.1038/sj.onc.1206337; Lim CB, 2006, CELL DIV, V1, DOI 10.1186/1747-1028-1-20; Liu YC, 1999, P NATL ACAD SCI USA, V96, P4313, DOI 10.1073/pnas.96.8.4313; Lukasiak S, 2008, ONCOGENE, V27, P6068, DOI 10.1038/onc.2008.201; Maclaine NJ, 2009, AGING-US, V1, P490, DOI 10.18632/aging.100047; Madsen L, 2007, BMC BIOCHEM, V8, DOI 10.1186/1471-2091-8-S1-S1; Malmstrom ML, 2016, ENDOSC ULTRASOUND, V5, P307, DOI 10.4103/2303-9027.191610; Merbl Y, 2013, CELL, V152, P1160, DOI 10.1016/j.cell.2013.02.007; Montagnani F, 2017, J TRANSL INTERN MED, V5, P18, DOI 10.1515/jtim-2017-0005; Murdoch JD, 2016, CELL REP, V17, P1071, DOI 10.1016/j.celrep.2016.09.058; Ponder EL, 2007, EUKARYOT CELL, V6, P1943, DOI 10.1128/EC.00282-07; Ren JW, 2011, J CELL SCI, V124, P3665, DOI 10.1242/jcs.087403; Schmidtke G, 2014, BBA-MOL CELL RES, V1843, P97, DOI 10.1016/j.bbamcr.2013.01.009; Theng SS, 2014, P NATL ACAD SCI USA, V111, pE5282, DOI 10.1073/pnas.1403383111; Wang YQ, 2017, J TRANSL INTERN MED, V5, P135, DOI 10.1515/jtim-2017-0029; Wauer T, 2015, EMBO J, V34, P307, DOI 10.15252/embj.201489847; Wu D, 2017, J TRANSL INTERN MED, V5, P4, DOI 10.1515/jtim-2017-0008; Xie XQ, 2015, AUTOPHAGY, V11, P1775, DOI 10.1080/15548627.2015.1082025; Yang Z, 2015, CELL IMMUNOL, V293, P17, DOI 10.1016/j.cellimm.2014.11.003; Yuan RF, 2014, CANCER RES, V74, P5287, DOI 10.1158/0008-5472.CAN-14-0284; Zhang DW, 2006, ONCOGENE, V25, P2318, DOI 10.1038/sj.onc.1209220	38	5	6	1	2	BAISHIDENG PUBLISHING GROUP INC	PLEASANTON	8226 REGENCY DR, PLEASANTON, CA 94588 USA	1948-5204			WORLD J GASTRO ONCOL	World J. Gastrointest. Oncol.	JAN 15	2019	11	1					9	16		10.4251/wjgo.v11.i1.9			8	Oncology; Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Gastroenterology & Hepatology	HH7NH	WOS:000455917100002	30984346	Green Published, Green Submitted, hybrid			2022-04-25	
J	Tam, SY; Wu, VWC; Law, HKW				Tam, Shing Yau; Wu, Vincent W. C.; Law, Helen K. W.			Dynamics of oxygen level-driven regulators in modulating autophagy in colorectal cancer cells	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						Autophagy; Autophagy regulator; Colorectal cancer cell; Hypoxia; Oxygen level	HYPOXIA; BNIP3; AMPK	Colorectal cancer is a common cancer with metachronous distant metastases still threatening overall survival. Tumor oxygen level influences tumor radiosensitivity in relation to autophagy and apoptosis. The objective of this study is to evaluate the expression and interaction between multiple key regulators in different oxygen levels. Human colorectal adenocarcinoma HT-29 cells were cultured in 1% or 10% oxygen level and irradiated by 2 Gy with different incubation time. Autophagy key regulators, AMPK, HIFs and JNK were evaluated by Western blot. Sequential autophagy key regulator activation was observed in the order of AMPK, HIF-1 alpha, HIF-2 alpha and JNK. 10% oxygen level could promote autophagy with similar degree of autophagy activation as 1% oxygen level in 48-h while irradiation could slightly inhibit autophagy. The results of this study supported prior evaluation of oxygen level and autophagy regulators for improving treatment efficacy and indicated the possible directions in developing individualized radiotherapy by selective targeting of hypoxic regions. (C) 2019 The Authors. Published by Elsevier Inc.	[Tam, Shing Yau; Wu, Vincent W. C.; Law, Helen K. W.] Hong Kong Polytech Univ, Fac Hlth & Social Sci, Dept Hlth Technol & Informat, Hung Hom, Hong Kong, Peoples R China		Wu, VWC; Law, HKW (corresponding author), Hong Kong Polytech Univ, Fac Hlth & Social Sci, Dept Hlth Technol & Informat, Hung Hom, Hong Kong, Peoples R China.	shing-yau.tam@connect.polyu.hk; htvinwu@polyu.edu.hk; hthelen@polyu.edu.hk	Tam, Shing Yau/AAN-4109-2020; Tam, Shing Yau/AAZ-1345-2020	Tam, Shing Yau/0000-0002-5899-1041	Hong Kong Polytechnic UniversityHong Kong Polytechnic University	This research was supported by Postgraduate Studentship to S.T. and Internal grants (G-YBPL, and HTI-GRF Seeding Fund for H.L.) from The Hong Kong Polytechnic University.	Bellot G, 2009, MOL CELL BIOL, V29, P2570, DOI 10.1128/MCB.00166-09; Bracken CP, 2006, J BIOL CHEM, V281, P22575, DOI 10.1074/jbc.M600288200; Braunstein S, 2007, MOL CELL, V28, P501, DOI 10.1016/j.molcel.2007.10.019; Chao MW, 2015, ONCOTARGET, V6, P24092, DOI 10.18632/oncotarget.4483; Erler JT, 2004, MOL CELL BIOL, V24, P2875, DOI 10.1128/MCB.24.7.2875-2889.2004; Faubert B, 2013, CELL METAB, V17, P113, DOI 10.1016/j.cmet.2012.12.001; Ferlay J, 2015, INT J CANCER, V136, pE359, DOI 10.1002/ijc.29210; Fiebig AA, 2006, BMC CANCER, V6, DOI 10.1186/1471-2407-6-213; Hill RP, 2015, SEMIN RADIAT ONCOL, V25, P260, DOI 10.1016/j.semradonc.2015.05.004; Keith B, 2012, NAT REV CANCER, V12, P9, DOI 10.1038/nrc3183; Komatsu M, 2010, FEBS LETT, V584, P1374, DOI 10.1016/j.febslet.2010.02.017; Laderoute KR, 2006, MOL CELL BIOL, V26, P5336, DOI 10.1128/MCB.00166-06; Laderoute KR, 2002, MOL CELL BIOL, V22, P2515, DOI 10.1128/MCB.22.8.2515-2523.2002; McKeown SR, 2014, BRIT J RADIOL, V87, DOI 10.1259/bjr.20130676; Murai M, 2005, CLIN CANCER RES, V11, P1021; Ney PA, 2015, BBA-MOL CELL RES, V1853, P2775, DOI 10.1016/j.bbamcr.2015.02.022; Puissant A, 2012, AM J CANCER RES, V2, P397; Rouschop KMA, 2010, J CLIN INVEST, V120, P127, DOI 10.1172/JCI40027; Simpson J., 2008, SURGERY, V26, P329, DOI DOI 10.1016/J.CANRAD.2010.06.017; Tam SY, 2017, RADIAT ONCOL, V12, DOI 10.1186/s13014-017-0795-y; Tanida I, 2004, INT J BIOCHEM CELL B, V36, P2503, DOI 10.1016/j.biocel.2004.05.009; Wouters A, 2007, ONCOLOGIST, V12, P690, DOI 10.1634/theoncologist.12-6-690; Zadra G, 2015, MOL CANCER RES, V13, P1059, DOI 10.1158/1541-7786.MCR-15-0068; Zhao J, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2014.565; Zhou YY, 2015, BIOSCIENCE REP, V35, DOI 10.1042/BSR20140141	25	5	5	0	1	ACADEMIC PRESS INC ELSEVIER SCIENCE	SAN DIEGO	525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA	0006-291X	1090-2104		BIOCHEM BIOPH RES CO	Biochem. Biophys. Res. Commun.	SEP 17	2019	517	2					193	200		10.1016/j.bbrc.2019.07.043			8	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	KB2YR	WOS:000506366800003	31331640	hybrid, Green Published			2022-04-25	
J	Ghasemi, T; Khalaj-Kondori, M; Feizi, MAH; Asadi, P				Ghasemi, Tayyebeh; Khalaj-Kondori, Mohammad; feizi, Mohammad Ali Hosseinpour; Asadi, Parviz			lncRNA-miRNA-mRNA interaction network for colorectal cancer; An in silico analysis	COMPUTATIONAL BIOLOGY AND CHEMISTRY			English	Article						lncRNA; Colorectal cancer; Microarray; lncRNA-miRNA-mRNA network	LONG NONCODING RNAS; EXPRESSION; FOXP2; INVASION; GENE; IDENTIFICATION; BIOMARKERS; SIGNATURE; CARCINOMA; AUTOPHAGY	Background: Colorectal cancer (CRC) is one of the most frequent and diagnosed diseases. Accumulating evidences showed that mRNAs and noncoding RNAs play important regulatory roles in tumorigenesis. Identification and determining the relationship between them can help diagnosis and treatment of cancer. Methods: Here we analyzed three micmarray datasets; GSE110715, GSE32323 and GSE21510, to identify differentially expressed lncRNAs and mRNAs in CRC. The adjusted p-value <= 0.05 was considered statistically significant. Gene set enrichment analysis was carried out using DAVID tool. The miRCancer database was searched to obtain differentially expressed miRNAs in colorectal cancer, and the miRDB database was used to attain the targets of the obtained miRNAs. To predict the 1ncRNA-miRNA interactions we used DIANA-LncBase v2 and RegRNA 2.0. Finally the lncRNA-miRNA-mRNA-signaling pathway network was constructed using Cytoscape v3.1. Results: By analyzing the three datasets, a total of 21 mRNAs (15 up- and 6 down-regulated) and 24 lncRNAs (18 up- and 6 down-regulated) were identified as common differentially expressed genes between CRC tumor and marginal tissues. Nevertheless, the constructed 1ncRNA-miRNA-mRNA-signaling pathway network revealed a convergence on 6 lncRNAs (3 up- and 3 downregulated), 7 mRNAs (2 up- and 5 downregulated) and 6 miRNAs (3 up- and 3 downregulated). We found that dysregulation of lncRNAs such as PCBP1-AS1, UCA1 and SNHG16 could sequester several miRNAs such as hsa-miR-582-5p and hsa-miR-198 and promote the proliferation, invasion and drug resistance of colorectal cancer cells. Conclusions: We introduced a set of lncRNAs, mRNAs and miRNAs differentially expressed in CRC which might be considered for further experimental research as potential biomarkers of CRC development.	[Ghasemi, Tayyebeh; Khalaj-Kondori, Mohammad; feizi, Mohammad Ali Hosseinpour] Univ Tabriz, Fac Nat Sci, Dept Anim Biol, Tabriz, Iran; [Asadi, Parviz] Shahid Mahallati Hosp, Gastroenterol Ward, Tabriz, Iran		Khalaj-Kondori, M (corresponding author), Univ Tabriz, Fac Nat Sci, Dept Anim Biol, Tabriz, Iran.	khalaj@tabrizu.ac.ir		Hosseinpour Feizi, Mohammad Ali/0000-0002-1508-5022			Allemani C, 2013, BMJ OPEN, V3, DOI 10.1136/bmjopen-2013-003055; Amit I, 2009, SCIENCE, V326, P257, DOI 10.1126/science.1179050; Baldassarre A, 2012, INT J MOL SCI, V13, P16708, DOI 10.3390/ijms131216708; Barbagallo C, 2018, MOL THER-NUCL ACIDS, V12, P229, DOI 10.1016/j.omtn.2018.05.009; Cai J, 2019, J CANCER, V10, P611, DOI 10.7150/jca.28780; Chen, 2019, MOL CANCER, V18, P1, DOI DOI 10.1186/S12943-019-1014-2; Costa FF, 2010, BIOESSAYS, V32, P599, DOI 10.1002/bies.200900112; Cuiffo BG, 2014, CELL STEM CELL, V15, P762, DOI 10.1016/j.stem.2014.10.001; Dai MH, 2005, NUCLEIC ACIDS RES, V33, DOI 10.1093/nar/gni179; 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Biol. Chem.	DEC	2020	89								107370	10.1016/j.compbiolchem.2020.107370			9	Biology; Computer Science, Interdisciplinary Applications	Science Citation Index Expanded (SCI-EXPANDED)	Life Sciences & Biomedicine - Other Topics; Computer Science	PH6UK	WOS:000600544900004	32932199				2022-04-25	
J	Liu, JX; Cai, JP; Fan, P; Zhang, NS; Cao, YG				Liu, Jiuxi; Cai, Jiapei; Fan, Peng; Zhang, Naisheng; Cao, Yongguo			The Abilities of Salidroside on Ameliorating Inflammation, Skewing the Imbalanced Nucleotide Oligomerization Domain-Like Receptor Family Pyrin Domain Containing 3/Autophagy, and Maintaining Intestinal Barrier Are Profitable in Colitis	FRONTIERS IN PHARMACOLOGY			English	Article						salidroside; colitis; NLRP3 inflammasome; autophagy; intestinal barrier; inflammation	SODIUM-INDUCED COLITIS; ULCERATIVE-COLITIS; INHIBITION; ACTIVATION; AUTOPHAGY; DISEASE; PROTEIN; INJURY; MICE	Salidroside (Sal), as a major glycoside extracted from Rhodiola rosea L., has exhibited its mighty anti-aging, anti-oxidant, anti-cancer, anti-inflammation, and neuroprotective effects in many diseases. Recently, it has showed its protective effect in colitis mice by activating the SIRT1/FoxOs pathway. Whereas, it is not known whether Sal has other protective mechanisms on dextran sulfate sodium (DSS)-induced colitis in mice. In this study, we investigated the protective effects and mechanisms of Sal on DSS-induced colitis in mice. The results demonstrated Sal was a competent candidate in the treatment of ulcerative colitis (UC). Sal remitted DSS-induced disease activity index (DAI), colon length shortening, and colonic pathological damage. Simultaneously, Sal alleviated excessive inflammation by reversing the IL-1 beta, TNF-alpha, and IL-10 protein levels in DSS-treated mice. Western blot analysis revealed that Sal inhibited p65 and p38 activation together with peroxisome proliferator-activated receptor (PPAR gamma) up-regulation. In addition, Sal skewed the imbalanced activation of nucleotide oligomerization domain-like receptor family pyrin domain containing 3 inflammasome and autophagy contributing to colitis recovery. The damaged intestinal barrier induced by DSS was also alleviated along with plasma lipopolysaccharides (LPS) reduction after Sal treatment. In vitro, Sal showed PPAR gamma-dependent anti-inflammatory effect in LPS-stimulated RAW264.7 cells. In summary, our results demonstrated that Sal might be an effective factor for UC treatment and its pharmacological value deserved further development.	[Liu, Jiuxi; Cai, Jiapei; Fan, Peng; Zhang, Naisheng; Cao, Yongguo] Jilin Univ, Coll Vet Med, Dept Clin Vet Med, Changchun, Jilin, Peoples R China		Zhang, NS; Cao, YG (corresponding author), Jilin Univ, Coll Vet Med, Dept Clin Vet Med, Changchun, Jilin, Peoples R China.	zhangns@jlu.edu.cn; ygcao82@jlu.edu.cn			Key Project of Chinese National Programs for Research and Development [2016YFD0501009]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31572582, 31472248]	This work was supported by the Key Project of Chinese National Programs for Research and Development (no. 2016YFD0501009) and National Natural Science Foundation of China (nos. 31572582 and 31472248).	Almeer RS, 2018, FOOD CHEM TOXICOL, V115, P49, DOI 10.1016/j.fct.2018.03.002; Cao HY, 2018, J AGR FOOD CHEM, V66, P13133, DOI 10.1021/acs.jafc.8b03942; Chen X, 2009, MOL CELL BIOCHEM, V332, P85, DOI 10.1007/s11010-009-0177-3; Chung HY, 2011, J DENT RES, V90, P830, DOI 10.1177/0022034510387794; Cosin-Roger J, 2017, NAT COMMUN, V8, DOI 10.1038/s41467-017-00213-3; Di AK, 2018, IMMUNITY, V49, P56, DOI 10.1016/j.immuni.2018.04.032; Fan XJ, 2016, ONCOL REP, V36, P3559, DOI 10.3892/or.2016.5138; Gao J, 2016, METAB BRAIN DIS, V31, P771, DOI 10.1007/s11011-016-9813-2; Gupta RA, 2015, J ETHNOPHARMACOL, V164, P239, DOI 10.1016/j.jep.2015.01.039; Gurung P, 2015, SCI REP-UK, V5, DOI 10.1038/srep14488; Hampe J, 2007, NAT GENET, V39, P207, DOI 10.1038/ng1954; Hausmann M, 2007, CLIN EXP IMMUNOL, V148, P373, DOI 10.1111/j.1365-2249.2007.03350.x; Jang YJ, 2019, GUT MICROBES, V10, P696, DOI 10.1080/19490976.2019.1589281; Kaplan GG, 2015, NAT REV GASTRO HEPAT, V12, P720, DOI 10.1038/nrgastro.2015.150; Kaser A, 2011, GASTROENTEROLOGY, V140, P1738, DOI 10.1053/j.gastro.2011.02.048; Kelly CR, 2019, JAMA-J AM MED ASSOC, V321, P151, DOI 10.1001/jama.2018.20397; Kiernan MG, 2020, J CROHNS COLITIS, V14, P118, DOI 10.1093/ecco-jcc/jjz117; Kihara N, 2003, GUT, V52, P713, DOI 10.1136/gut.52.5.713; Kim KN, 2010, EUR J PHARMACOL, V649, P369, DOI 10.1016/j.ejphar.2010.09.032; Kim KA, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0047713; Nakanishi Y, 2015, MUCOSAL IMMUNOL, V8, P152, DOI 10.1038/mi.2014.53; Neurath MF, 2014, NAT REV IMMUNOL, V14, P329, DOI 10.1038/nri3661; Ordas I, 2012, LANCET, V380, P1606, DOI 10.1016/S0140-6736(12)60150-0; Park EJ, 2010, J PEDIATR GASTR NUTR, V50, P321, DOI 10.1097/MPG.0b013e3181ae2ba0; Pekow J, 2017, CLIN CANCER RES, V23, P5281, DOI 10.1158/1078-0432.CCR-17-0171; Rahimian R, 2016, IMMUNOPHARM IMMUNOT, V38, P432, DOI 10.1080/08923973.2016.1231202; Retnakumar SV, 2019, TRENDS MOL MED, V25, P516, DOI 10.1016/j.molmed.2019.03.002; Shen P, 2019, BIOMED PHARMACOTHER, V110, P786, DOI 10.1016/j.biopha.2018.12.033; Sun Q, 2017, MOL MED, V23, P188, DOI 10.2119/molmed.2017.00077; Toma C, 2011, CELL MICROBIOL, V13, P1783, DOI 10.1111/j.1462-5822.2011.01660.x; Trivedi PP, 2013, DIGEST DIS SCI, V58, P3460, DOI 10.1007/s10620-013-2831-6; Ungaro R, 2017, LANCET, V389, P1756, DOI 10.1016/S0140-6736(16)32126-2; van der Post S, 2019, GUT, V68, P2142, DOI 10.1136/gutjnl-2018-317571; Wang Y, 2017, CELL PHYSIOL BIOCHEM, V42, P34, DOI 10.1159/000477112; Yadav PN, 2003, J PHARMACOL EXP THER, V305, P925, DOI 10.1124/jpet.103.049171; Zhang J, 2014, MUCOSAL IMMUNOL, V7, P1139, DOI 10.1038/mi.2014.1; Zhang ZC, 2017, INT IMMUNOPHARMACOL, V49, P168, DOI 10.1016/j.intimp.2017.05.033; Zhang ZC, 2017, FRONT IMMUNOL, V8, DOI 10.3389/fimmu.2017.00558; Zhu Y, 2011, DNA CELL BIOL, V30, P809, DOI 10.1089/dna.2010.1183; Zigmond E, 2014, IMMUNITY, V40, P720, DOI 10.1016/j.immuni.2014.03.012	40	8	9	5	15	FRONTIERS MEDIA SA	LAUSANNE	AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND	1663-9812			FRONT PHARMACOL	Front. Pharmacol.	DEC 2	2019	10								1385	10.3389/fphar.2019.01385			11	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	JW0JR	WOS:000502746200001	31849652	Green Published, gold			2022-04-25	
J	Elshafay, A; Tinh, NX; Salman, S; Shaheen, YS; Othman, EB; Elhady, MT; Kansakar, AR; Tran, L; Van, L; Hirayama, K; Huy, NT				Elshafay, Abdelrahman; Ngo Xuan Tinh; Salman, Samar; Shaheen, Yara Saber; Othman, Eman Bashir; Elhady, Mohamed Tamer; Kansakar, Aswin Ratna; Linh Tran; Le Van; Hirayama, Kenji; Nguyen Tien Huy			Ginsenoside Rk1 bioactivity: a systematic review	PEERJ			English	Review						Ginsenoside; Systematic review; Rk1; Clinical pharmacology	PANAX-GINSENG; LUNG-CANCER; INHIBITION; APOPTOSIS; GLYCOSIDES; INDUCTION; RESPONSES; SAPONINS; EXTRACTS; RG5RK1	Ginsenoside Rk1 (G-Rk1) is a unique component created by processing the ginseng Plant (mainly Sung Ginseng (SG)) at high temperatures. The aim of our study was to systematically review the pharmacological effects G-Rk1. We utilized and manually searched eight data bases to select in vivo and invitro original studies that provided information about biological, pharmaceutical effects of G-Rk1 and were published up to July 2017 with no restriction on language or study design. Out of the 156 papers identified, we retrieved 28 eligible papers in the first skimming phase of research. Several articles largely described the G-Rk1 anti-cancer activity investigating "cell viability","cell proliferation inhibition", "apoptotic activity", and "effects of G-Rk1 on G1 phase and autophagy in tumor cells" either alone or in combination with G-Rg5. Others proved that it has antiplatelet aggregation activities, anti-inflammatory effects, anti-insulin resistance, nephroprotective effect, antimicrobial effect, cognitive function enhancement, lipid accumulation reduction and prevents osteoporosis. In conclusion, G-Rk1 has a significant anti-tumor effect on liver cancer, melanoma, lung cancer, cervical cancer, colon cancer, pancreatic cancer, gastric cancer, and breast adenocarcinoma against in vitro cell lines. In vivo experiments are further warranted to confirm these effects.	[Elshafay, Abdelrahman] Al Azhar Univ, Fac Med, Cairo, Egypt; [Ngo Xuan Tinh; Le Van] Univ Med & Pharm, Fac Pharm, Ho Chi Minh, Vietnam; [Salman, Samar] Tanta Univ Hosp, Tanta, Egypt; [Shaheen, Yara Saber] Cairo Univ, Fac Med, Cairo, Egypt; [Othman, Eman Bashir] Tripoli Cent Hosp, Dept Med, Tripoli, Libya; [Elhady, Mohamed Tamer] Zagazig Univ, Dept Pediat, Sharkia, Egypt; [Kansakar, Aswin Ratna] Dirghayu Guru Hosp, Kathmandu, Nepal; [Kansakar, Aswin Ratna] Res Ctr, Kathmandu, Nepal; [Linh Tran] Duy Tan Univ, Int Res & Dev, Da Nang, Vietnam; [Hirayama, Kenji] Nagasaki Univ, Dept Immunogenet, Inst Trop Med NEKKEN, Grad Sch Biomed Sci, Nagasaki, Japan; [Nguyen Tien Huy] Ton Duc Thang Univ, Evidence Based Med Res Grp, Ho Chi Minh City, Vietnam; [Nguyen Tien Huy] Ton Duc Thang Univ, Fac Appl Sci, Ho Chi Minh City, Vietnam; [Nguyen Tien Huy] Nagasaki Univ, Dept Clin Prod Dev, Inst Trop Med NEKKEN, Leading Grad Sch Program, Nagasaki, Japan; [Nguyen Tien Huy] Nagasaki Univ, Grad Sch Biomed Sci, Nagasaki, Japan		Huy, NT (corresponding author), Ton Duc Thang Univ, Evidence Based Med Res Grp, Ho Chi Minh City, Vietnam.; Huy, NT (corresponding author), Ton Duc Thang Univ, Fac Appl Sci, Ho Chi Minh City, Vietnam.; Huy, NT (corresponding author), Nagasaki Univ, Dept Clin Prod Dev, Inst Trop Med NEKKEN, Leading Grad Sch Program, Nagasaki, Japan.; Huy, NT (corresponding author), Nagasaki Univ, Grad Sch Biomed Sci, Nagasaki, Japan.	nguyentienhuy@tdt.edu.vn	Tran, Linh/O-6874-2018; Huy, Nguyen Tien/B-2573-2010; Hirayama, Kenji/AAN-7065-2021	Tran, Linh/0000-0001-8667-082X; Huy, Nguyen Tien/0000-0002-9543-9440; Kansakar, Aswin Ratna/0000-0003-4410-8964; Tamer Ibrahem, Mohamed/0000-0003-1339-1138	Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [16H05844]; Japan Initiative for Global Research Network on Infectious Diseases (J-GRID)Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)	This study was supported in part by a "Grant-in-Aid for Scientific Research (B)" (16H05844, 2016-2019 for Nguyen Tien Huy) from Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan and by the Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) for Kenji Hirayama. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.	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J	Chan, CK; Tong, KL; Wong, PF; Kadir, H				Chan, Chim-Kei; Tong, Kind-Leng; Wong, Pooi-Fong; Kadir, Habsah			Deoxyelephantopin induces ROS-mediated autophagy and apoptosis in human colorectal cancer in vitro and in vivo	ASIAN PACIFIC JOURNAL OF TROPICAL BIOMEDICINE			English	Article						Deoxyelephantopin; Autophagy; PI3K; mTOR; Colorectal cancer; MAPK	ELEPHANTOPUS-SCABER; SIGNALING PATHWAY; CELLS; ACTIVATION; GROWTH; MTOR; P38	Objective: To systematically map the stepwise events leading to deoxyelephantopin-induced cell death of HCT116 human colorectal cancer cells and evaluate the effectiveness of deoxyelephantopin in vivo. Methods: HCT116 cells were treated with deoxyelephantopin at various concentrations and time points. Autophagy was confirmed by the detection of autophagosomes and autophagosomal proteins by electron microscopy and Western blotting assays, respectively, and then validated by siRNA knockdown. In addition, apoptosis was confirmed by the detection of apoptosis-related proteins. The intracellular reactive oxygen species (ROS) level was measured using flow cytometry. The growth inhibitory effect of deoxyelephantopin was further evaluated in vivo using a mouse xenograft model. Results: Deoxyelephantopin firstly elevated ROS production, which then triggered autophagic flux with the accumulation of autophagosomal proteins including LC3A/B, ATG5, and ATG7, followed by the induction of apoptosis via the intrinsic and extrinsic pathways. Pre-treatment with N-acetyl-L-cysteine, a ROS inhibitor, reversed both apoptosis and autophagy. The knockdown of LC3 prevented apoptosis induction which confirmed that deoxyelephantopin induced autophagy-dependent apoptosis in HCT116 cells. Accumulation of ROS also activated apoptosis via the mitogen-activated protein kinases signaling pathway. Furthermore, deoxyelephantopin also inhibited the PI3K/AKT/mTOR pathway, which then released the inhibition of autophagy. In vivo study further showed that deoxyelephantopin significantly suppressed the growth of HCT116 subcutaneous xenograft in nude mice. Conclusions: Our findings revealed that deoxyelephantopin elevates oxidative stress and induces ROS-dependent autophagy followed by apoptosis in HCT116 cells via the concerted modulation of multiple signaling pathways. These findings further support the development of deoxyelephantopin as a therapeutic agent for colorectal cancer.	[Chan, Chim-Kei; Kadir, Habsah] Univ Malaya, Fac Sci, Inst Biol Sci, Biomol Res Grp,Biochem Program, Kuala Lumpur 50603, Malaysia; [Tong, Kind-Leng; Wong, Pooi-Fong] Univ Malaya, Fac Med, Dept Pharmacol, Kuala Lumpur 50603, Malaysia		Kadir, H (corresponding author), Univ Malaya, Fac Sci, Inst Biol Sci, Biomol Res Grp,Biochem Program, Kuala Lumpur 50603, Malaysia.; Wong, PF (corresponding author), Univ Malaya, Fac Med, Dept Pharmacol, Kuala Lumpur 50603, Malaysia.	wongpf@um.edu.my; drhabsah55@gmail.com	WONG, POOI-FONG PF/B-5234-2010	WONG, POOI-FONG PF/0000-0002-6705-2521			Bacus SS, 2001, ONCOGENE, V20, P147, DOI 10.1038/sj.onc.1204062; Balachandran P, 2005, PHARMACOL RES, V51, P19, DOI 10.1016/j.phrs.2004.04.010; Chan CK, 2016, MOLECULES, V21, DOI 10.3390/molecules21030385; Chan CK, 2015, J ETHNOPHARMACOL, V168, P291, DOI 10.1016/j.jep.2015.03.072; Cory S, 2002, NAT REV CANCER, V2, P647, DOI 10.1038/nrc883; Cragg GM, 2005, J ETHNOPHARMACOL, V100, P72, DOI 10.1016/j.jep.2005.05.011; Deng Q, 2013, CELL DEATH DIS, V4, DOI 10.1038/cddis.2013.324; Deveraux QL, 1999, EMBO J, V18, P5242, DOI 10.1093/emboj/18.19.5242; Dhillon AS, 2007, ONCOGENE, V26, P3279, DOI 10.1038/sj.onc.1210421; Dutta D, 2016, BMC CANCER, V16, DOI 10.1186/s12885-016-2055-1; Farha AK, 2015, NAT PROD RES, V29, P2341, DOI 10.1080/14786419.2015.1012165; Farha AK, 2014, CELL BIOL TOXICOL, V30, P331, DOI 10.1007/s10565-014-9288-z; Fulda S, 2006, ONCOGENE, V25, P4798, DOI 10.1038/sj.onc.1209608; Fulda S, 2015, ONCOGENE, V34, P5105, DOI 10.1038/onc.2014.458; Guertin DA, 2007, CANCER CELL, V12, P9, DOI 10.1016/j.ccr.2007.05.008; Guzinska-Ustymowicz K, 2009, ANTICANCER RES, V29, P3049; Ho WY, 2009, J MED PLANTS RES, V3, P1212; Hosokawa N, 2009, MOL BIOL CELL, V20, P1981, DOI 10.1091/mbc.E08-12-1248; Hsieh MJ, 2014, PHYTOMEDICINE, V21, P1746, DOI 10.1016/j.phymed.2014.07.013; Huang CC, 2010, BRIT J PHARMACOL, V159, P856, DOI 10.1111/j.1476-5381.2009.00581.x; Huang J, 2008, BIOCHEM J, V412, P179, DOI 10.1042/BJ20080281; Kabeer FA, 2013, J INTEGR MED-JIM, V11, P269, DOI 10.3736/jintegrmed2013040; Kabeer FA, 2017, INTEGR MED RES, V6, P190, DOI 10.1016/j.imr.2017.03.004; Kim S, 2008, J CELL BIOCHEM, V105, P971, DOI 10.1002/jcb.21905; Kischkel FC, 2001, J BIOL CHEM, V276, P46639, DOI 10.1074/jbc.M105102200; Kumar D, 2014, CANCER LETT, V343, P179, DOI 10.1016/j.canlet.2013.10.003; Li X, 2013, ACTA PHARMACOL SIN, V34, P612, DOI 10.1038/aps.2013.23; Mehmood T, 2017, MOLECULES, V22, DOI 10.3390/molecules22061013; Mehmood T, 2017, BIOFACTORS, V43, P63, DOI 10.1002/biof.1324; Porta C, 2014, FRONT ONCOL, V4, DOI 10.3389/fonc.2014.00064; Qian HR, 2017, ONCOTARGET, V8, P62759, DOI 10.18632/oncotarget.18663; Sato T, 2008, METHOD ENZYMOL, V438, P307, DOI 10.1016/S0076-6879(07)38021-X; Shiau JY, 2017, ONCOTARGET, V8, P56942, DOI 10.18632/oncotarget.18183; Siegel RL, 2016, CA-CANCER J CLIN, V66, P7, DOI 10.3322/caac.21332; Singh S. D. J., 2005, Indian Journal of Pharmacology, V37, P238; Su CC, 2006, ANTICANCER RES, V26, P4379; Su MX, 2011, BIOCHEM BIOPH RES CO, V411, P342, DOI 10.1016/j.bbrc.2011.06.144; Unnati S, 2013, CHIN J NAT MEDICINES, V11, P16, DOI 10.3724/SP.J.1009.2013.00016; Vanneman M, 2012, NAT REV CANCER, V12, P237, DOI 10.1038/nrc3237; Wang QW, 2011, CANCER LETT, V302, P29, DOI 10.1016/j.canlet.2010.12.007; Wang YX, 2015, TOXINS, V7, P3030, DOI 10.3390/toxins7083030; Workman P, 2010, BRIT J CANCER, V102, P1555, DOI 10.1038/sj.bjc.6605642; Zhang R, 2008, APOPTOSIS, V13, P1465, DOI 10.1007/s10495-008-0278-6; Zhou YY, 2015, BIOSCIENCE REP, V35, DOI 10.1042/BSR20140141; Zou JL, 2017, CELL PHYSIOL BIOCHEM, V42, P1812, DOI 10.1159/000479537	45	1	1	2	2	WOLTERS KLUWER MEDKNOW PUBLICATIONS	MUMBAI	WOLTERS KLUWER INDIA PVT LTD , A-202, 2ND FLR, QUBE, C T S  NO 1498A-2 VILLAGE MAROL, ANDHERI EAST, MUMBAI, 400059, INDIA	2221-1691	2588-9222		ASIAN PAC J TROP BIO	Asian Pac. Trop. Biomed.	MAR	2020	10	3					120	135		10.4103/2221-1691.276318			16	Tropical Medicine	Science Citation Index Expanded (SCI-EXPANDED)	Tropical Medicine	KM9EU	WOS:000514445200004		gold			2022-04-25	
J	Acharya, B; Chaijaroenkul, W; Na-Bangchang, K				Acharya, Bishwanath; Chaijaroenkul, Wanna; Na-Bangchang, Kesara			Atractylodin inhibited the migration and induced autophagy in cholangiocarcinoma cells via PI3K/AKT/mTOR and p38MAPK signalling pathways	JOURNAL OF PHARMACY AND PHARMACOLOGY			English	Article						atractylodin; autophagy; cholangiocarcinoma; PI3K/AKT/mTOR; p38MAPK	COLON-CANCER; CYCLE ARREST; APOPTOSIS; SUPPRESSES; INVASION	Objectives The effects of atractylodin (ATD), the bioactive compound from Atractylodes lancea, on migration and autophagy status of cholangiocarcinoma cell line were investigated. Methods Cytotoxic activity and effects on cell migration and invasion were evaluated by MTT and trans-well assay, respectively. Autophagy and underlying molecular mechanisms were investigated using flow cytometry and western blot analysis. Key findings ATD regulated the activity of PI3K/AKT/mTOR and p38MAPK signalling pathways which contributed to autophagy induction. HuCCT-1 cell growth was inhibited by ATD in a time- and dose-dependent manner. ATD inhibited the migration and invasion of HuCCT1 cells in a concentration-dependent manner. It also induced autophagy in HuCCT1 cells in a time- and dose-dependent manner. The SB202190 (autophagy inducer) and 3-MA (autophagy inhibitor) significantly increased and decreased the rate of ATD-induced autophagy, respectively. The 24 h exposure of ATD inhibited the phosphorylation of phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (p38MAPK) and increased Beclin-1 expression and LC3 conversion. It also reduced p-AKT/AKT, p-mTOR/mTOR and p-p38MAPK/p38MAPK. Conclusions ATD inhibits the proliferation and induces CCA cell autophagy via regulating PI3K/AKT/mTOR and p38MAPK signalling pathways.	[Acharya, Bishwanath; Chaijaroenkul, Wanna; Na-Bangchang, Kesara] Thammasat Univ, Chulabhorn Int Coll Med, Rangsit Ctr, Klongluang, Pathum Thani, Thailand; [Na-Bangchang, Kesara] Thammasat Univ, Chulabhorn Int Coll Med, Ctr Excellence Pharmacol & Mol Biol Malaria & Cho, Rangsit Ctr, Klongluang 12120, Pathum Thani, Thailand; [Na-Bangchang, Kesara] Thammasat Univ, Drug Discovery & Dev Ctr, Rangsit Ctr, Klongluang, Pathum Thani, Thailand		Na-Bangchang, K (corresponding author), Thammasat Univ, Chulabhorn Int Coll Med, Ctr Excellence Pharmacol & Mol Biol Malaria & Cho, Rangsit Ctr, Klongluang 12120, Pathum Thani, Thailand.	kesaratmu@yahoo.com		Acharya, Bishwanath/0000-0001-8603-0574	Thammasat University (Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma), Chulabhorn International College of Medicine at Thammasat University, Rangsit Center, Thailand; National Research Council of Thailand (Ministry of Higher Education, Science, Research, and Innovation) [2020-01]	This study was supported by Thammasat University (Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma), Chulabhorn International College of Medicine at Thammasat University, Rangsit Center, Thailand. K.N.-B. is supported by the National Research Council of Thailand (Ministry of Higher Education, Science, Research, and Innovation) under the Research Team Promotion grant [grant number 2020-01].	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Pharm. Pharmacol.	SEP	2021	73	9					1191	1200		10.1093/jpp/rgab036		APR 2021	10	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	UQ1GR	WOS:000695820100006	33885818				2022-04-25	
J	Lai, K; Matthews, S; Wilmott, JS; Killingsworth, MC; Yong, JL; Caixeiro, NJ; Wykes, J; Samakeh, A; Forstner, D; Lee, M; McGuinness, J; Niles, N; Hong, A; Ebrahimi, A; Lee, CS				Lai, Kenneth; Matthews, Slade; Wilmott, James S.; Killingsworth, Murray C.; Yong, Jim L.; Caixeiro, Nicole J.; Wykes, James; Samakeh, Allan; Forstner, Dion; Lee, Mark; McGuinness, John; Niles, Navin; Hong, Angela; Ebrahimi, Ardalan; Lee, Cheok Soon			Differences in LC3B expression and prognostic implications in oropharyngeal and oral cavity squamous cell carcinoma patients	BMC CANCER			English	Article						Autophagy; LC3B; Oropharyngeal; Oral cavity; SCC; HPV; Immunohistochemistry; Survival outcome	BREAST-CANCER CELLS; HUMAN-PAPILLOMAVIRUS; AUTOPHAGY INHIBITION; COLORECTAL-CANCER; RADIATION-THERAPY; INCIDENCE RATES; POOR-PROGNOSIS; COLON-CANCER; RISK-FACTORS; SURVIVAL	Background: This study examined the prognostic significance of microtubule-associated protein light chain 3B (LC3B) expression in oropharyngeal and oral cavity squamous cell carcinoma (SCC). The prognostic significance of LC3B expression in relation to human papillomavirus (HPV) status in oropharyngeal SCC was also examined. Methods: Tissue microarrays (TMAs) were constructed from formalin-fixed, paraffin-embedded oropharyngeal (n =47) and oral cavity (n = 95) SCC tissue blocks from patients with long-term recurrence and overall survival data (median =47 months). LC3B expression on tumour was assessed by immunohistochemistry and evaluated for associations with clinicopathological variables. LC3B expression was stratified into high and low expression cohorts using ROC curves with Manhattan distance minimisation, followed by Kaplan-Meier and multivariable survival analyses. Interaction terms between HPV status and LC3B expression in oropharyngeal SCC patients were also examined by joint-effects and stratified analyses. Results: Kaplan-Meier survival and univariate analyses revealed that high LC3B expression was correlated with poor overall survival in oropharyngeal SCC patients (p = 0.007 and HR = 3.18, 95% CI 1.31 7.71, p = 0.01 respectively). High LC3B expression was also an independent prognostic factor for poor overall survival in oropharyngeal SCC patients (HR = 4.02, 95% CI 1.38 11.47, p = 0.011). In contrast, in oral cavity SCC, only disease-free survival remained statistically significant after univariate analysis (HR = 2.36, 95% CI 1.19 4.67, p = 0.014), although Kaplan-Meier survival analysis showed that high LC3B expression correlated with poor overall and disease-free survival (p = 0.046 and 0.011 respectively), Purthermore, oropharyngeal SCC patients with HPV-negative/high LC3B expression were correlated with poor overall survival in both joint-effects and stratified presentations (p = 0.024 and 0.032 respectively). Conclusions: High LC3B expression correlates with poor prognosis in oropharyngeal and oral cavity SCC, which highlights the importance of autophagy in these malignancies. High LC3B expression appears to be an independent prognostic marker for oropharyngeal SCC but not for oral cavity SCC patients. The difference in the prognostic significance of LC3B between oropharyngeal and oral cavity SCCs further supports the biological differences between these malignancies. The possibility that oropharyngeal SCC patients with negative HPV status and high LC3B expression were at particular risk of a poor outcome warrants further investigation in prospective studies with larger numbers.	[Lai, Kenneth; Matthews, Slade; Wilmott, James S.; Hong, Angela; Lee, Cheok Soon] Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia; [Lai, Kenneth; Killingsworth, Murray C.; Caixeiro, Nicole J.; Lee, Cheok Soon] Western Sydney Univ, Sch Med, Discipline Pathol, Sydney, NSW, Australia; [Lai, Kenneth; Killingsworth, Murray C.; Caixeiro, Nicole J.; Lee, Cheok Soon] Ingham Inst Appl Med Res, Ctr Oncol Educ & Res Translat CONCERT, Sydney, NSW, Australia; [Lai, Kenneth; Killingsworth, Murray C.; Yong, Jim L.; Lee, Cheok Soon] Liverpool Hosp, SSWPS, Dept Anat Pathol, Sydney, NSW, Australia; [Matthews, Slade] Univ Sydney, Bosch Inst, Sydney, NSW, Australia; [Wilmott, James S.] Melanoma Inst Australia, Sydney, NSW, Australia; [Killingsworth, Murray C.; Wykes, James; Forstner, Dion] Univ New South Wales, Fac Med, Sydney, NSW, Australia; [Wykes, James; Samakeh, Allan; McGuinness, John; Niles, Navin; Ebrahimi, Ardalan] Liverpool Hosp, Dept Head & Neck Surg, Sydney, NSW, Australia; [Forstner, Dion] Liverpool Hosp, Dept Radiat Oncol, Sydney, NSW, Australia; [Lai, Kenneth] Ingham Inst Appl Med Res, 1 Campbell St, Liverpool, NSW 2170, Australia		Lai, K (corresponding author), Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia.; Lai, K (corresponding author), Western Sydney Univ, Sch Med, Discipline Pathol, Sydney, NSW, Australia.; Lai, K (corresponding author), Ingham Inst Appl Med Res, Ctr Oncol Educ & Res Translat CONCERT, Sydney, NSW, Australia.; Lai, K (corresponding author), Liverpool Hosp, SSWPS, Dept Anat Pathol, Sydney, NSW, Australia.; Lai, K (corresponding author), Ingham Inst Appl Med Res, 1 Campbell St, Liverpool, NSW 2170, Australia.	k.lai@uws.edu.au	Wilmott, James/AGA-8227-2022; Killingsworth, Murray/O-3736-2019; Matthews, Slade/J-4939-2019	Wilmott, James/0000-0002-6750-5244; Killingsworth, Murray/0000-0002-6125-1183; Matthews, Slade/0000-0002-1652-543X; Forstner, dion/0000-0002-6963-6942	Centre for Oncology Education and Research Translation (CONCERT) - Cancer Institute of New South Wales, Australia	This design of the study and collection, analysis, interpretation of data and in writing the manuscript was supported by internal funds and the Centre for Oncology Education and Research Translation (CONCERT) is funded by the Cancer Institute of New South Wales, Australia.	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J	Karasic, TB; Rosen, MA; O'Dwyer, PJ				Karasic, Thomas B.; Rosen, Mark A.; O'Dwyer, Peter J.			Antiangiogenic tyrosine kinase inhibitors in colorectal cancer: is there a path to making them more effective?	CANCER CHEMOTHERAPY AND PHARMACOLOGY			English	Review						Sorafenib; Regorafenib; Antiangiogenesis; Colorectal cancer; VEGFR2 signaling; DCE-MRI	RENAL-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; PHASE-I TRIAL; ADVANCED SOLID TUMORS; OXALIPLATIN-BASED CHEMOTHERAPY; COMBINATION TARGETED THERAPY; FACTOR RECEPTOR INHIBITOR; REGORAFENIB BAY 73-4506; GLOBAL EVALUATION TRIAL; CONTRAST-ENHANCED MRI	Antiangiogenic therapy has a proven survival benefit in metastatic colorectal cancer. Inhibition of the VEGF pathway using a variety of extracellular antibody approaches has clear benefit in combination with chemotherapy, while intracellular blockade using tyrosine kinase inhibitors (TKIs) such as sorafenib and regorafenib has had more limited success. Pharmacodynamic modeling using modalities such as DCE-MRI indicates potent antiangiogenic effects of these TKIs, yet numerous combination therapies, primarily with chemotherapy, have failed to demonstrate an additive benefit. The sole comparative study of a single agent TKI against placebo showed a survival benefit of regorafenib in patients with advanced, refractory disease. Preclinical data demonstrate synergy between antiantiogenic TKIs and targeted interventions including autophagy inhibition, and together with a renewed effort to define markers of susceptibility, such combinations may be a way to improve the limited efficacy of this once-promising drug class.	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Pharmacol.	OCT	2017	80	4					661	671		10.1007/s00280-017-3389-3			11	Oncology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	FH9TS	WOS:000411555500001	28721456				2022-04-25	
J	Abdel-Aziz, AK; Shouman, S; El-Demerdash, E; Elgendy, M; Abdel-Naim, AB				Abdel-Aziz, Amal Kamal; Shouman, Samia; El-Demerdash, Ebtehal; Elgendy, Mohamed; Abdel-Naim, Ashraf B.			Chloroquine synergizes sunitinib cytotoxicity via modulating autophagic, apoptotic and angiogenic machineries	CHEMICO-BIOLOGICAL INTERACTIONS			English	Article						Sunitinib; Chloroquine; Autophagy; Apoptosis; Angiogenesis; Oxidative stress	BREAST-CANCER CELLS; NITRIC-OXIDE; MICROVESSEL DENSITY; BECLIN 1; INHIBITION; SURVIVIN; EXPRESSION; GROWTH; DEATH; DRUG	Tyrosine kinases play a pivotal role in oncogenesis. Although tyrosine kinase inhibitors as sunitinib malate are used in cancer therapy, emerging studies report compromised cytotoxicity when used as monotherapy and thus combinations with other anti-cancer agents is recommended. Chloroquine is a clinically available anti-malarial agent which has been shown to exhibit anti-cancer activity. In the current study, we questioned whether chloroquine can modulate sunitinib cytotoxicity. We found that chloroquine synergistically augmented sunitinib cytotoxicity on human breast (MCF-7 and T-47D), cervical (Hela), colorectal (Caco-2 and HCT116), hepatocellular (HepG2), laryngeal (HEp-2) and prostate (PC3) cancer cell lines as indicated by combination and concentration reduction indices. These results were also consistent with that of Ehrlich ascites carcinoma (EAC) Swiss albino mice models as confirmed by tumor volume, weight, histopathological examination and PCNA expression. Sunitinib induced autophagy via upregulating beclin-1 expression which was blocked by chloroquine as evidenced by accumulated SQTSM1/p62 level. Furthermore, chloroquine augmented sunitinib-induced apoptosis by decreasing survivin level and increasing caspase 3 activity. Chloroquine also enhanced the antiangiogenic capacity of sunitinib as indicated by decreased CD34 expression and peritoneal/skin angiogenesis. Sunitinib when combined with chloroquine also increased reactive nitrogen species production via increasing inducible nitric oxide synthase expression and nitric oxide level whilst reduced reactive oxygen species production by increasing GSH level, activities of glutathione peroxidase and catalase and reducing lipid peroxides compared to sunitinib-only treated group. Taken together, these findings suggest that chloroquine enhanced sunitinib cytotoxicity in a synergistic manner via inducing apoptosis while switching off autophagic and angiogenic machineries. Nevertheless, further studies are required to elucidate the efficacy and safety profile of such combination. (C) 2014 Elsevier Ireland Ltd. All rights reserved.	[Abdel-Aziz, Amal Kamal; El-Demerdash, Ebtehal; Abdel-Naim, Ashraf B.] Ain Shams Univ, Fac Pharm, Dept Pharmacol & Toxicol, Cairo, Egypt; [Abdel-Aziz, Amal Kamal; Elgendy, Mohamed] European Inst Oncol, Dept Expt Oncol, Milan, Italy; [Shouman, Samia] Cairo Univ, Natl Canc Inst, Dept Canc Biol, Cairo, Egypt		Abdel-Naim, AB (corresponding author), Ain Shams Univ, Fac Pharm, Dept Pharmacol & Toxicol, Cairo, Egypt.	abnaim@pharma.asu.edu.eg	Abdel-Aziz, Amal Kamal/AAB-9050-2019; Abdel-Naim, Ashraf B/J-3199-2012; Abdel-Aziz, Amal Kamal/AAA-1360-2021; El-Demerdash, Ebtehal/ABE-6729-2020; shouman, samia/F-5395-2018	Abdel-Aziz, Amal Kamal/0000-0003-1709-1183; Abdel-Naim, Ashraf B/0000-0002-0400-9075; shouman, samia/0000-0002-2883-8775			Achudume A. 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Interact.	JUN 25	2014	217						28	40		10.1016/j.cbi.2014.04.007			13	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology	AJ4ML	WOS:000337650400004	24751611				2022-04-25	
J	Sutradhar, M; Rajeshwari; Barman, TR; Fernandes, AR; Paradinha, F; Roma-Rodrigues, C; da Silva, MFCG; Pombeiro, AJL				Sutradhar, Manas; Rajeshwari; Barman, Tannistha Roy; Fernandes, Alexandra R.; Paradinha, Fabiana; Roma-Rodrigues, Catarina; da Silva, M. Fatima C. Guedes; Pombeiro, Armando J. L.			Mixed ligand aroylhydrazone and N-donor heterocyclic Lewis base Cu(II) complexes as potential antiproliferative agents	JOURNAL OF INORGANIC BIOCHEMISTRY			English	Article						Mixed ligand copper(II) complexes; Aroylhydrazone ligand; X-ray structure; Antiproliferative agent; Human tumor cell lines	MICROWAVE-ASSISTED OXIDATION; BREAST-CANCER CELLS; CATALYST PRECURSORS; COBALT COMPLEXES; ALCOHOLS; HYDRAZONE; CHELATORS; APOPTOSIS; CRYSTAL; COPPER	A series of four mixed ligand aroylhydrazone and N-donor heterocyclic Lewis base Cu(II) complexes [CuL(X)](2) [L refers to the dianionic form of (5-bromo-2-hydroxybenzylidene)-2-hydroxybenzohydrazide; X = pyrazine (Pz; 1), pyridine (Py; 2), imidazole (Imz; 3) and 3-pyridinecarbonitrile (3-PyCN; 4)] has been synthesized and characterized by elemental analysis, various spectroscopic techniques and X-ray crystallography (for 1, 2 and 4). The antiproliferative effect of complexes 1-4 was examined in 4 human tumor cell lines (ovarian carcinoma (A2780), colorectal carcinoma (HCT116), lung adenocarcinoma (A549) and breast adenocarcinoma (MCF7)) and in normal human primary Fibroblasts. Complex 4 exhibits a high cytotoxic activity against ovarian and colorectal carcinoma cells (A2780, HCT116 respectively), with IC50 much lower than those for normal primary fibroblasts. Complex 4 could induce cell death via apoptosis but not autophagy in colorectal carcinoma cells.	[Sutradhar, Manas; Rajeshwari; Barman, Tannistha Roy; Fernandes, Alexandra R.; da Silva, M. Fatima C. Guedes; Pombeiro, Armando J. L.] Univ Lisbon, Ctr Quim Estrut, Inst Super Tecn, Ave Rovisco Pais, P-1049001 Lisbon, Portugal; [Fernandes, Alexandra R.; Paradinha, Fabiana; Roma-Rodrigues, Catarina] Univ Nova Lisboa, UCIBIO, Dept Ciencias Vida, Fac Ciencias & Tecnol, Campus Caparica, P-2829516 Caparica, Portugal		Sutradhar, M (corresponding author), Univ Lisbon, Ctr Quim Estrut, Inst Super Tecn, Ave Rovisco Pais, P-1049001 Lisbon, Portugal.	manas@tecnico.ulisboa.pt; ma.fernandes@fct.unl.pt; fatima.guedes@tecnico.ulisboa.pt	Roma-Rodrigues, Catarina/AAT-5658-2021; da Silva, M. Fátima C Guedes/H-8274-2012; Fernandes, Alexandra R/C-7465-2011; Pombeiro, Armando JL/I-5945-2012; Roma-Rodrigues, Catarina/S-6144-2016; Paradinha, Fabiana/L-2307-2018; da Silva, Maria de Fatima Guedes/P-3458-2019; Sutradhar, Manas/M-4089-2013; Roy Barman, Tannistha/L-7444-2014	Roma-Rodrigues, Catarina/0000-0002-8676-6562; da Silva, M. Fátima C Guedes/0000-0003-4836-2409; Fernandes, Alexandra R/0000-0003-2054-4438; Pombeiro, Armando JL/0000-0001-8323-888X; Roma-Rodrigues, Catarina/0000-0002-8676-6562; Paradinha, Fabiana/0000-0001-8833-677X; da Silva, Maria de Fatima Guedes/0000-0003-4836-2409; Sutradhar, Manas/0000-0003-3349-9154; Roy Barman, Tannistha/0000-0002-5147-7648	Foundation for Science and Technology (FCT), PortugalPortuguese Foundation for Science and Technology [PTDC/EQU-EQU/122025/2010, UID/QUI/00100/2013]; FCT, PortugalPortuguese Foundation for Science and TechnologyEuropean Commission [SFRH/BPD/86067/2012]; Unidade de Ciencias Biomoleculares Aplicadas - UCIBIO - FCT/MEC [UID/Multi/04378/2013]; ERDFEuropean Commission [POCI-01-0145-FEDER-007728]	Authors are grateful to the Foundation for Science and Technology (FCT) (projects PTDC/EQU-EQU/122025/2010 and UID/QUI/00100/2013), Portugal, for financial support. M.S. acknowledges the FCT, Portugal for a postdoctoral fellowship (SFRH/BPD/86067/2012). This work was also supported by the Unidade de Ciencias Biomoleculares Aplicadas - UCIBIO which is financed by national funds from FCT/MEC (UID/Multi/04378/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728). We are also thankful to the Portuguese NMR Network (IST-UL Centre) for access to the NMR facility.	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Inorg. Biochem.	OCT	2017	175						267	275		10.1016/j.jinorgbio.2017.07.034			9	Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	FI4DD	WOS:000411919000030	28806643				2022-04-25	
J	Kuo, YF; Su, YZ; Tseng, YH; Wang, SY; Wang, HM; Chueh, PJ				Kuo, Yu-Feng; Su, Ying-Zhen; Tseng, Yen-Hsueh; Wang, Sheng-Yang; Wang, Hsi-Ming; Chueh, Pin Ju			Flavokawain B, a novel chalcone from Alpinia pricei Hayata with potent apoptotic activity: Involvement of ROS and GADD153 upstream of mitochondria-dependent apoptosis in HCT116 cells	FREE RADICAL BIOLOGY AND MEDICINE			English	Article						Apoptosis; Alpinia pricei Hayata; Anticancer; Flavonoid; Flavokawain B; GADD153; ROS; Free radicals	ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; BLADDER-CANCER CELLS; CYCLE ARREST; MEDIATED APOPTOSIS; TRIGGERS APOPTOSIS; UP-REGULATION; COLON-CANCER; ER STRESS; P38 MAPK	Flavonoids synthesized from chalcone precursors in plants have been shown to possess cytotoxic activities with therapeutic potential. We have isolated the novel chalcone flavokawain B from Alpinia pricei Hayata, a plant native to Taiwan that is used in food and traditional Chinese medicine. Here, we report for the first time that flavokawain B significantly inhibits the growth of colon cancer cells and provide novel insight into the molecular mechanisms that underlie its apoptotic activity. Flavokawain B exerts its apoptotic action through ROS generation and GADD153 up-regulation, which lead to mitochondria-dependent apoptosis characterized by release of cytochrome c and translocation of Bak. The up-regulation of GADD153 in flavokawain B-treated HCT116 cells is associated with mitochondrial dysfunction and altered expression of Bcl-2 family members. Moreover, pretreatment with the ROS scavenger N-acetylcysteine abolishes flavokawain B-induced ROS generation, GADD153 up-regulation, and apoptosis. Similarly, RNAi-mediated gene silencing reduced flavokawain B-enhanced expression of GADD153 and apoptotic Bim, leading to diminished apoptosis. Interestingly, flavokawain B provokes G2/M accumulation as well as autophagy, in addition to apoptosis, suggesting that multiple pathways are activated in flavokawain B-mediated anticancer activity. Taken together, our data provide evidence for a molecular mechanism to explain the apoptotic activity of Alpinia plants, showing that flavokawain B acts through ROS generation and GADD153 up-regulation to regulate the expression of Bcl-2 family members, thereby inducing mitochondrial dysfunction and apoptosis in HCT116 cells. (C) 2010 Elsevier Inc. All rights reserved.	[Kuo, Yu-Feng; Su, Ying-Zhen; Wang, Hsi-Ming; Chueh, Pin Ju] Natl Chung Hsing Univ, Grad Inst Biomed Sci, Taichung 40227, Taiwan; [Tseng, Yen-Hsueh; Wang, Sheng-Yang] Natl Chung Hsing Univ, Dept Forestry, Taichung 40227, Taiwan		Chueh, PJ (corresponding author), Natl Chung Hsing Univ, Grad Inst Biomed Sci, Taichung 40227, Taiwan.	pjchueh@dragon.nchu.edu.tw	Wang, Sheng-Yang/M-9656-2019	Wang, Sheng-Yang/0000-0002-8579-3569; Chueh, Pin Ju/0000-0002-3200-7552	National Science CouncilMinistry of Science and Technology, Taiwan [NSC 97-2313-B-005-016-MY3]; Ministry of Education, Taiwan, Republic of ChinaMinistry of Education, Taiwan	We thank Dr. Tamotsu Yoshimori (Osaka University, Japan) for his generous gift of the pEGFP-LC3 construct, Dr. Ping-Shan Lai for his technical support with confocal microscopy, Dr. Chia-Che Chang for providing wild-type and p53-null HCT116 cells, Dr. Show-Mei Chuang for the HFW and A549 cells, and Jun-Hong Xiao for the preparation of flavokawain B. This work was supported by grants from the National Science Council (NSC 97-2313-B-005-016-MY3) and the Ministry of Education, Taiwan, Republic of China, under the ATU plan.	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Biol. Med.	JUL 15	2010	49	2					214	226		10.1016/j.freeradbiomed.2010.04.005			13	Biochemistry & Molecular Biology; Endocrinology & Metabolism	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Endocrinology & Metabolism	613XM	WOS:000279017800011	20398749				2022-04-25	
S	Liu, YY; Hill, RA; Li, YT		Norris, JS		Liu, Yong-Yu; Hill, Ronald A.; Li, Yu-Teh			Ceramide Glycosylation Catalyzed by Glucosylceramide Synthase and Cancer Drug Resistance	ROLE OF SPHINGOLIPIDS IN CANCER DEVELOPMENT AND THERAPY	Advances in Cancer Research		English	Review; Book Chapter							ADENOCARCINOMA CELL-LINE; TUMOR-NECROSIS-FACTOR; BREAST-CANCER; STEM-CELLS; MULTIDRUG-RESISTANCE; SPHINGOLIPID METABOLISM; MOLECULAR-CLONING; UDP-GALACTOSE; MUTANT P53; GLYCOSPHINGOLIPID SYNTHESIS	Glucosylceramide synthase (GCS), converting ceramide to glucosylceramide, catalyzes the first reaction of ceramide glycosylation in sphingolipid metabolism. This glycosylation by GCS is a critical step regulating the modulation of cellular activities by controlling ceramide and glycosphingolipids (GSLs). An increase of ceramide in response to stresses, such as chemotherapy, drives cells to proliferation arrest and apoptosis or autophagy; however, ceramide glycosylation promptly eliminates ceramide and consequently, these induced processes, thus protecting cancer cells. Further, persistently enhanced ceramide glycosylation can increase GSLs, participating in selecting cancer cells to drug resistance. GCS is overexpressed in diverse drug-resistant cancer cells and in tumors of breast, colon, and leukemia that display poor response to chemotherapy. As ceramide glycosylation by GCS is a rate-limiting step in GSL synthesis, inhibition of GCS sensitizes cancer cells to anticancer drugs and eradicates cancer stem cells. Mechanistic studies indicate that uncoupling ceramide glycosylation can modulate gene expression, decreasing MDR1 through the cSrc/beta-catenin pathway and restoring p53 expression via RNA splicing. These studies not only expand our knowledge in understanding how ceramide glycosylation affects cancer cells but also provide novel therapeutic approaches for targeting refractory tumors.	[Liu, Yong-Yu; Hill, Ronald A.] Univ Louisiana Monroe, Dept Basic Pharmaceut Sci, Monroe, LA 71209 USA; [Li, Yu-Teh] Tulane Univ, Sch Med, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA		Liu, YY (corresponding author), Univ Louisiana Monroe, Dept Basic Pharmaceut Sci, Monroe, LA 71209 USA.	yliu@ulm.edu	Liu, Yong-Yu/H-8593-2014	Liu, Yong-Yu/0000-0002-7968-0162	NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R15 CA167476] Funding Source: Medline; NCRR NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [5P20RR016456-11, P20 RR016456] Funding Source: Medline; NIGMS NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [P20 GM103424, 8 P20 GM103424-11] Funding Source: Medline; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R15CA167476] Funding Source: NIH RePORTER; 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J	Li, JN; Vangundy, Z; Poi, M				Li, Junan; Vangundy, Zachary; Poi, Ming			PTC209, a Specific Inhibitor of BMI1, Promotes Cell Cycle Arrest and Apoptosis in Cervical Cancer Cell Lines	ANTICANCER RESEARCH			English	Article						PTC209; BMI1; inhibition; cervical cancer; cancer stem cell	PROTEIN BMI-1; PTC-209; OVEREXPRESSION; PROLIFERATION; EPIDEMIOLOGY; AUTOPHAGY; MYELOMA	Background/Aim: Aberrant expression of the BMI1 oncogene has been prevalently found in a variety of human cancers, including cervical cancer. Recent studies have shown that PTC209, a specific BMI1 inhibitor, exhibits high potency in inhibiting the growth of colon, breast, oral cancer cells and cancer-initiating cells, indicative of its chemotherapeutic potential. In the current study, we evaluated the inhibitory abilities of PTC209 in cervical cancer cells. Materials and Methods: Three cervical cell lines, C33A, HeLa, and SiHa were treated with PTC209. The impacts of PTC209 on BMI1 were investigated using quantitative reverse-transcription PCR assay (qRT-PCR) and western blotting; changes in cell viability, cell cycle distribution, and apoptosis were assessed using cell viability testing, colony formation assay and flow cytometry analyses, respectively. Results: PTC209 exhibited considerably high short-term and long-term cytotoxicities in all tested cervical cancer cell lines regardless of their HPV infection status, TP53 and pRb statuses. PTC209 significantly downregulated the expression of BMI1 in cervical cancer cell lines, and such downregulation led to G0/G1 arrest (p<0.05). Moreover, PTC209 drove more cells into apoptosis (p<0.05). Conclusion: PTC209 (BMI1-targeting agents, in general) represents a novel chemotherapeutic agent with potential in cervical cancer therapy.	[Li, Junan; Poi, Ming] Ohio State Univ, Coll Pharm, Div Pharm Practice & Adm, 500 W 12Th Ave, Columbus, OH 43210 USA; [Li, Junan; Vangundy, Zachary; Poi, Ming] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA; [Vangundy, Zachary; Poi, Ming] Arthur G James Canc Hosp, Dept Pharm, Columbus, OH USA; [Vangundy, Zachary; Poi, Ming] Richard J Solove Res Inst, Columbus, OH USA		Li, JN (corresponding author), Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA.	li.225@osu.edu					Alzrigat M, 2017, ONCOTARGET, V8, P103731, DOI 10.18632/oncotarget.21909; American Cancer Society, 2019, CANC TREATMENT SURVI; Berman TA, 2017, CANCER-AM CANCER SOC, V123, P2219, DOI 10.1002/cncr.30588; Bolomsky A, 2016, J HEMATOL ONCOL, V9, DOI 10.1186/s13045-016-0247-4; Chauhan Subhash C., 2009, V471, P439, DOI 10.1007/978-1-59745-416-2_22; Chen FH, 2011, MED ONCOL, V28, P1201, DOI 10.1007/s12032-010-9634-9; Chen SQ, 2020, J CELL PHYSIOL, V235, P7757, DOI 10.1002/jcp.29382; Chen YC, 2005, CA-CANCER J CLIN, V55, P45, DOI 10.3322/canjclin.55.1.45; Cohen PA, 2019, LANCET, V393, P169, DOI 10.1016/S0140-6736(18)32470-X; Darwish NHE, 2016, ONCOTARGET, V7, P57811, DOI 10.18632/oncotarget.11063; Dey A, 2016, AUTOPHAGY, V12, P659, DOI 10.1080/15548627.2016.1147670; Dimri M, 2016, ONCOTARGET, V7, P36220, DOI 10.18632/oncotarget.8811; Elango R, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-50140-0; Fan TF, 2018, J PINEAL RES, V64, DOI 10.1111/jpi.12457; Gavrilescu MM, 2012, MED-SURG J, V116, P1112; Gray F, 2016, NAT COMMUN, V7, DOI 10.1038/ncomms13343; Honig A, 2010, ANTICANCER RES, V30, P1559; Kaufhold S, 2016, J EXP CLIN CANC RES, V35, DOI 10.1186/s13046-016-0359-2; Kong Y, 2018, CELL CYCLE, V17, P1199, DOI [10.6084/m9.figshare.6466172, 10.1080/15384101.2018.1469872]; Kreso A, 2014, NAT MED, V20, P29, DOI 10.1038/nm.3418; Li JA, 2014, MOL CARCINOGEN, V53, P211, DOI 10.1002/mc.21965; Li JN, 2011, BIOCHEMISTRY-US, V50, P5566, DOI 10.1021/bi200642e; Li ZW, 2014, LAB INVEST, V94, P1431, DOI 10.1038/labinvest.2014.123; Mayr C, 2016, ONCOTARGET, V7, P745, DOI 10.18632/oncotarget.6378; McGinty RK, 2014, NATURE, V514, P591, DOI 10.1038/nature13890; Mourgues L, 2015, LEUKEMIA, V29, P1993, DOI 10.1038/leu.2015.112; Nishida Y, 2015, CANCER SCI, V106, P1705, DOI 10.1111/cas.12833; Ohtaka M, 2017, ANTICANCER RES, V37, P6047, DOI 10.21873/anticanres.12052; Persaud AK, 2019, MOL CARCINOGEN, V58, P2327, DOI 10.1002/mc.23121; Poi MJ, 2017, MOL CARCINOGEN, V56, P1722, DOI 10.1002/mc.22626; Poi MJ, 2014, ANTICANCER RES, V34, P3285; Ramaiah MJ, 2018, GENE, V678, P302, DOI 10.1016/j.gene.2018.08.022; Shahi MH, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0131006; Siegel RL, 2019, CA-CANCER J CLIN, V69, P7, DOI 10.3322/caac.21551; Srinivasan M, 2017, ONCOTARGET, V8, P38731, DOI 10.18632/oncotarget.16317; Tong YQ, 2012, ASIA-PAC J CLIN ONCO, V8, pE55, DOI 10.1111/j.1743-7563.2012.01564.x; Xu JQ, 2019, BIOMATERIALS, V216, DOI 10.1016/j.biomaterials.2019.119247; Xu R, 2019, ONCOL REP, V42, P688, DOI 10.3892/or.2019.7188; Xu R, 2013, HUM PATHOL, V44, P208, DOI 10.1016/j.humpath.2012.02.020; Yoo YA, 2019, JNCI-J NATL CANCER I, V111, P311, DOI 10.1093/jnci/djy142; Zheng WJ, 2019, J CANCER, V10, P5862, DOI 10.7150/jca.31599; Zhu Songyan, 2018, J ATMOS, V9, P1	42	4	4	1	5	INT INST ANTICANCER RESEARCH	ATHENS	EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE	0250-7005	1791-7530		ANTICANCER RES	Anticancer Res.	JAN	2020	40	1					133	141		10.21873/anticanres.13934			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	KY7BB	WOS:000522727700014	31892561	Bronze			2022-04-25	
J	Hu, S; Yin, J; Yan, S; Hu, P; Huang, JZ; Zhang, G; Wang, FQ; Tong, QY; Zhang, YH				Hu, Song; Yin, Jie; Yan, Shan; Hu, Ping; Huang, Jianzheng; Zhang, Geng; Wang, Fuqian; Tong, Qingyi; Zhang, Yonghui			Chaetocochin J, an epipolythiodioxopiperazine alkaloid, induces apoptosis and autophagy in colorectal cancer via AMPK and PI3K/AKT/ mTOR pathways	BIOORGANIC CHEMISTRY			English	Article						Epipolythiodioxopiperazine; Chaetocochin J; Apoptosis; Autophagy; Colorectal cancer		Colorectal cancer (CRC) is the third commonly diagnosed malignancy and the second leading cause of cancer death worldwide. Development of novel chemotherapeutics is crucial. Natural products are the main source of drug discovery, and epipolythiodioxopiperazine (ETP) alkaloids are one kind of them have been reported to have potent biological activities. In the present study, we first isolated Chaetocochin J (CJ), an ETP alkaloid from the secondary metabolites of Chaetomium sp, and studied the anti-CRC activity and mechanism of it. The results showed that CJ exhibits potent proliferation inhibition effect, its IC50 to CRC cells are around 0.5 ?M. CJ also induces apoptosis of CRC cells in a dose-dependent manner, and this effect is stronger than topotecan. In addition, CJ treatment triggers autophagic flux in CRC cells, inhibition of autophagy by chloroquine didn?t affect CJ-induced apoptosis and growth inhibition, suggesting CJ may simultaneously induced apoptosis and autophagy in CRC cells. We further explored the mechanism of action, and found that CJ exerts its anti-CRC function via AMPK and PI3K/AKT/mTOR pathways and further regulation of their downstream signaling cascade in CRC cells, including apoptosis and autophagy. These data potently suggest that CJ may be a potential drug candidate for CRC treatment.	[Hu, Song; Zhang, Geng; Wang, Fuqian] Wuhan 1 Hosp, Dept Pharm, 215 Zhongshan Rd, Wuhan 430022, Hubei, Peoples R China; [Yin, Jie; Yan, Shan; Huang, Jianzheng; Tong, Qingyi; Zhang, Yonghui] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Rongcheng Ctr Biomed, Sch Pharm,Hubei Key Lab Nat Med Chem & Resource E, Wuhan 430030, Hubei, Peoples R China; [Hu, Ping] Hubei Univ, State Key Lab Biocatalysis & Enzyme Engn, Natl & Local Joint Engn Res Ctr High Throughput D, Sch Life Sci,Hubei Collaborat Innovat Ctr Green T, Wuhan 430062, Hubei, Peoples R China; [Wang, Fuqian] Hubei Univ Chinese Med, Fac Pharm, Wuhan 430065, Hubei, Peoples R China		Wang, FQ; Tong, QY; Zhang, YH (corresponding author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Rongcheng Ctr Biomed, Sch Pharm,Hubei Key Lab Nat Med Chem & Resource E, Wuhan 430030, Hubei, Peoples R China.	wangfuqian.c@163.com; qytong@hust.edu.cn; zhangyh@mails.tjmu.edu.cn	Zhang, Yonghui/AGY-9072-2022		Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [5003514027]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31670351]; Natural Science Foundation of Hubei ProvinceNatural Science Foundation of Hubei Province [2020CFB726]; Scientific Research Project of Wuhan Municipal Health Commission [WX20A14]	This work was supported by the Fundamental Research Funds for the Central Universities (5003514027) , the National Natural Science Foundation of China (31670351) , Natural Science Foundation of Hubei Province (2020CFB726) , Scientific Research Project of Wuhan Municipal Health Commission (WX20A14) .	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APR	2021	109								104693	10.1016/j.bioorg.2021.104693		FEB 2021	8	Biochemistry & Molecular Biology; Chemistry, Organic	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	RL7NE	WOS:000639154200005	33609914				2022-04-25	
J	Jo, YK; Roh, SA; Lee, H; Park, NY; Choi, ES; Oh, JH; Park, SJ; Shin, JH; Suh, YA; Lee, EK; Cho, DH; Kim, JC				Jo, Yoon Kyung; Roh, Seon Ae; Lee, Heejin; Park, Na Yeon; Choi, Eun Sun; Oh, Ju-Hee; Park, So Jung; Shin, Ji Hyun; Suh, Young-Ah; Lee, Eun Kyung; Cho, Dong-Hyung; Kim, Jin Cheon			Polypyrimidine tract-binding protein 1-mediated down-regulation of ATG10 facilitates metastasis of colorectal cancer cells	CANCER LETTERS			English	Article						ATG10; Autophagy; PTBP1; Metastasis; EMT	EPITHELIAL-MESENCHYMAL TRANSITION; POSTTRANSCRIPTIONAL REGULATION; TUMOR-SUPPRESSOR; AUTOPHAGY GENE; BREAST-CANCER; N-CADHERIN; PROGRESSION; EXPRESSION; DEATH; SURVIVAL	Autophagy plays complex roles in tumor initiation and development, and the expression of autophagy-related genes (ATGs) is differentially regulated in various cancer cells, depending on their environment. In this study, we analyzed the expressional relationship between polypyrimidine tract-binding protein 1 (PTBP1) and ATG10 in metastatic colorectal cancer. PTBP1 is associated with tumor metastasis in primary colorectal tumors and colorectal cancer liver metastasis (CLM) tissues. In addition, PTPB1 directly interacts with mRNA of ATG10, and regulates ATG10 expression level in colorectal cancer cells. Ectopic expression of PTBP1 decreased ATG10 expression, whereas down-regulation of PTBP1 increased ATG10 level. In contrast to PTBP1, expression of ATG10 was decreased in CLM tissues. Knock down of ATG10 promoted cell migration and invasion of colorectal cancer cells. Moreover, depletion of ATG10 modulated epithelial-mesenchymal transition-associated proteins in colorectal cancer cells: N-cadherin, TCF-8/ZEB1, and CD44 were up-regulated, whereas E-cadherin was down-regulated. Taken together, our findings suggest that expression of ATG10 negatively regulated by PTBP1 is associated with metastasis of colorectal cancer cells. (C) 2016 Elsevier Ireland Ltd. All rights reserved.	[Jo, Yoon Kyung; Park, Na Yeon; Choi, Eun Sun; Park, So Jung; Shin, Ji Hyun; Cho, Dong-Hyung] Kyung Hee Univ, Grad Sch East West Med Sci, Dept Gerontol, Yongin, South Korea; [Roh, Seon Ae; Oh, Ju-Hee; Suh, Young-Ah; Kim, Jin Cheon] Asan Med Ctr, Asan Inst Life Sci, Seoul, South Korea; [Lee, Heejin; Lee, Eun Kyung] Catholic Univ Korea, Coll Med, Dept Biochem, Seoul, South Korea; [Kim, Jin Cheon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Surg, 88,Olymp Ro 43 Gil, Seoul 05505, South Korea		Kim, JC (corresponding author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Surg, 88,Olymp Ro 43 Gil, Seoul 05505, South Korea.; Cho, DH (corresponding author), Kyung Hee Univ, Grad Sch East West Med Sci, 1732,Deogyeong Daero, Yongin 17014, Gyeonggi Do, South Korea.	dhcho@khu.ac.kr; jckim@amc.seoul.kr		Oh, Ju Hee/0000-0003-2864-7677	National Research Foundation, Ministry of Science, ICT and Future Planning, Republic of Korea [NRF-2013R1A2A1A03070986, 2013R1A1A1058361]	This study was supported by grants from the National Research Foundation (NRF-2013R1A2A1A03070986 and 2013R1A1A1058361), Ministry of Science, ICT and Future Planning, Republic of Korea.	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JAN 28	2017	385						21	27		10.1016/j.canlet.2016.11.002			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EF7FV	WOS:000390496400003	27836735				2022-04-25	
J	Habibzadeh, P; Dastsooz, H; Eshraghi, M; Los, MJ; Klionsky, DJ; Ghavami, S				Habibzadeh, Parham; Dastsooz, Hassan; Eshraghi, Mehdi; Los, Marek J.; Klionsky, Daniel J.; Ghavami, Saeid			Autophagy: The Potential Link between SARS-CoV-2 and Cancer	CANCERS			English	Article						colorectal neoplasms; COVID-19; gastrointestinal neoplasms; immune checkpoint inhibitors; neoplasms; oncogenic viruses; oncolytic virotherapy; post-acute COVID-19 syndrome; reactive oxygen species; tumor escape	UNFOLDED PROTEIN RESPONSE; BIOLOGICAL FUNCTIONS; METABOLISM; MECHANISMS; STRESS; GENES	Simple Summary Coronavirus disease 2019 (COVID-19) has led to a global crisis. With the increasing number of individuals infected worldwide, the long-term consequences of this disease have become an active area of research. The constellation of symptoms COVID-19 survivors suffer from is commonly referred to as post-acute COVID-19 syndrome in the scientific literature. In this paper, we discuss the potential long-term complications of this infection resulting from the persistence of the viral particles in body tissues interacting with host cells' autophagy machinery in the context of the development of cancer, cancer progression and metastasis, as well as response to treatment. We also propose a structured framework for future studies to investigate the potential impact of COVID-19 infection on cancer. COVID-19 infection survivors suffer from a constellation of symptoms referred to as post-acute COVID-19 syndrome. However, in the wake of recent evidence highlighting the long-term persistence of SARS-CoV-2 antigens in tissues and emerging information regarding the interaction between SARS-CoV-2 proteins and various components of the host cell macroautophagy/autophagy machinery, the unforeseen long-term consequences of this infection, such as increased risk of malignancies, should be explored. Although SARS-CoV-2 is not considered an oncogenic virus, the possibility of increased risk of cancer among COVID-19 survivors cannot be ruled out. Herein, we provide an overview of the possible mechanisms leading to cancer development, particularly obesity-related cancers (e.g., colorectal cancer), resulting from defects in autophagy and the blockade of the autophagic flux, and also immune escape in COVID-19 survivors. We also highlight the potential long-term implications of COVID-19 infection in the prognosis of patients with cancer and their response to different cancer treatments. Finally, we consider future directions for further investigations on this matter.	[Habibzadeh, Parham] Shiraz Univ Med Sci, Inst Hlth, Res Ctr Hlth Sci, Shiraz 7134814336, Iran; [Dastsooz, Hassan] Univ Turin, Dept Life Sci & Syst Biol, Via Accademia,Albertina 13, I-10123 Turin, Italy; [Dastsooz, Hassan] IRCCS, IIGM Italian Inst Genom Med, I-10126 Turin, Italy; [Dastsooz, Hassan] IRCCS, FPO, Candiolo Canc Inst, I-10060 Turin, Italy; [Eshraghi, Mehdi; Ghavami, Saeid] Univ Manitoba, Max Rady Coll Med, Rady Fac Hlth Sci, Dept Human Anat & Cell Sci, Winnipeg, MB R3E 0J9, Canada; [Los, Marek J.] Silesian Tech Univ, Biotechnol Ctr, PL-44100 Gliwice, Poland; [Klionsky, Daniel J.] Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA; [Ghavami, Saeid] Univ Manitoba, Canc Care Manitoba, Res Inst Oncol & Hematol, Winnipeg, MB R3E 0V9, Canada; [Ghavami, Saeid] Katowice Sch Technol, Fac Med, Ul Rolna 43, PL-40555 Katowice, Poland		Ghavami, S (corresponding author), Univ Manitoba, Max Rady Coll Med, Rady Fac Hlth Sci, Dept Human Anat & Cell Sci, Winnipeg, MB R3E 0J9, Canada.; Los, MJ (corresponding author), Silesian Tech Univ, Biotechnol Ctr, PL-44100 Gliwice, Poland.; Ghavami, S (corresponding author), Univ Manitoba, Canc Care Manitoba, Res Inst Oncol & Hematol, Winnipeg, MB R3E 0V9, Canada.; Ghavami, S (corresponding author), Katowice Sch Technol, Fac Med, Ul Rolna 43, PL-40555 Katowice, Poland.	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J	Zhang, JH; Hunnmersone, M; Matthews, CS; Stevens, MFG; Bradshaw, TD				Zhang, Jihong; Hunnmersone, Marc; Matthews, Charles S.; Stevens, Malcolm F. G.; Bradshaw, Tracey D.			N3-Substituted Temozolomide Analogs Overcome Methylguanine-DNA Methyltransferase and Mismatch Repair Precipitating Apoptotic and Autophagic Cancer Cell Death	ONCOLOGY			English	Article						Glioblastoma multiforme; Temozolomide; Methylguanine-DNA methyltransferase; Mismatch repair; Apoptosis; Autophagy	MALIGNANT GLIOMA-CELLS; MONITORING AUTOPHAGY; INDUCED CYTOTOXICITY; ANTICANCER AGENTS; P53 FUNCTION; ALKYLTRANSFERASE; SENSITIVITY; INHIBITION; ARREST; LINES	Glioblastoma multiforme (GBM) treatment includes temozolomide (TMZ) chemotherapy. O6-Methylguanine lesions are repaired by methylguanine-DNA methyltransferase (MGMT). Response to TMZ requires low MGMT and functional mismatch repair (MMR); resistance, conferred by MGMT or MMR deficiency, represents a barrier to successful treatment. TMZ analogs were synthesized, substituting N3-methyl with propargyl (1) or sulfoxide (2). MTT assays were conducted in SNB19 and U373 isogenic glioma cell lines (V = vector control; M = MGMT-transfected). TMZ potency was reduced >5-fold in SNB19M and U373M cells; in contrast, MGMT-expressing cells were equisensitive as vector controls to analogs 1 and 2. GI(50) values <50 mu m of analogs 1 or 2 were detected in V cells possessing acquired TMZ resistance: SNB19VR (hMSH6 loss) and U373VR (MGMT upregulation). Analogs 1 and 2 inhibited MMR-deficient colorectal carcinoma cell growth (irrespective of p53); G2/M cell cycle arrest preceded apoptosis. gamma H2AX foci inferred the generation of DNA double-strand breaks by analogs 1 and 2. Acridine orange-stained vesicles, intracellular punctate GFP-LC3 protein and double-membraned autophagosomes indicate that TMZ, 1 and 2 induce autophagy in apoptotis-resistant GBM cells. Analogs 1 and 2 elicit in vitro antitumor activity irrespective of MGMT, M MR and p53. Such imidazotetrazines may treat MGMT+ GBM and possess broader spectrum activity causing apoptosis and autophagy in malignancies which evade apoptosis. (C) 2014 S. Karger AG, Basel	[Zhang, Jihong] Kunming Univ Sci & Technol, Fac Med, Kunming, Peoples R China; [Hunnmersone, Marc] Pharminox Ltd, Nottingham, England; [Matthews, Charles S.; Stevens, Malcolm F. G.; Bradshaw, Tracey D.] Univ Nottingham, Ctr Biomol Sci, Nottingham NG7 2RD, England		Bradshaw, TD (corresponding author), Univ Nottingham, Ctr Biomol Sci, Univ Pk, Nottingham NG7 2RD, England.	tracey.bradshaw@nottingham.ac.uk			Pharminox Ltd.; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81260501]	Financial support for all work described herein was provided by Pharminox Ltd. and by the National Natural Science Foundation of China (No. 81260501).	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J	Koziol, E; Luca, SV; Marcourt, L; Nour, M; Hnawia, E; Jakubowicz-Gil, J; Paduch, R; Mroczek, T; Wolfender, JL; Skalicka-Wozniak, K				Koziol, Ewelina; Luca, Simon Vlad; Marcourt, Laurence; Nour, Mohamed; Hnawia, Edouard; Jakubowicz-Gil, Joanna; Paduch, Roman; Mroczek, Tomasz; Wolfender, Jean-Luc; Skalicka-Wozniak, Krystyna			Efficient extraction and isolation of skimmianine from New Caledonian plant Medicosma leratii and evaluation of its effects on apoptosis, necrosis, and autophagy	PHYTOCHEMISTRY LETTERS			English	Article						Rutaceae; High-performance countercurrent chromatography; Programmed cell death; Acridone alkaloids; Sarcodifurine C	QUINOLINE ALKALOIDS; ACRIDONE ALKALOIDS; SORAFENIB; LEAVES; BARK	This study was aimed at improving the current knowledge about the new Caledonian plant species Medicosma leratii, by developing efficient methods of extraction and isolation of specialized metabolites. Ultrasound-assisted extraction (UAE) significantly gave higher yields of the furoquinoline alkaloid skimmianine (22.34 mg/100 g) than accelerated solvent extraction (ASE, 1.37-12.36 mg/100 g). High-performance countercurrent chromatographic (HPCCC) separation of the methanol leaf extract with n-hexane-ethyl acetate-methanol-water (6:5:6:5 v/v) afforded skimmianine (1, 7.55 mg, HPLC-DAD purity 99.4%), normelicopidine (3, 1.87 mg, 95.6%), normelicopicine (4, 2.63 mg, 97.3%) and a new furoquinoline alkaloid named sarcodifurine C (2, 1.20 mg, 95.8%). The effect of the crude extract and its main constituent, skimmianine, on apoptosis, autophagy, and necrosis induction in tumor cells has also been investigated. The crude extract and skimmianine were found to be effective apoptosis inducers in HeLa cervical cancer cell line, but not in colon cancer SW620 and HT-29 cells. Additionally, skimmianine effectively potentiated the pro-apoptotic properties of the antincancer agent sorafenib in cervical cancer cells.	[Koziol, Ewelina; Luca, Simon Vlad; Mroczek, Tomasz; Skalicka-Wozniak, Krystyna] Med Univ Lublin, Dept Pharmacognosy, Med Plant Unit, Chodzki 1, PL-20093 Lublin, Poland; [Luca, Simon Vlad] Grigore T Pope Univ Med & Pharm Iasi, Dept Pharmacognosy, Univ 16, Iasi 700115, Romania; [Marcourt, Laurence; Wolfender, Jean-Luc] Univ Lausanne, Univ Geneva, EPGL, Sch Pharmaceut Sci,CMU, Michel Servet 1, CH-1211 Geneva 4, Switzerland; [Nour, Mohamed; Hnawia, Edouard] Univ New Caledonia, EA 4243, LIVE, BP R4, Noumea 98851, New Caledonia; [Jakubowicz-Gil, Joanna] Marie Curie Sklodowska Univ, Dept Comparat Anat & Anthropol, Akad 19, PL-20033 Lublin, Poland; [Paduch, Roman] Marie Curie Sklodowska Univ, Dept Virol & Immunol, Akad 19, PL-20033 Lublin, Poland		Luca, SV (corresponding author), Grigore T Pope Univ Med & Pharm Iasi, Dept Pharmacognosy, Univ 16, Iasi 700115, Romania.	simon-vlad.v.luca@d.umfiasi.ro	Luca, Vlad/AAP-6225-2020; Jakubowicz-Gil, Joanna/AAK-3561-2020; Skalicka-Woźniak, Krystyna/AAJ-5579-2020; Luca, Simon Vlad/AAF-2613-2019	Jakubowicz-Gil, Joanna/0000-0003-2077-804X; Paduch, Roman/0000-0001-9779-7252; Skalicka-Wozniak, Krystyna/0000-0002-9313-5929; Koziol, Ewelina/0000-0002-8639-4981; Mroczek, Tomasz/0000-0002-5267-7182	Medical University of Lublin, Poland [DS28]; Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission [316030_164095]	This work was financially supported by Medical University of Lublin, Poland, grant number DS28. The School of Pharmaceutical Sciences of the University of Geneva (Prof. J-L. Wolfender) is thankful to the Swiss National Science Foundation for the support in the acquisition of the NMR 600 MHz (SNF R'Equip grant 316030_164095).	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Lett.	APR	2019	30						224	230		10.1016/j.phytol.2018.12.002			7	Plant Sciences; Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Plant Sciences; Pharmacology & Pharmacy	HP0NX	WOS:000461363900045					2022-04-25	
J	Russo, M; Moccia, S; Bilotto, S; Spagnuolo, C; Durante, M; Lenucci, MS; Mita, G; Volpe, MG; Aquino, RP; Russo, GL				Russo, Maria; Moccia, Stefania; Bilotto, Stefania; Spagnuolo, Carmela; Durante, Miriana; Lenucci, Marcello Salvatore; Mita, Giovanni; Volpe, Maria Grazia; Aquino, Rita Patrizia; Russo, Gian Luigi			A Carotenoid Extract from a Southern Italian Cultivar of Pumpkin Triggers Nonprotective Autophagy in Malignant Cells	OXIDATIVE MEDICINE AND CELLULAR LONGEVITY			English	Article							TRANS-RETINOIC ACID; CHRONIC LYMPHOCYTIC-LEUKEMIA; INDUCED CYTOTOXICITY; LINE SAOS-2; CANCER; DIFFERENTIATION; MODULATION; GROWTH; PHOSPHORYLATION; MECHANISMS	Carotenoids, including beta-carotene, lycopene, and derivatives, such as retinoic acid, have been studied for their significant antiproliferative and differentiating activity on cancer cells in experimental models and in clinics. We are presenting here data on the mechanism of action of a carotenoid-enriched extract obtained from the pumpkin Cucurbita moschata, variety "long of Naples," on two malignant human cell lines, Caco-2 and SAOs, derived from a colon adenocarcinoma and an osteosarcoma, respectively. The carotenoid extract has been obtained from pumpkin pulp and seeds by supercritical CO2 extraction and employed to prepare oil-in-water nanoemulsions. The nanoemulsions, applied at a final carotenoid concentration of 200-400 mu g/ml, were not cytotoxic, but induced a delay in cell growth of about 40% in both SAOs and Caco-2 cell lines. This effect was associated with the activation of a "nonprotective" form of autophagy and, in SAOs cells, to the induction of cell differentiation via a mechanism that involved AMPK activation. Our data suggest the presence of a pool of bioactive compounds in the carotenoid-enriched extract, acting additively, or synergistically, to delay cell growth in cancer cells.	[Russo, Maria; Moccia, Stefania; Bilotto, Stefania; Spagnuolo, Carmela; Volpe, Maria Grazia; Russo, Gian Luigi] CNR, Ist Sci Alimentaz, I-83100 Avellino, Italy; [Durante, Miriana; Mita, Giovanni] CNR, Ist Sci Prod Alimentari, I-73100 Lecce, Italy; [Lenucci, Marcello Salvatore] Univ Salento, Dipartimento Sci & Tecnol Biol & Ambientali, I-73100 Lecce, Italy; [Aquino, Rita Patrizia] Univ Salerno, Dipartimento Farm, Fisciano, Italy		Russo, GL (corresponding author), CNR, Ist Sci Alimentaz, I-83100 Avellino, Italy.	glrusso@isa.cnr.it	Russo, Gian Luigi/D-6333-2012; moccia, stefania/ABE-3470-2020; Mita, Giovanni/B-6575-2015; Durante, Miriana/AAV-9282-2020; Russo, Maria/E-8585-2011; Lenucci, Marcello Salvatore/N-7174-2015	Russo, Gian Luigi/0000-0001-9321-1613; Mita, Giovanni/0000-0002-0850-1681; Russo, Maria/0000-0001-8385-9184; aquino, rita patrizia/0000-0002-9754-4244; Lenucci, Marcello Salvatore/0000-0002-6493-9549; Volpe, Maria Grazia/0000-0003-0777-0473	Italian Ministry of Economy and Finance [191/2009]	The authors thank Dr. Giuseppe Mazzarella for the kind assistance in using confocal microscopy. This work was supported by the following: C.I.S.I.A. project "Innovazione e Sviluppo del Mezzogiorno-Conoscenze Integrate per Sostenibilita ed Innovazione del Made in Italy Agroalimentare-Legge 191/2009" from the Italian Ministry of Economy and Finance to the National Research Council.	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Cell. Longev.		2017	2017								7468538	10.1155/2017/7468538			15	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	FR4SC	WOS:000419055000001	29430284	Green Published, gold, Green Submitted			2022-04-25	
J	Liu, PF; Leung, CM; Chang, YH; Cheng, JS; Chen, JJ; Weng, CJ; Tsai, KW; Hsu, CJ; Liu, YC; Hsu, PC; Pan, HW; Shu, CW				Liu, Pei-Feng; Leung, Chung-Man; Chang, Yu-Hsiang; Cheng, Jin-Shiung; Chen, Jih-Jung; Weng, Chung-Jeu; Tsai, Kuo-Wang; Hsu, Chien-Jen; Liu, Yen-Chen; Hsu, Ping-Chi; Pan, Hung-Wei; Shu, Chih-Wen			ATG4B promotes colorectal cancer growth independent of autophagic flux	AUTOPHAGY			English	Article						ATG4B; autophagy; CCND1; colorectal cancer; MTOR; tumor proliferation	CYCLIN D1 EXPRESSION; BECLIN 1; TUMORIGENESIS; LC3; PHOSPHORYLATION; DEGRADATION; LIPIDATION; P62/SQSTM1; ACTIVATION; INHIBITORS	Autophagy is reported to suppress tumor proliferation, whereas deficiency of autophagy is associated with tumorigenesis. ATG4B is a deubiquitin-like protease that plays dual roles in the core machinery of autophagy; however, little is known about the role of ATG4B on autophagy and proliferation in tumor cells. In this study, we found that ATG4B knockdown induced autophagic flux and reduced CCND1 expression to inhibit G(1)/S phase transition of cell cycle in colorectal cancer cell lines, indicating functional dominance of ATG4B on autophagy inhibition and tumor proliferation in cancer cells. Interestingly, based on the genetic and pharmacological ablation of autophagy, the growth arrest induced by silencing ATG4B was independent of autophagic flux. Moreover, dephosphorylation of MTOR was involved in reduced CCND1 expression and G(1)/S phase transition in both cells and xenograft tumors with depletion of ATG4B. Furthermore, ATG4B expression was significantly increased in tumor cells of colorectal cancer patients compared with adjacent normal cells. The elevated expression of ATG4B was highly correlated with CCND1 expression, consistently supporting the notion that ATG4B might contribute to MTOR-CCND1 signaling for G(1)/S phase transition in colorectal cancer cells. Thus, we report that ATG4B independently plays a role as a positive regulator on tumor proliferation and a negative regulator on autophagy in colorectal cancer cells. These results suggest that ATG4B is a potential biomarker and drug target for cancer therapy.	[Liu, Pei-Feng; Tsai, Kuo-Wang; Hsu, Chien-Jen; Liu, Yen-Chen; Pan, Hung-Wei; Shu, Chih-Wen] Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung, Taiwan; [Liu, Pei-Feng] Fooyin Univ, Dept Biotechnol, Kaohsiung, Taiwan; [Leung, Chung-Man] Kaohsiung Vet Gen Hosp, Dept Radiat Oncol, Kaohsiung, Taiwan; [Leung, Chung-Man; Hsu, Ping-Chi] Natl Kaohsiung First Univ Sci & Technol, Dept Safety Hlth & Environm Engn, Kaohsiung, Taiwan; [Chang, Yu-Hsiang] Kaohsiung Vet Gen Hosp, Dept Pediat, Kaohsiung, Taiwan; [Chang, Yu-Hsiang] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan; [Chang, Yu-Hsiang] Tajen Univ, Dept Nursing, Pingtung, Taiwan; [Cheng, Jin-Shiung] Kaohsiung Vet Gen Hosp, Dept Internal Med, Kaohsiung, Taiwan; [Chen, Jih-Jung] Tajen Univ, Dept Pharm, Pingtung, Taiwan; [Chen, Jih-Jung] Tajen Univ, Grad Inst Pharmaceut Technol, Pingtung, Taiwan; [Weng, Chung-Jeu] Kaohsiung Armed Forces Gen Hosp, Zuoying Branch, Dept Obstet Gynecol, Kaohsiung, Taiwan		Shu, CW (corresponding author), Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung, Taiwan.	hwpan@vghks.gov.tw; cwshu@vghks.gov.tw	Shu, Chih-Wen/AAE-9652-2019	Tsai, Kuo-Wang/0000-0002-9028-9834; Hsu, Ping-Chi/0000-0003-2562-1463; Shu, Chih-Wen/0000-0002-7774-0002; Liu, Pei-Feng/0000-0002-7849-8940	National Science Council (NSC)Ministry of Science and Technology, Taiwan [101-2311-B-075B-001, 102-2311-B-075B-001]; Kaohsiung Veterans General Hospital [VGHKS102-007, VGHKS103-G01-1, VGHKS100-058]	We thank Dr Lopez-Otin for kindly providing Atg4b<SUP>+/+</SUP> and atg4b<SUP>-/-</SUP> mouse embryonic fibroblast (MEF) cells from which we generated immortalized Atg4b<SUP>+/+</SUP> and atg4b<SUP>-/-</SUP> 3T3 cells. We also thank Dr Jie Chen and Dr Philip Hinds for sharing plasmids FLAG-MTOR and HA-CCND1, respectively. This work was supported by National Science Council (NSC 101 and 102-2311-B-075B-001 to C-WS) and Kaohsiung Veterans General Hospital (VGHKS102-007 to C-WS, VGHKS103-G01-1 to C-JH, and VGHKS100-058 to C-ML).	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J	Choi, P; Park, JY; Kim, T; Park, SH; Kim, HK; Kang, KS; Ham, J				Choi, Pilju; Park, Jun Yeon; Kim, Taejung; Park, Soon-Hye; Kim, Ho-Kyong; Kang, Ki Sung; Ham, Jungyeoh			Improved anticancer effect of ginseng extract by microwave-assisted processing through the generation of ginsenosides Rg3, Rg5 and Rk1	JOURNAL OF FUNCTIONAL FOODS			English	Article						Ginseng; Microwave; Ginsenoside; Cervical cancer; Cell death	SCAVENGING ACTIVITY CHANGES; AMERICAN GINSENG; APOPTOSIS; RE; ANTIOXIDANT; INHIBITION; INCREASE; MIXTURE	In this study, we demonstrated the efficient structural conversion of ginsenosides, which enhances the anticancer activity of ginseng by microwave irradiation. The microwave-irradiated product of ginseng (MG) had a higher content of ginsenosides, Rg3+Rg5+Rk1, particularly Rg5 and Rk1, and, thus, has an increased medicinal effect. To confirm the anticancer effect of MG, it was tested in 5 human cancer cell lines (cervical cancer HeLa, gastric cancer AGS, colon cancer HCT-116, lung cancer A549, and liver cancer HepG2 cells). Anti-proliferation results for 5 human cancer cell lines treated with ginseng extracts indicate that HeLa cells treated with MG showed the highest activity with an IC50 value of 130.1 mu g/mL. MG also suppressed the growth of human cervical cancer cell xenografts in athymic nude mice as an in vivo model. This growth suppression by MG is associated with the induction of cell death and autophagy. Moreover, there were no toxic sign or decrease in renal and hepatic function in mice administered with MG. Therefore, heat processing by microwave irradiation is a useful method to enhance the anticancer effect of ginseng as it increases the content of ginsenosides, Rg3, Rg5, and Rk1. (C) 2015 Elsevier Ltd. All rights reserved.	[Choi, Pilju; Kim, Taejung; Ham, Jungyeoh] Korea Inst Sci & Technol, Gangneung Inst Nat Prod, Kangnung 210340, South Korea; [Park, Jun Yeon; Kang, Ki Sung] Gachon Univ, Coll Korean Med, Songnam 461701, South Korea; [Park, Soon-Hye; Kim, Ho-Kyong] Richwood Pharmaceut Co LTD, Seoul 100704, South Korea		Kang, KS (corresponding author), Gachon Univ, Coll Korean Med, Songnam 461701, South Korea.	kkang@gachon.ac.kr; ham0606@kist.re.kr			Korea Institute of Science and Technology institutional program [2Z04390]; Ministry of Trade, Industry & Energy (MOTIE, Korea) [N0000885]	This work was supported by the Korea Institute of Science and Technology institutional program (2Z04390). This research was also conducted under the industrial infrastructure program for fundamental technologies (N0000885) which is funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea).	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J	Jeong, S; Kim, BG; Kim, DY; Kim, BR; Kim, JL; Park, SH; Na, YJ; Jo, MJ; Yun, HK; Jeong, YA; Kim, HJ; Lee, SI; Kim, HD; Kim, DH; Oh, SC; Lee, DH				Jeong, Soyeon; Kim, Bu Gyeom; Kim, Dae Yeong; Kim, Bo Ram; Kim, Jung Lim; Park, Seong Hye; Na, Yoo Jin; Jo, Min Jee; Yun, Hye Kyeong; Jeong, Yoon A.; Kim, Hong Jun; Lee, Sun Il; Kim, Han Do; Kim, Dae Hyun; Oh, Sang Cheul; Lee, Dae-Hee			Cannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3-and SOD2-Induced Autophagy in Human Colorectal Cancer Cells	CANCERS			English	Article						oxaliplatin resistance; colorectal cancer; CBD; NOS3; autophagy; mitochondrial dysfunction	NITRIC-OXIDE SYNTHASE; MECHANISMS; STRESS; GROWTH	Although oxaliplatin is an effective chemotherapeutic drug for colorectal cancer (CRC) treatment, patients often develop resistance to it. Therefore, a new strategy for CRC treatment is needed. The purpose of this study was to determine the effect of cannabidiol (CBD), one of the components of the cannabis plant, in overcoming oxaliplatin resistance in CRC cells. We established oxaliplatin-resistant cell lines, DLD-1 R and colo205 R, in CRC DLD-1 and colo205 cells. Autophagic cell death was induced when oxaliplatin-resistant cells were treated with both oxaliplatin and CBD. Additionally, phosphorylation of nitric oxide synthase 3 (NOS3) was increased in oxaliplatin-resistant cells compared to that in parent cells. Combined treatment with oxaliplatin and CBD reduced phospho-NOS3 levels and nitric oxide (NO) production and resulted in the production of reactive oxygen species (ROS) by reducing the levels of superoxide dismutase 2, an antioxidant present in the mitochondria, causing mitochondrial dysfunction. Taken together, these results suggest that elevated phosphorylation of NOS3 is essential for oxaliplatin resistance. The combination of oxaliplatin and CBD decreased NOS3 phosphorylation, which resulted in autophagy, by inducing the overproduction of ROS through mitochondrial dysfunction, thus overcoming oxaliplatin resistance.	[Jeong, Soyeon; Kim, Bo Ram; Kim, Jung Lim; Oh, Sang Cheul; Lee, Dae-Hee] Korea Univ, Dept Internal Med, Div Oncol Hematol, Guro Hosp, 148 Gurodong Gil, Seoul 08308, South Korea; [Kim, Bu Gyeom; Kim, Dae Yeong; Park, Seong Hye; Na, Yoo Jin; Jo, Min Jee; Yun, Hye Kyeong; Jeong, Yoon A.; Oh, Sang Cheul; Lee, Dae-Hee] Korea Univ, Coll Med, Grad Sch Med, Seoul 08308, South Korea; [Kim, Hong Jun] Kyung Hee Univ, Dept Internal Med, Div Oncol, Sch Med, 23 Kyung Hee Dae Ro, Seoul 02447, South Korea; [Lee, Sun Il] Korea Univ, Coll Med, Dept Surg, Guro Hosp, Seoul 08308, South Korea; [Kim, Han Do; Kim, Dae Hyun] Kaiyon Bio Tech Co Ltd, 226 Gamasan Ro, Seoul 08308, South Korea		Oh, SC; Lee, DH (corresponding author), Korea Univ, Dept Internal Med, Div Oncol Hematol, Guro Hosp, 148 Gurodong Gil, Seoul 08308, South Korea.; Oh, SC; Lee, DH (corresponding author), Korea Univ, Coll Med, Grad Sch Med, Seoul 08308, South Korea.	jensyj85@gmail.com; qnrua10047@naver.com; derrickdyblue22@gmail.com; ilovewish777@naver.com; clickkjl@naver.com; psh3938@hanmail.net; wing1278@naver.com; minjeeyoyo@nate.com; katecoco@hanmail.net; leomi2614@naver.com; xpassion84@naver.com; silee@korea.ac.kr; howard@kaiyonbiotech.com; dkim238@kaiyonbiotech.com; sachoh@korea.ac.kr; neogene@korea.ac.kr		Jeong, Soyeon/0000-0002-4568-4579	National Research Foundation (NRF) of Korea - Korean government (MSIP) [NRF-2017R1A2B2011684, NRF-2017R1D1A1B03030703]; Business for Cooperative R&D Between Industry, Academy, and Research Institute - Korea Small and Medium Business Administration [C0566291]	This work was supported by a National Research Foundation (NRF) of Korea grant funded by the Korean government (MSIP, NRF-2017R1A2B2011684 and NRF-2017R1D1A1B03030703) and by the Business for Cooperative R&D Between Industry, Academy, and Research Institute funded by the Korea Small and Medium Business Administration (C0566291).	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J	Khan, MZI; Law, HKW				Islam Khan, Md Zahirul; Law, Helen Ka Wai			RAMS11 promotes CRC through mTOR-dependent inhibition of autophagy, suppression of apoptosis, and promotion of epithelial-mesenchymal transition	CANCER CELL INTERNATIONAL			English	Article						LncRNAs; RAMS11; CRC; Autophagy; Apoptosis; EMT	LONG NONCODING RNAS; SIGNALING PATHWAY; MECHANISMS	Background Long non-coding RNAs (lncRNAs), a class of non-coding RNAs (ncRNAs) associated with diverse biological processes of cells. Over the past decades, cumulating research evidences revealed that abnormal expressions of lncRNAs are associated with colorectal cancer (CRC) initiation, progression, metastasis, and resistance to therapies. Moreover, their usefulness as candidate biomarkers for CRC diagnosis and prognosis are well evident throughout previous literature. In the current study, we examined the role and molecular mechanisms of newly identified lncRNA named RNA associated with metastasis-11 (RAMS11) in CRC development. Methods The expression of RAMS11 in CRC cell lines DLD-1, HT-29, HCT-116, and SW480 and colon normal cells CCD-112-CoN were evaluated by quantitative RT-qPCR. The results showed that the RAMS11 is significantly upregulated in CRC cell lines compared to the normal cells. The CCK-8 proliferation assay, colony formation assay, and migration assay were performed to evaluate the biological and physiological functions of RAMS11 in vitro. To decipher the molecular mechanisms of RAMS11 medicated CRC progression, we further performed western blot analysis of the key pathway proteins (e.g., AMPK, AKT, and mTOR). Results Our results revealed that higher expression of RAMS11 is associated with increased CRC proliferation, migration, and development of metastasis. Knockdown of RAMS11 induced autophagy, apoptosis along with reduction of epithelial-mesenchymal transition (EMT) suggesting that RAMS11 is involved in CRC progression. The molecular mechanisms of RAMS11 indicated that knockdown of RAMS11 significantly inhibited CRC carcinogenesis through mTOR-dependent autophagy induction. Conclusions In sum, our results suggested that RAMS11 is an important oncogene in CRC pathogenesis. Targeting RAMS11 could be a potential therapeutic strategy for CRC management.	[Islam Khan, Md Zahirul; Law, Helen Ka Wai] Hong Kong Polytech Univ, Fac Hlth & Social Sci, Dept Hlth Technol & Informat, Hung Hom, Hong Kong, Peoples R China		Law, HKW (corresponding author), Hong Kong Polytech Univ, Fac Hlth & Social Sci, Dept Hlth Technol & Informat, Hung Hom, Hong Kong, Peoples R China.	hthelen@polyu.edu.hk		Islam Khan, Md Zahirul/0000-0001-7048-2613	Departmental Seeding Fund; Internal Institutional Research Fund [P0031318-UAHS]; Hong Kong Polytechnic UniversityHong Kong Polytechnic University	This project is partially supported by: (1) Research grant to HKL including, Departmental Seeding Fund and Internal Institutional Research Fund (P0031318-UAHS). (2) Postgraduate studentship from The Hong Kong Polytechnic University for ZIK.	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JUN 26	2021	21	1							321	10.1186/s12935-021-02023-6			11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	TC3ZG	WOS:000668579900002	34174900	Green Submitted, Green Published, gold			2022-04-25	
J	Prevarskaya, N; Skryma, R; Shuba, Y				Prevarskaya, Natalia; Skryma, Roman; Shuba, Yaroslav			Targeting Ca2+ transport in cancer: close reality or long perspective?	EXPERT OPINION ON THERAPEUTIC TARGETS			English	Review						angiogenesis; apoptosis; autophagy; Ca2+ channels; Ca2+ pumps; cancer; migration; proliferation	ENDOPLASMIC-RETICULUM STRESS; PROSTATE-CANCER; CELL-PROLIFERATION; CARDIAC-GLYCOSIDES; COLON-CANCER; INTRACELLULAR CALCIUM; ION CHANNELS; TRP CHANNELS; APOPTOTIC RESISTANCE; REGULATES APOPTOSIS	Introduction: Cancer is caused by defects in the mechanisms underlying cell proliferation, death and migration. Calcium ions are central to all of these phenomena, serving as major signalling agents with the spatial localisation, magnitude and temporal characteristics of calcium signals ultimately determining cell's fate. The transformation of a normal cell into a malignant derivative is associated with a major rearrangement of Ca2+ pumps, Na/Ca exchangers and Ca2+ channels, which leads to enhanced proliferation and invasion under compromised/impaired ability to die. Areas covered: This paper examines the changes in Ca2+ signalling and the mechanisms that underlie the passage from normal to pathological cell growth and death control. Understanding these changes and identifying the molecular players involved provide new perspectives for cancer treatment. Expert opinion: Despite compelling evidence that the disruption of Ca2+ homeostasis in cancer cells leads to the promotion of certain malignant phenotypes as well as the identification of key Ca2+-transporting molecules whose altered expression and/or function underlies pathological changes, the therapeutic utilisation of these findings for cancer treatment is still at its infancy. However, the rapid development of the field warrants the development of improved molecular Ca2+ transport-targeting tools for cancer diagnosis and treatment.	[Prevarskaya, Natalia] INSERM, U1003, Lab Physiol Cellulaire, Equipe Labellisee Ligue Canc, F-59650 Villeneuve Dascq, France; [Skryma, Roman] Univ Lille 1, Lab Excellence Ion Channels Sci & Therapeut, F-59650 Villeneuve Dascq, France; [Shuba, Yaroslav] NASU, Bogomoletz Inst Physiol, UA-01024 Kiev 24, Ukraine; [Shuba, Yaroslav] NASU, Int Ctr Mol Physiol, UA-01024 Kiev 24, Ukraine; [Shuba, Yaroslav] State Key Lab Mol & Cellular Biol, Kiev, Ukraine		Prevarskaya, N (corresponding author), INSERM, U1003, Lab Physiol Cellulaire, Equipe Labellisee Ligue Canc, F-59650 Villeneuve Dascq, France.	Natacha.Prevarskaya@univ-lille1.fr	Shuba, Yaroslav/AAT-6758-2021	Prevarskaya, natacha/0000-0003-0316-197X	Inserm (Institut National de la Sante et de la Recherche Medicale)Institut National de la Sante et de la Recherche Medicale (Inserm); Ligue Nationale Contre le CancerLigue nationale contre le cancer; FRM (Fondation de Recherche Medicale)Fondation pour la Recherche Medicale; ARC (Association pour la Recherche sur le Cancer)Fondation ARC pour la Recherche sur le Cancer; Region Nord/Pas-de-CalaisRegion Hauts-de-France; National Academy of Sciences of Ukraine; State Fund for Fundamental Research, UkraineState Fund for Fundamental Research (SFFR) [F46.2/001]; Universite de Lille1	The research of N Prevarskaya and R Skryma is supported by grants from Inserm (Institut National de la Sante et de la Recherche Medicale), Ligue Nationale Contre le Cancer, FRM (Fondation de Recherche Medicale), ARC (Association pour la Recherche sur le Cancer) and Region Nord/Pas-de-Calais. The research of Y Shuba is supported by the National Academy of Sciences of Ukraine and F46.2/001 grant from State Fund for Fundamental Research, Ukraine. Y Shuba is also supported by the visiting scientist program of Universite de Lille1. The authors declare no other conflicts of interest.	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Ther. Targets	MAR	2013	17	3					225	241		10.1517/14728222.2013.741594			17	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	088QW	WOS:000314851700002	23294334				2022-04-25	
J	Xiao, JX; Huang, GQ; Zhang, SH				Xiao, Jun-Xia; Huang, Guo-Qing; Zhang, Sheng-Hua			Soyasaponins inhibit the proliferation of Hela cells by inducing apoptosis	EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY			English	Article						apoptosis; cell cycle; intracellular Ca2+; mitochondrial transmembrane potential; nitric oxide; soyasaponins	COLON-CANCER CELLS; CYTOCHROME-C; NITRIC-OXIDE; INDUCTION; CALCIUM; MACROAUTOPHAGY; MITOCHONDRIA; SAPONINS; EXTRACT; DEATH	This research aimed at investigating the effect of soyasaponins on the proliferation of Hela cells. SS-II, the second fraction of soyasaponins, was separated by column chromatographic method with D101A macroporous resin from soybeans. SS-II could inhibit the proliferation of Hela cells by changing cell cycle distribution and inducing apoptosis. Furthermore, the loss of mitochondrial transmembrane potential was observed by flow cytometry and the increase of intracellular Ca2+ concentration was detected by confocal laser scanning microscope in apoptotic cells. At the same time, the nitric oxide content, nitric oxide synthase (NOS) and inducible NOS activities were also increased. The above results suggested that the inhibitory effect of SS-II on Hela cell proliferation was caused by inducing apoptosis through the mitochondrial pathway. (c) 2007 Elsevier GmbH. All rights reserved.	Huazhong Agr Univ, Sch Food Sci & Technol, Wuhan 430070, Peoples R China; Laiyang Agr Univ, Sch Food Sci & Engn, Qingdao 266109, Peoples R China		Zhang, SH (corresponding author), Huazhong Agr Univ, Sch Food Sci & Technol, Wuhan 430070, Peoples R China.	zhangsh3411@yahoo.com.cn		Huang, Guo-Qing/0000-0002-3343-2008			Brown GC, 2001, BBA-BIOENERGETICS, V1504, P46, DOI 10.1016/S0005-2728(00)00238-3; Ellington AA, 2006, CARCINOGENESIS, V27, P298, DOI 10.1093/carcin/bgi214; Ellington AA, 2005, CARCINOGENESIS, V26, P159, DOI 10.1093/carcin/bgh297; Frankfurt OS, 2003, ANTI-CANCER DRUG, V14, P555, DOI 10.1097/00001813-200308000-00008; Fuzzati N, 1997, J CHROMATOGR A, V777, P233, DOI 10.1016/S0021-9673(97)00157-X; Gu YH, 2005, CANCER LETT, V220, P21, DOI 10.1016/j.canlet.2004.06.037; Gurfinkel DM, 2003, NUTR CANCER, V47, P24, DOI 10.1207/s15327914nc4701_3; Honda H, 2004, ULTRASOUND MED BIOL, V30, P683, DOI 10.1016/j.ultrasmedbio.2004.02.008; Huang Jin, 2004, Acta Nutrimenta Sinica, V26, P477; Kim HY, 2004, CANCER LETT, V210, P1, DOI 10.1016/j.canlet.2004.01.009; Kluck RM, 1997, SCIENCE, V275, P1132, DOI 10.1126/science.275.5303.1132; Kroemer G, 1999, BIOCHEM SOC SYMP, V66, P1; Lorenzo HK, 1999, CELL DEATH DIFFER, V6, P516, DOI 10.1038/sj.cdd.4400527; McConkey DJ, 1997, BIOCHEM BIOPH RES CO, V239, P357, DOI 10.1006/bbrc.1997.7409; MING Y, 2000, ACAD PERI CHANGCHUNG, V16, P48; Oh YJ, 2001, NUTR CANCER, V39, P132, DOI 10.1207/S15327914nc391_18; Petit PX, 1997, MOL CELL BIOCHEM, V174, P185, DOI 10.1023/A:1006848205880; RACHMILEWITZ D, 1998, WORLD J GASTROENT S2, V4, P28; RAO AV, 1995, J NUTR, V125, pS717, DOI 10.1093/jn/125.3_Suppl.717S; Reed JC, 2001, TRENDS MOL MED, V7, P314, DOI 10.1016/S1471-4914(01)02026-3; Wink DA, 1998, FREE RADICAL BIO MED, V25, P434, DOI 10.1016/S0891-5849(98)00092-6; Xiao Jun-Xia, 2006, Zhong Yao Cai, V29, P229; Yanamandra N, 2003, CLIN EXP METASTAS, V20, P375, DOI 10.1023/A:1024043104803; Yoneyama K, 2001, J PHARMACOL TOXICOL, V45, P187, DOI 10.1016/S1056-8719(01)00147-2; YU LP, 1992, J NORMAN BETHUNE U M, V18, P333; YU LP, 1996, CHINA ONCOL, V6, P186	26	34	36	2	7	ELSEVIER GMBH, URBAN & FISCHER VERLAG	JENA	OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY	0940-2993	1618-1433		EXP TOXICOL PATHOL	Exp. Toxicol. Pathol.	SEP	2007	59	1					35	42		10.1016/j.etp.2007.02.004			8	Pathology; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Pathology; Toxicology	212PA	WOS:000249608100005	17582751				2022-04-25	
J	Sun, ZW; Zeng, B; Liu, DD; Zhao, QT; Wang, JY; Xing, HR				Sun, Zhiwei; Zeng, Bin; Liu, Doudou; Zhao, Qiting; Wang, Jianyu; Xing, H. Rosie			S100A8 transported by SEC23A inhibits metastatic colonization via autocrine activation of autophagy	CELL DEATH & DISEASE			English	Article							REGULATES AUTOPHAGY; TUMOR PROGRESSION; CANCER; CELLS; PROTEIN; PERSPECTIVE; APOPTOSIS; RELEASE; PATHWAY	Metastasis is the main cause of failure of cancer treatment. Metastatic colonization is regarded the most rate-limiting step of metastasis and is subjected to regulation by a plethora of biological factors and processes. On one hand, regulation of metastatic colonization by autophagy appears to be stage- and context-dependent, whereas mechanistic characterization remains elusive. On the other hand, interactions between the tumor cells and their microenvironment in metastasis have long been appreciated, whether the secretome of tumor cells can effectively reshape the tumor microenvironment has not been elucidated mechanistically. In the present study, we have identified "SEC23A-S1008-BECLIN1-autophagy axis" in the autophagic regulation of metastatic colonization step, a mechanism that tumor cells can exploit autophagy to exert self-restrain for clonogenic proliferation before the favorable tumor microenvironment is established. Specifically, we employed a paired lung-derived oligometastatic cell line (OL) and the homologous polymetastatic cell line (POL) from human melanoma cell line M14 that differ in colonization efficiency. We show that S100A8 transported by SEC23A inhibits metastatic colonization via autocrine activation of autophagy. Furthermore, we verified the clinical relevance of our experimental findings by bioinformatics analysis of the expression of Sec23a and S100A8 and the clinical-pathological associations. We demonstrate that higher Sec23a and Atg5 expression levels appear to be protective factors and favorable diagnostic (TNM staging) and prognostic (overall survival) markers for skin cutaneous melanoma (SKCM) and colon adenocarcinoma (COAD) patients. And we confirm the bioinformatics analysis results with SKCM biopsy samples.	[Sun, Zhiwei; Zeng, Bin; Liu, Doudou; Zhao, Qiting; Wang, Jianyu] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China; [Sun, Zhiwei; Zeng, Bin; Liu, Doudou; Zhao, Qiting; Wang, Jianyu; Xing, H. Rosie] Chongqing Med Univ, Lab Translat Canc Stem Cell Res, Chongqing, Peoples R China; [Xing, H. Rosie] Chongqing Med Univ, State Key Lab Ultrasound Engn Med Cofounded Chong, Chongqing, Peoples R China; [Xing, H. Rosie] Chongqing Med Univ, Minist Sci & Technol, Coll Biomed Engn, Chongqing, Peoples R China		Wang, JY (corresponding author), Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China.; Wang, JY; Xing, HR (corresponding author), Chongqing Med Univ, Lab Translat Canc Stem Cell Res, Chongqing, Peoples R China.; Xing, HR (corresponding author), Chongqing Med Univ, State Key Lab Ultrasound Engn Med Cofounded Chong, Chongqing, Peoples R China.	wjy2003123@163.com; xinglab310@163.com			National Natural Science FundNational Natural Science Foundation of China (NSFC) [81672908]; National Natural Science Youth Fund [81602596]	This work was supported by the National Natural Science Fund (Grant No. 81672908) and the National Natural Science Youth Fund (Grant No. 81602596).	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AUG 6	2020	11	8							650	10.1038/s41419-020-02835-w			13	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	OD4GX	WOS:000579812000001	32811814	gold, Green Published			2022-04-25	
J	Wang, XC; Li, MJ; Hu, MY; Wei, P; Zhu, W				Wang, Xingchun; Li, Minjie; Hu, Mengyao; Wei, Ping; Zhu, Wei			BAMBI overexpression together with beta-sitosterol ameliorates NSCLC via inhibiting autophagy and inactivating TGF-beta/Smad2/3 pathway	ONCOLOGY REPORTS			English	Article						non-small cell lung cancer; BAMBI; beta-sitosterol; autophagy; TGF-beta	CELL LUNG-CANCER; TGF-BETA; PSEUDORECEPTOR BAMBI; TUMOR-SUPPRESSOR; CHEMO-RESISTANCE; COLON-CANCER; EXPRESSION; APOPTOSIS; BECLIN1; CONTRIBUTES	Non-small cell lung cancer (NSCLC) has the highest mortality rate among all solid tumors with a poor prognosis. The BMP and activin receptor membrane bound inhibitor (BAMBI) has been identified as a hallmark of NSCLC and beta-sitosterol possesses antitumor potentiality. This study explores the effect of BAMBI overexpression and beta-sitosterol in the context of NSCLC. The results revealed that the transfection of pcDNA-BAMBI and beta-sitosterol treatment significantly reduced the levels of autophagy markers light chain 3 (LC3) II and Beclin 1, whereas the levels of LC3 I and p62 were promoted. The reduced punctate accumulations of GFP-LC3 were detected in pcDNA-BAMBI and beta-sitosterol groups, especially in pcDNA-BAMBI + beta-sitosterol group. BAMBI overexpression and beta-sitosterol induced G0/G1 cell cycle arrest and inhibted cell proliferation in A549 cells. In addition, the levels of transforming growth factor-beta (TGF-beta)/p-Smad2/3/c-Myc pathway proteins were decreased. The TGF-beta overexpression further confirmed that BAMBI overexpression and beta-sitosterol treatment suppressed autohagy and viability of A549 cells was through TGF-beta/Smad2/3/c-Myc pathway. Finally, the tumor growth was suppressed in NSCLC xenografts, and the inhibitory effect was stronger under treatment of pcDNA-BAMBI together with beta-sitosterol. These results indicate that BAMBI overexpression and beta-sitosterol may serve as novel targets for the treatment of NSCLC.	[Wang, Xingchun; Hu, Mengyao; Wei, Ping; Zhu, Wei] Canc Hosp Linyi, Dept Internal Med 1, 6 East St Cemetery, Linyi 276001, Shandong, Peoples R China; [Li, Minjie] Canc Hosp Linyi, Dept Internal Med 3, Linyi 276001, Shandong, Peoples R China		Zhu, W (corresponding author), Canc Hosp Linyi, Dept Internal Med 1, 6 East St Cemetery, Linyi 276001, Shandong, Peoples R China.	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Rep.	MAY	2017	37	5					3046	3054		10.3892/or.2017.5508			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	ET9LR	WOS:000400629500058	28440452	Bronze			2022-04-25	
J	Lei, Y; Lui, VWY; Grandis, JR; Egloff, AM				Lei, Yu; Lui, Vivian W. Y.; Grandis, Jennifer R.; Egloff, Ann Marie			Identification of Mutations in the PYRIN-Containing NLR Genes (NLRP) in Head and Neck Squamous Cell Carcinoma	PLOS ONE			English	Article							COLON INFLAMMATION; I INTERFERON; INFLAMMASOMES; AUTOPHAGY; CYTOKINES; PROTEIN; DISEASE; TUFM	Head and Neck Squamous Cell Carcinoma (HNSCC) encompasses malignancies that arise in the mucosa of the upper aerodigestive tract. Recent high throughput DNA sequencing revealed HNSCC genes mutations that contribute to several cancer cell characteristics, including dysregulation of cell proliferation and death, intracellular proinflammatory signaling, and autophagy. The PYRIN-domain containing NLR (Nucleotide-binding domain, Leucine rich Repeats - containing) proteins have recently emerged as pivotal modulators of cell death, autophagy, inflammation, and metabolism. Their close physiologic association with cancer development prompted us to determine whether mutations within the NLRP (PYRIN-containing NLR) gene family were associated with HNSCC genome instability and their clinicopathologic correlations. Catastrophic mutational events underlie cancer cell genome instability and mark a point-of-no-return in cancer cell development and generation of heterogeneity. The mutation profiles of 62 patients with primary conventional type HNSCC excluding other histologic variants were analyzed. Associations were tested using Fisher's Exact test or Mann-Whitney U test. Mutations in NLRP were associated with elevated genome instability as characterized by higher mutation rates. Clinically, NLRP mutations were more frequently found in HNSCC arising in the floor of mouth (50.0%) in comparison with HNSCC at other head and neck locations (14.8%). These mutations were clustered at the leucine rich repeats region of NLRP proteins, and affected NLRP genes were mostly localized at chromosomes 11p15.4 and 19q13.42-19q13.43. Twenty novel NLRP mutations were identified in HNSCC, and mutations in this group of genes were correlated with increased cancer cell genome mutation rates, and such features could be a potential molecular biomarker of HNSCC genome instability.	[Lei, Yu] Univ Pittsburgh, Sch Dent Med, Dept Diagnost Sci, Pittsburgh, PA 15213 USA; [Lui, Vivian W. Y.; Grandis, Jennifer R.; Egloff, Ann Marie] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA USA; [Lui, Vivian W. Y.; Grandis, Jennifer R.; Egloff, Ann Marie] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA; [Grandis, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA; [Egloff, Ann Marie] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA		Lei, Y (corresponding author), Univ Pittsburgh, Sch Dent Med, Dept Diagnost Sci, Pittsburgh, PA 15213 USA.	leiyuleo@gmail.com	Lui, Vivian W. Y./I-5458-2016; Lei, Yu Leo/ABF-1293-2020	Lui, Vivian W. Y./0000-0001-6918-1573; Lei, Yu Leo/0000-0002-9868-9824	Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer neoplasm of the University of Pittsburgh [P50CA097190];  [K07CA137140]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [K07CA137140, P50CA097190] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [R01DE023685] Funding Source: NIH RePORTER	This work was supported by P50CA097190 (JRG) the Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer neoplasm of the University of Pittsburgh and K07CA137140 (AME). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Martin, S; Dudek-Peric, AM; Maes, H; Garg, AD; Gabrysiak, M; Demirsoy, S; Swinnen, JV; Agostinis, P				Martin, S.; Dudek-Peric, A. M.; Maes, H.; Garg, A. D.; Gabrysiak, M.; Demirsoy, S.; Swinnen, J. V.; Agostinis, P.			Concurrent MEK and autophagy inhibition is required to restore cell death associated danger-signalling in Vemurafenib-resistant melanoma cells	BIOCHEMICAL PHARMACOLOGY			English	Article						Melanoma; PLX4032; Danger-signalling; Cell death; Autophagy	ONCOGENIC B-RAF; BRAF INHIBITORS; TUMOR-CELLS; CALRETICULIN EXPOSURE; ANTIMELANOMA ACTIVITY; METASTATIC MELANOMA; ACQUIRED-RESISTANCE; IMPROVED SURVIVAL; CANCER-THERAPY; COLON-CANCER	Vemurafenib (PLX4032), an inhibitor of BRAF(V600E), has demonstrated significant clinical anti-melanoma effects. However, the majority of treated patients develop resistance, due to a variety of molecular mechanisms including MAPK reactivation through MEK. The induction of a cancer cell death modality associated with danger-signalling resulting in surface mobilization of crucial damage-associated-molecular-patterns (DAMPs), e.g. calreticulin (CRT) and heat shock protein-90 (HSP90), from dying cells, is emerging to be crucial for therapeutic success. Both cell death and danger-signalling are modulated by autophagy, a key adaptation mechanism stimulated during melanoma progression. However, whether melanoma cell death induced by MAPK inhibition is associated with danger-signalling, and the reliance of these mechanisms on autophagy, has not yet been scrutinized. Using a panel of isogenic PLX4032-sensitive and resistant melanoma cell lines we show that PLX4032-induced caspase-dependent cell death and DAMPs exposure in the drug-sensitive cells, but failed to do so in the drug-resistant cells, displaying heightened MEK activation. MEK inhibitor, U0126, treatment sensitized PLX4032-resistant cells to death and re-established their danger-signalling capacity. Only melanoma cells exposing death-induced danger-signals were phagocytosed and induced DC maturation. Although the PLX4032-resistant melanoma cells displayed higher basal and drug-induced autophagy, compromising autophagy, pharmacologically or by ATG5 knockdown, was insufficient to re-establish their PLX4032 sensitivity. Interestingly, autophagy abrogation was particularly efficacious in boosting cell death and ecto-CRT/ecto-HSP90 in PLX4032-resistant cells upon blockage of MEK hyper-activation by U0126. Thus combination of MEK inhibitors with autophagy blockers may represent a novel treatment regime to increase both cell death and danger-signalling in Vemurafenib-resistant metastatic melanoma. (C) 2015 Elsevier Inc. All rights reserved.	[Martin, S.; Dudek-Peric, A. M.; Maes, H.; Garg, A. D.; Gabrysiak, M.; Demirsoy, S.; Agostinis, P.] Univ Leuven KU Leuven, Dept Cellular & Mol Med, Cell Death Res & Therapy Unit, B-3000 Leuven, Belgium; [Swinnen, J. V.] Univ Leuven KU Leuven, Dept Oncol, Lab Lipid Metab & Canc, B-3000 Leuven, Belgium		Agostinis, P (corresponding author), Univ Leuven KU Leuven, Dept Cellular & Mol Med, Lab Cell Death Res & Therapy, Campus Gasthuisberg O&N1,Herestr 49,Box 802, B-3000 Leuven, Belgium.	patrizia.agostinis@med.kuleuven.be	Agostinis, Patrizia/ABI-1177-2020; Agostinis, Patrizia/AAO-2468-2020; Swinnen, Johannes V/AAA-2214-2022; Gabrysiak, Magdalena/AAT-2827-2020; Garg, Abhishek D/D-5230-2012	Agostinis, Patrizia/0000-0003-1314-2115; Swinnen, Johannes V/0000-0002-7720-5077; Garg, Abhishek D/0000-0002-9976-9922; demirsoy, seyma/0000-0001-8380-0932; Martin, Seamus/0000-0002-8539-3143	KU LeuvenKU Leuven [GOA/11/2009]; FWOFWO [G0584.12]; Vlaamse Liga tegen Kanker (VLK); Interuniversity Attraction Poles ProgrammeBelgian Federal Science Policy Office [IAP7/32]; Belgian State, Science Policy OfficeBelgian Federal Science Policy Office	We would like to thank Prof. M. Herlyn for the use of the 451-LU and M1617 is ogenic cell lines [10,37,38]. Human immature dendritic cells were kindly provided by Dr Gabriela Bomfim Ferreira. Research was supported by GOA/11/2009 grant of the KU Leuven to P.A. and J.S. and FWO grant G0584.12 to P.A. Aleksandra, M. Dudek-Peric and Hannelore Maes are supported by fellowships of the Vlaamse Liga tegen Kanker (VLK). Abhishek D. Garg is supported by the FWO Postdoctoral Fellowship. This paper represents research results of the IAP7/32 funded by the Interuniversity Attraction Poles Programme, initiated by the Belgian State, Science Policy Office. We would like to thank Sofie Van Eygen and Angela Napolitano for their technical support.	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Pharmacol.	FEB 1	2015	93	3					290	304		10.1016/j.bcp.2014.12.003			15	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	CB2AP	WOS:000349429400005	25529535	Green Accepted			2022-04-25	
J	Wen, Y; Zhang, ZJ; Huang, YP; Wang, KP; Liu, K; Zou, H; Zhou, JJ; Zou, ZX; Luo, SL; Liu, ZT; Wu, ZC; Chen, W; Xiong, L				Wen, Yu; Zhang, Zi-Jian; Huang, Yun-Peng; Wang, Kun-Peng; Liu, Kai; Zou, Heng; Zhou, Jiang-Jiao; Zou, Zhen-Xing; Luo, Shi-Lin; Liu, Zhong-Tao; Wu, Zheng-Chun; Chen, Wei; Xiong, Li			Application of the Ethyl Acetate Extract of Cichorium as a Potential Photosensitizer in Photodynamic Therapy Induces Apoptosis and Autophagy in Colorectal Cancer Cell Lines via the Protein Kinase R-Like Endoplasmic Reticulum Kinase Pathway	JOURNAL OF BIOMEDICAL NANOTECHNOLOGY			English	Article						Cichorium intybus L.; Colorectal Cancer; Photodynamic Therapy; PERK	STRESS; DEATH; TUMOR	The present study aims to evaluate the effect of the ethyl acetate extract of Cichorium (EAEC) as a novel photosensitizer in photodynamic therapy (PDT) of colorectal carcinoma (CRC) HCT116 and SW620 cells. The absorption and fluorescence spectra of EAEC were measured using a UV-vis spectrophotometer and fluorescence spectrophotometer, respectively. EAEC-induced reactive oxygen species (ROS) production in HCT116 and SW620 cells was detected using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and glutathione/glutathione disulfide (GSH/GSSG). The photo- and dark toxicities of EAEC were estimated using the Cell Counting Kit-8 (CCK-8) assay. Cellular uptake and localization of EAEC were detected by confocal laser fluorescence microscopy. Annexin V-FITC/PI staining, Western blotting and immunofluorescence staining were used to assess apoptosis and autophagy. The antitumor activity of EAEC was confirmed in a xenograft model. Finally, effects on the PERK pathway were verified using qRT-PCR and Western blotting. EAEC displayed absorption and fluorescence emission peaks at 660 nm and 678 nm, respectively. EAEC induced ROS production in CRC cells. Assessment of dark toxicity showed that treatment with EAEC alone induced little cytotoxicity in CRC or normal cells but that EAEC-PDT induced significant photocytotoxicity in CRC cells in a time- and dose-dependent manner. After cellular uptake, EAEC was located in the mitochondria. Treatment with EAEC-PDT reduced xenograft tumor size. Further evaluation suggested that activation of the PERK pathway mediates these effects, as the apoptotic rate and autophagy flux increased markedly after EAEC-PDT. EAEC, a natural photosensitizer extracted from Cichorium, displays potential utility in PDT of CRC by targeting the PERK pathway.	[Wen, Yu; Zhang, Zi-Jian; Huang, Yun-Peng; Wang, Kun-Peng; Liu, Kai; Zou, Heng; Zhou, Jiang-Jiao; Liu, Zhong-Tao; Wu, Zheng-Chun; Xiong, Li] Cent S Univ, Xiangya Hosp 2, Dept Gen Surg, Changsha 410011, Hunan, Peoples R China; [Zou, Zhen-Xing] Cent S Univ, Xiangya Sch Pharmaceut Sci, Changsha 410011, Hunan, Peoples R China; [Luo, Shi-Lin] Cent S Univ, Xiangya Hosp 2, Dept Pharm, Changsha 410011, Hunan, Peoples R China; [Chen, Wei] Univ Texas Arlington, Dept Phys, POB 19059, Arlington, TX 76019 USA; [Chen, Wei] Univ Texas Arlington, SAVANT Ctr, Arlington, TX 76019 USA		Xiong, L (corresponding author), Cent S Univ, Xiangya Hosp 2, Dept Gen Surg, Changsha 410011, Hunan, Peoples R China.	lixionghn@csu.edu.cn	wen, yu/AAJ-7482-2021		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81773293]; Hunan Province Natural Science FoundationNatural Science Foundation of Hunan Province [2017DK2011, 2017WK2060, 2017SK0121]	All animal protocols were approved by the Ethical Review Committee of Second Xiangya Hospital of Central South University (the approval number of Ethical Review Committee is SYXK2012-003). The authors declare that they have no competing interests. This work was supported by the National Natural Science Foundation of China (81773293), Hunan Province Natural Science Foundation (2017DK2011, 2017WK2060, 2017SK0121). We thank the Medical Laboratory Center of the Second Xiangya Hospital for providing technical assistance. The confocal microscopy used in this study was performed in the College of Chemistry and Chemical Engineering of Hunan University by Liu Songyang, Chen Yufeng.	Abhishek K, 2018, PLOS NEGLECT TROP D, V12, DOI 10.1371/journal.pntd.0006646; Al-Akhras M. A. 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Biomed. Nanotechnol.	SEP	2019	15	9					1867	1880		10.1166/jbn.2019.2825			14	Nanoscience & Nanotechnology; Materials Science, Biomaterials	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics; Materials Science	IT1YV	WOS:000482645400002	31387675				2022-04-25	
J	Booth, L; Roberts, JL; Poklepovic, A; Dent, P				Booth, Laurence; Roberts, Jane L.; Poklepovic, Andrew; Dent, Paul			PDE5 inhibitors enhance the lethality of [pemetrexed plus sorafenib]	ONCOTARGET			English	Article						sildenafil; autophagy; pemetrexed; chaperone; lung cancer	COLON-CANCER CELLS; NITRIC-OXIDE; TYROSINE NITRATION; ACTIVATION; PATHWAY; PROTEIN; TARGET; PHOSPHODIESTERASES; CYTOTOXICITY; MECHANISM	The combination of pemetrexed and sorafenib has significant clinical activity against a wide variety of tumor types in patients and the present studies were performed to determine whether sildenafil enhances the killing potential of [pemetrexed + sorafenib]. In multiple genetically diverse lung cancer cell lines, sildenafil enhanced the lethality of [pemetrexed + sorafenib]. The three-drug combination reduced the activities of AKT, mTOR and STAT transcription factors; increased the activities of eIF2a and ULK-1; lowered the expression of MCL-1, BCL-XL, thioredoxin and SOD2; and increased the expression of Beclin1. Enhanced cell killing by sildenafil was blocked by inhibition of death receptor signaling and autophagosome formation. Enforced activation of STAT3 and AKT or inhibition of JNK significantly reduced cell killing. The enhanced cell killing caused by sildenafil was more reliant on increased PKG signaling than on the generation of nitric oxide. In vivo sildenafil enhanced the anti-tumor properties of [pemetrexed + sorafenib]. Based on our data we argue that additional clinical studies combining pemetrexed, sorafenib and sildenafil are warranted.	[Booth, Laurence; Roberts, Jane L.; Dent, Paul] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Med Coll Virginia Campus, Richmond, VA 23298 USA; [Poklepovic, Andrew] Virginia Commonwealth Univ, Dept Biochem & Med, Med Coll Virginia Campus, Richmond, VA 23298 USA		Dent, P (corresponding author), Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Med Coll Virginia Campus, Richmond, VA 23298 USA.	pdent@vcu.edu			Massey Cancer Center; NIH-NCI Cancer Center Support GrantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30 CA016059]; Betts family fund;  [PHS R01-CA192613]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA016059, R01CA192613] Funding Source: NIH RePORTER	Support for the present study was funded from philanthropic funding from Massey Cancer Center and PHS R01-CA192613. Services in support of the research project were provided by the VCU Massey Cancer Center Tissue and Data Acquisition and Analysis Core, supported, in part, with funding from NIH-NCI Cancer Center Support Grant P30 CA016059. Thanks to Dr. H.F. Young and the Betts family fund for support in the purchase of the Hermes Wiscan instrument. PD is the holder of the Universal Inc. Chair in Signal Transduction Research. The authors have no conflicts of interest to report.	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J	Luan, F; He, XR; Zeng, N				Luan, Fei; He, Xirui; Zeng, Nan			Tetrandrine: a review of its anticancer potentials, clinical settings, pharmacokinetics and drug delivery systems	JOURNAL OF PHARMACY AND PHARMACOLOGY			English	Review						anticancer; molecular mechanism; natural product; pharmaceutical applications; signalling pathway; tetrandrine	CELL-CYCLE ARREST; MULTIDRUG-RESISTANCE REVERSAL; BIOACTIVE NATURAL-PRODUCTS; COLLAGEN-INDUCED ARTHRITIS; SOLID LIPID NANOPARTICLES; JUN NH2-TERMINAL KINASE; SUPPRESSES TUMOR-GROWTH; PROSTATE-CANCER CELLS; IN-VITRO; INDUCED APOPTOSIS	Objectives Tetrandrine, a natural bisbenzylisoquinoline alkaloid, possesses promising anticancer activities on diverse tumours. This review provides systematically organized information on cancers of tetrandrinein vivoandin vitro, discuss the related molecular mechanisms and put forward some new insights for the future investigations. Key findings Anticancer activities of tetrandrine have been reported comprehensively, including lung cancer, colon cancer, bladder cancer, prostate cancer, ovarian cancer, gastric cancer, breast cancer, pancreatic cancer, cervical cancer and liver cancer. The potential molecular mechanisms corresponding to the anticancer activities of tetrandrine might be related to induce cancer cell apoptosis, autophagy and cell cycle arrest, inhibit cell proliferation, migration and invasion, ameliorate metastasis and suppress tumour cell growth. Pharmaceutical applications of tetrandrine combined with nanoparticle delivery system including liposomes, microspheres and nanoparticles with better therapeutic efficiency have been designed and applied encapsulate tetrandrine to enhance its stability and efficacy in cancer treatment. Tetrandrine was proven to have definite antitumour activities. However, the safety, bioavailability and pharmacokinetic parameter studies on tetrandrine are very limited in animal models, especially in clinical settings. Our present review on anticancer potentials of tetrandrine would be necessary and highly beneficial for providing guidelines and directions for further research of tetrandrine.	[Luan, Fei; Zeng, Nan] Chengdu Univ Tradit Chinese Med, Coll Pharm, Chengdu 611137, Peoples R China; [He, Xirui] Zunyi Med Univ, Dept Bioengn, Zhuhai Campus, Zhuhai 519041, Peoples R China		Zeng, N (corresponding author), Chengdu Univ Tradit Chinese Med, Coll Pharm, Chengdu 611137, Peoples R China.; He, XR (corresponding author), Zunyi Med Univ, Dept Bioengn, Zhuhai Campus, Zhuhai 519041, Peoples R China.	xiruihe6105194@163.com; zengnan666@aliyun.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81473399]; Xinglin Scholar Research Promotion Project of Chengdu University of Traditional Chinese Medicine [CXTD2018014]	This project was financially supported by the National Natural Science Foundation of China (No. 81473399) and the Xinglin Scholar Research Promotion Project of Chengdu University of Traditional Chinese Medicine (No. CXTD2018014).	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Pharm. Pharmacol.	NOV	2020	72	11					1491	1512		10.1111/jphp.13339		JUL 2020	22	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	NX7TW	WOS:000550756400001	32696989				2022-04-25	
J	Hu, F; Wu, Y; Liu, C; Zhu, YC; Ye, SZ; Xi, Y; Cui, W; Bu, SZ				Hu, Fei; Wu, Yu; Liu, Cheng; Zhu, Yingchao; Ye, Shazhou; Xi, Yang; Cui, Wei; Bu, Shizhong			Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines	ONCOLOGY LETTERS			English	Article						penicillin; colorectal cancer; mitochondrial; autophagy; apoptosis	METASTASIS; MECHANISMS; OUTCOMES; SURGERY; ALLERGY; STAGE; LUNG	Colorectal cancer is a common malignant tumor of the gastrointestinal tract. Currently, the main treatment is surgical resection, which can be combined with other treatments. However, treatment efficacy is poor, and colorectal cancer is prone to relapse and metastasis; thus, identifying an effective anti-cancer drug is an urgent requirement. The present study examined the antagonistic effect of penicillin on cultured colorectal cancer cells and the related mechanism. A MTT assay was used to assess the growth of the colorectal cancer cells treated with penicillin and to determine the optimal drug concentration. The wound healing and Transwell invasion assays were performed to investigate the effect of penicillin on the migration and invasion of the colorectal cancer cells. Live cell mitochondrial energy metabolism analysis was performed to detect changes in mitochondrial energy metabolism of the colorectal cancer cells, while western blot analysis was used to measure the expression of cytochrome c and autophagy-related protein, LC3. RFP-GFP-LC3 lentivirus was used to detect autophagic flux, and autophagosomes were observed using a transmission electron microscope, while flow cytometry was used to analyze the effect of penicillin on cell cycle progression and apoptosis of the colorectal cancer cells. After penicillin treatment, the growth, migration and invasion ability of the colorectal cancer cells were inhibited. The mitochondrial energy metabolism of the cell was impaired, and the basic respiratory capacity, maximum respiratory capacity, respiratory potential, and ATP production were all reduced. The protein expression levels of the autophagy-related proteins, LC3-II/LC3-I increased in a dose- and time-dependent manner. In addition, autophagy flux and the number of autophagosomes increased, and mitochondrial structural damage was observed. The cell cycle was arrested at the G(1) phase, the number of early apoptotic cells increased and the protein expression level of cleaved caspase-3 increased, while penicillin-induced apoptosis was blocked by the autophagy inhibitor 3-MA. In conclusion, penicillin disrupted mitochondrial function and energy metabolism in the colorectal cancer cells, which resulted in the induction of autophagic apoptosis and ultimately the inhibition of cancer cell growth and metastasis.	[Hu, Fei; Wu, Yu; Liu, Cheng; Zhu, Yingchao; Ye, Shazhou; Xi, Yang; Bu, Shizhong] Ningbo Univ, Sch Med, Diabet Res Ctr, 818 Fenghua Rd, Ningbo 315211, Zhejiang, Peoples R China; [Hu, Fei] Wenzhou Med Univ, Cixi Biomed Res Inst, Cixi 315300, Zhejiang, Peoples R China; [Cui, Wei] Lihuili Hosp, Ningbo Med Ctr, Dept Colorectal Surg, 57 XingNing Rd, Ningbo 315211, Zhejiang, Peoples R China		Bu, SZ (corresponding author), Ningbo Univ, Sch Med, Diabet Res Ctr, 818 Fenghua Rd, Ningbo 315211, Zhejiang, Peoples R China.; Cui, W (corresponding author), Lihuili Hosp, Ningbo Med Ctr, Dept Colorectal Surg, 57 XingNing Rd, Ningbo 315211, Zhejiang, Peoples R China.	cuiwei1111@live.cn; bushizhong@nbu.edu.cn			Ningbo Science and Technology Innovation Team Program [2014B82002]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81370165]; Fang Runhua Fund of Hong Kong; K. C. Wong Magna Fund in Ningbo University	This study was supported by Ningbo Science and Technology Innovation Team Program (grant no. 2014B82002), the National Natural Science Foundation of China (grant no. 81370165), the Fang Runhua Fund of Hong Kong and the K. C. Wong Magna Fund in Ningbo University.	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Lett.	OCT	2021	22	4							691	10.3892/ol.2021.12952			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	UA1RQ	WOS:000684943400001	34457046	gold, Green Published			2022-04-25	
J	Tigu, AB; Toma, VA; Mot, AC; Jurj, A; Moldovan, CS; Fischer-Fodor, E; Berindan-Neagoe, I; Parvu, M				Tigu, Adrian Bogdan; Toma, Vlad-Alexandru; Mot, Augustin Catalin; Jurj, Ancuta; Moldovan, Cristian Silviu; Fischer-Fodor, Eva; Berindan-Neagoe, Ioana; Parvu, Marcel			The Synergistic Antitumor Effect of 5-Fluorouracil Combined with Allicin against Lung and Colorectal Carcinoma Cells	MOLECULES			English	Article						allicin; 5-FU; apoptosis; colony; synergistic effect; migration	CANCER-CELLS; IN-VITRO; APOPTOSIS; PHYTOCHEMICALS; MODULATORS; AUTOPHAGY; MIGRATION; DEATH	5-fluorouracil (5-FU) is an anticancer drug used to inhibit the proliferation of many different tumor cells. Since severe events are associated with this compound, its combination with different anticancer drugs or adjuvants would allow the use of a significantly lower dose of 5-FU. In this study, we highlighted that the combination of allicin with 5-FU inhibited the cell migration and proliferation of colorectal and lung cancer cells. 5-FU inhibited cell growth with a similar inhibitory concentration for both normal and tumor cells (similar to 200 mu M), while allicin showed different inhibitory concentrations. With an IC50 of 8.625 mu M, lung cancer cells were the most sensitive to allicin. Compared to 5-FU and allicin single-agent treatments, the co-treatment showed a reduced viability rate, with p < 0.05. The morphological changes were visible on all three cell lines, indicating that the treatment inhibited the proliferation of both normal and tumor cells. We highlighted different cell death mechanisms-apoptosis for lung cancer and a non-apoptotic cell death for colorectal cancer. The synergistic antitumor effect of 5-FU combined with allicin was visible against lung and colorectal carcinoma cells. Better results were obtained when a lower concentration of 5-FU was combined with allicin than the single-agent treatment at IC50.	[Tigu, Adrian Bogdan; Moldovan, Cristian Silviu; Fischer-Fodor, Eva; Berindan-Neagoe, Ioana] Univ Med & Pharm Iuliu Hatieganu, MedFuture Res Ctr Adv Med, Cluj Napoca 400349, Romania; [Tigu, Adrian Bogdan; Toma, Vlad-Alexandru; Parvu, Marcel] Babes Bolyai Univ, Fac Biol & Geol, 42 Republicii St, Cluj Napoca 400015, Romania; [Toma, Vlad-Alexandru] Inst Biol Res Cluj Napoca, Cluj Napoca 400113, Romania; [Toma, Vlad-Alexandru] Natl Inst R&D Isotop & Mol Technol, Dept Mol & Biomol Phys, 67-103 Donat, Cluj Napoca 400293, Romania; [Mot, Augustin Catalin] Babes Bolyai Univ, Dept Chem, Fac Chem & Chem Engn, 11 Arany Janos St, Cluj Napoca 400028, Romania; [Jurj, Ancuta; Moldovan, Cristian Silviu; Berindan-Neagoe, Ioana] Iuliu Hatieganu Univ Med & Pharm, Res Ctr Funct Genom Biomed & Translat Med, Cluj Napoca 400028, Romania; [Fischer-Fodor, Eva] Oncol Inst Prof Dr Ion Chiricuta, Dept Radiobiol & Tumor Biol, Cluj Napoca 400028, Romania; [Berindan-Neagoe, Ioana] Oncol Inst Prof Dr Ion Chiricuta, Dept Funct Genom & Expt Pathol, Cluj Napoca 400028, Romania		Parvu, M (corresponding author), Babes Bolyai Univ, Fac Biol & Geol, 42 Republicii St, Cluj Napoca 400015, Romania.	adrianbogdantigu@gmail.com; vlad.al.toma@gmail.com; gusty_chem@yahoo.com; ancajurj15@gmail.com; moldovan.cristian1994@gmail.com; fischer.eva@iocn.ro; ioana.neagoe@umfcluj.ro; marcel.parvu@ubbcluj.ro	Mot, Augustin C./D-3017-2011; Țigu, Adrian Bogdan/AAI-9446-2020; Fischer-Fodor, Eva/C-4506-2011; Mot, Augustin/AAP-4356-2021; Toma, Vlad-Alexandru/S-1514-2019; Pârvu, Marcel/AAH-9752-2020; Moldovan, Cristian/AAE-2871-2022	Mot, Augustin C./0000-0002-1679-0487; Țigu, Adrian Bogdan/0000-0001-9397-0791; Fischer-Fodor, Eva/0000-0002-0898-0547; Mot, Augustin/0000-0002-1679-0487; Toma, Vlad-Alexandru/0000-0002-1141-2559; Pârvu, Marcel/0000-0002-5892-9280; Moldovan, Cristian/0000-0003-2927-4622	UBB of Cluj-Napoca (Romania) [AGC 30411, AGC 30412, AGC 30413]	This research was funded by UBB of Cluj-Napoca (Romania) by a grant to support competitiveness: Nr. AGC 30411 from 5.02.2020 (https://infocercetare.ubbcluj.ro/Proiecte/Proiecte/Edit?id=14721), Nr. AGC 30412 from 5.02.2020 (https://infocercetare.ubbcluj.ro/Proiecte/Proiecte/Edit?id =14722), and. Nr. AGC 30413 from 2020 (https://infocercetare.ubbcluj.ro/Proiecte/Proiecte/Edit?id=14723).	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J	Wang, CY; Guo, DW; Wang, Q; You, S; Qiao, ZP; Liu, Y; Dai, H; Tang, H				Wang, Chaoyi; Guo, Dunwei; Wang, Qiang; You, Song; Qiao, Zhongpeng; Liu, Yong; Dai, Hang; Tang, Hua			Aliskiren targets multiple systems to alleviate cancer cachexia	ONCOLOGY REPORTS			English	Article						cancer cachexia; aliskiren; renin-angiotensin system; inflammation; oxidative stress	RENIN-ANGIOTENSIN SYSTEM; SKELETAL-MUSCLE; OXIDATIVE STRESS; MURINE MYOTUBES; MOUSE MODEL; MICE; AUTOPHAGY; MECHANISMS; INFLAMMATION; DEGRADATION	To examine the effects of aliskiren, a small-molecule renin inhibitor, on cancer cachexia and to explore the underlying mechanisms. A cancer cachexia model was established by subcutaneously injecting C26 mouse colon carcinoma cells into isogenic BALB/c mice. Aliskiren was administered intragastrically [10 mg/kg body weight (BW)] on day 5 (as a preventive strategy, AP group) or on day 12 (as a therapeutic strategy, AT group) after C26 injection. Mice that received no C26 injection (healthy controls, HC group) or only C26 injection but not aliskiren (cancer, CA group) were used as controls. BW, tumor growth, whole body functions, and survival were monitored daily in half of the mice in each group, whereas serum, tumors, and gastrocnemius muscles were harvested from the other mice after sacrifice on day 20 for further analysis. Aliskiren significantly alleviated multiple cachexia-associated symptoms, including BW loss, tumor burden, muscle wasting, muscular dysfunction, and shortened survival. On the molecular level, aliskiren antagonized cachexia-induced activation of the renin-angiotensin system (RAS), systematic and muscular inflammation, oxidative stress, and autophagy-lysosome as well as ubiquitin-proteasome stimulation. In addition, early administration of aliskiren before cachexia development (AP group) resulted in more robust effects in alleviating cachexia or targeting underlying mechanisms than administration after cachexia development (AT group). Aliskiren exhibited potent anti-cachexia activities. These activities were achieved through the targeting of at least four mechanisms underlying cachexia development: RAS activation, increase in systematic inflammation, upregulation of oxidative stress, and stimulation of autophagy-lysosome pathway (ALP) and ubiquitin-proteasome pathway (UPP).	[Wang, Chaoyi; Guo, Dunwei; Wang, Qiang; You, Song; Qiao, Zhongpeng; Liu, Yong; Dai, Hang; Tang, Hua] Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing 400016, Peoples R China; [Wang, Qiang] Suining Cent Hosp, Dept Gastrointestinal Surg, Suining 629000, Sichuan, Peoples R China		Tang, H (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing 400016, Peoples R China.	tanglihua6969@sina.com					Acharyya S, 2007, CLIN CANCER RES, V13, P1356, DOI 10.1158/1078-0432.CCR-06-2307; Burckart K, 2010, CURR OPIN CLIN NUTR, V13, P410, DOI 10.1097/MCO.0b013e328339fdd2; Carson JA, 2010, EXERC SPORT SCI REV, V38, P168, DOI 10.1097/JES.0b013e3181f44f11; Dalla Libera L, 2001, CIRCULATION, V103, P2195; De Luca A, 2003, J PHARMACOL EXP THER, V304, P453, DOI 10.1124/jpet.102.041343; Deans C, 2005, CURR OPIN CLIN NUTR, V8, P265, DOI 10.1097/01.mco.0000165004.93707.88; Del Fiorentino A, 2010, J RENIN-ANGIO-ALDO S, V11, P243, DOI 10.1177/1470320310379449; Fearon K, 2011, LANCET ONCOL, V12, P489, DOI 10.1016/S1470-2045(10)70218-7; Guo CB, 1996, BRIT J ORAL MAX SURG, V34, P325, DOI 10.1016/S0266-4356(96)90012-1; Ham DJ, 2014, CLIN NUTR, V33, P448, DOI 10.1016/j.clnu.2013.06.013; McClung JM, 2010, AM J PHYSIOL-CELL PH, V298, pC542, DOI 10.1152/ajpcell.00192.2009; Murphy KT, 2013, INT J CANCER, V133, P1234, DOI 10.1002/ijc.28128; Murphy KT, 2012, DIS MODEL MECH, V5, P533, DOI 10.1242/dmm.008839; Neo JH, 2010, BMC CANCER, V10, DOI 10.1186/1471-2407-10-134; Patel RB, 2014, EUR J PHARMACOL, V737, P70, DOI 10.1016/j.ejphar.2014.05.009; Penna F, 2014, CURR OPIN CLIN NUTR, V17, P241, DOI 10.1097/MCO.0000000000000048; Penna F, 2013, AM J PATHOL, V182, P1367, DOI 10.1016/j.ajpath.2012.12.023; Rahman M, 2014, ANTIOXID REDOX SIGN, V20, P443, DOI 10.1089/ars.2013.5410; Ruiz-Ortega M, 2001, CURR OPIN NEPHROL HY, V10, P321, DOI 10.1097/00041552-200105000-00005; Russell ST, 2007, CELL SIGNAL, V19, P1797, DOI 10.1016/j.cellsig.2007.04.003; Russell ST, 2006, CANCER LETT, V231, P290, DOI 10.1016/j.canlet.2005.02.007; Sanders PM, 2005, BRIT J CANCER, V93, P425, DOI 10.1038/sj.bjc.6602725; Schmerbach K, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0015052; Schmittgen TD, 2008, NAT PROTOC, V3, P1101, DOI 10.1038/nprot.2008.73; Sukhanov S, 2011, AM J MED SCI, V342, P143, DOI 10.1097/MAJ.0b013e318222e620; Sun GL, 2009, J NEUROL SCI, V280, P40, DOI 10.1016/j.jns.2009.01.020; Tan BHL, 2008, CURR OPIN CLIN NUTR, V11, P400, DOI 10.1097/MCO.0b013e328300ecc1; TANAKA Y, 1990, CANCER RES, V50, P2290; Tardif N, 2013, AM J CLIN NUTR, V98, P1485, DOI 10.3945/ajcn.113.063859; Thomas CM, 2013, CLIN SCI, V124, P529, DOI 10.1042/CS20120448; Tisdale MJ, 2009, PHYSIOL REV, V89, P381, DOI 10.1152/physrev.00016.2008; Tsoli M, 2013, TRENDS ENDOCRIN MET, V24, P174, DOI 10.1016/j.tem.2012.10.006; Vaughan VC, 2013, J CACHEXIA SARCOPENI, V4, P95, DOI 10.1007/s13539-012-0087-1; Wang Q, 2015, MED ONCOL, V32, DOI 10.1007/s12032-015-0538-6; Wang XNH, 2014, NAT REV NEPHROL, V10, P504, DOI 10.1038/nrneph.2014.112; Weng LQ, 2014, ACTA PHARMACOL SIN, V35, P1005, DOI 10.1038/aps.2014.45; Yuan L, 2015, ONCOL REP, V33, P2261, DOI 10.3892/or.2015.3845; Zhang LP, 2009, J AM SOC NEPHROL, V20, P604, DOI 10.1681/ASN.2008060628; Zhang WB, 2014, J CELL MOL MED, V18, P1247, DOI 10.1111/jcmm.12273	39	10	10	1	5	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1021-335X	1791-2431		ONCOL REP	Oncol. Rep.	NOV	2016	36	5					3014	3022		10.3892/or.2016.5118			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DZ6SR	WOS:000385992700069	27667116	Bronze			2022-04-25	
J	Liu, L; Meng, T; Wang, QS; Jin, HZ; Sun, ZQ; Jin, B; Fang, F; Wang, HJ				Liu, L.; Meng, T.; Wang, Q. S.; Jin, H. Z.; Sun, Z. Q.; Jin, B.; Fang, F.; Wang, H. J.			Association of Beclin-1 and microRNA-30a expression with the severity and treatment response of colorectal cancer	GENETICS AND MOLECULAR RESEARCH			English	Article						Beclin-1; MicroRNA-30a; Colorectal cancer; Autophagy; Apoptosis; Prognosis	AUTOPHAGY-RELATED PROTEIN; ADENOCARCINOMA; TUMORIGENESIS; DEGRADATION; CARCINOMA; INDUCTION; PROGNOSIS; SURVIVAL; GENE	We investigated the associations between Beclin-1 and microRNA-30a (miR-30a) expression and the severity and treatment response in colorectal cancer (CRC). Our sample size consisted of 139 CRC patients who were treated with surgery alone. Immunohistochemistry was used to investigate the expression and prognostic significance of Beclin-1 in CRC, while the weak expression of Beclin-1 in normal tissue was used as the basis for assessing tumors (control group). Real-time reverse transcription-polymerase chain reaction quantified miR-30a levels. The expression levels of Beclin-1 and miR-30a were associated with clinical variables and prognoses. Beclin-1 was expressed more highly in CRC tissues than in controls. This expression was related to gender (P = 0.023), histological grade (P = 0.006), M stage (P = 0.004), tumor node metastasis stage (P = 0.020), vascular invasion, and nodal involvement. Patients with higher Beclin-1 expression levels had higher survival rates (P = 0.08) than patients with lower Beclin-1 expression levels. Beclin-1 was a prognostic indicator (P < 0.05) in a multivariate analysis. Beclin-1 was overexpressed in CRC tissues and was correlated with lower levels of miR-30a (P < 0.05, r = -0. 4189). In conclusion, Beclin-1 was a good prognostic indicator in CRC and was correlated with survival rate. Beclin-1 is important in the growth and metastasis of CRC. Apoptosis in CRC might be due to the increased autophagy induced by decreased levels of miR-30a.	[Liu, L.; Meng, T.; Wang, Q. S.; Jin, H. Z.; Sun, Z. Q.; Jin, B.; Fang, F.; Wang, H. J.] Xinjiang Med Univ, Canc Hosp, Dept Abdomen Surg, Urumqi, Peoples R China		Wang, HJ (corresponding author), Xinjiang Med Univ, Canc Hosp, Dept Abdomen Surg, Urumqi, Peoples R China.	wanghaijing_l@163.com			Cancer Hospital Affiliated to Xinjiang Medical University	Research supported by the Cancer Hospital Affiliated to Xinjiang Medical University.	Ahn CH, 2007, APMIS, V115, P1344, DOI 10.1111/j.1600-0463.2007.00858.x; Aita VM, 1999, GENOMICS, V59, P59, DOI 10.1006/geno.1999.5851; Birgisson H, 2011, BMC CANCER, V11, DOI 10.1186/1471-2407-11-438; Cao Y, 2007, CELL RES, V17, P839, DOI 10.1038/cr.2007.78; Chen YS, 2009, PATHOL ONCOL RES, V15, P487, DOI 10.1007/s12253-008-9143-8; Ding ZB, 2008, CANCER RES, V68, P9167, DOI 10.1158/0008-5472.CAN-08-1573; Dunn William A. Jr., 1994, Trends in Cell Biology, V4, P139, DOI 10.1016/0962-8924(94)90069-8; Geng QR, 2012, PLOS ONE, V7; Haggar Fatima A, 2009, Clin Colon Rectal Surg, V22, P191, DOI 10.1055/s-0029-1242458; Huang L, 2013, PATHOL ONCOL RES, V19, P771, DOI 10.1007/s12253-013-9642-0; Kelley RK, 2011, J NATL COMPR CANC NE, V9, P1293, DOI 10.6004/jnccn.2011.0105; Kihara A, 2001, EMBO REP, V2, P330, DOI 10.1093/embo-reports/kve061; Kim HS, 2011, PATHOL RES PRACT, V207, P247, DOI 10.1016/j.prp.2011.02.007; Klionsky DJ, 2000, SCIENCE, V290, P1717, DOI 10.1126/science.290.5497.1717; Lao VV, 2013, TRANSL ONCOL, V6, P458, DOI 10.1593/tlo.13238; Li BX, 2009, AUTOPHAGY, V5, P303, DOI 10.4161/auto.5.3.7491; Liang XH, 1998, J VIROL, V72, P8586, DOI 10.1128/JVI.72.11.8586-8596.1998; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Lin HX, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0060516; Qu XP, 2003, J CLIN INVEST, V112, P1809, DOI 10.1172/JCI200320039; Roesly HB, 2012, AM J PHYSIOL-GASTR L, V302, pG864, DOI 10.1152/ajpgi.00340.2011; Shin YJ, 2010, ARTHRITIS RES THER, V12, DOI 10.1186/ar2921; Wan XB, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0031989; Xia P, 2013, TUMOR BIOL, V34, P3303, DOI 10.1007/s13277-013-1049-8; Zhu H, 2009, AUTOPHAGY, V5, P816, DOI 10.4161/auto.9064	25	7	9	0	0	FUNPEC-EDITORA	RIBEIRAO PRETO	RUA FLORIANO PEIXOTO 2444, ALTO DA BOA VISTA, RIBEIRAO PRETO, SP 00000, BRAZIL	1676-5680			GENET MOL RES	Genet. Mol. Res.		2016	15	2							15027704	10.4238/gmr.15027704			9	Biochemistry & Molecular Biology; Genetics & Heredity	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Genetics & Heredity	DY1UN	WOS:000384880000010	27173217	Bronze			2022-04-25	
J	Foglietta, F; Canaparo, R; Francovich, A; Arena, F; Civera, S; Cravotto, G; Frairia, R; Serpe, L				Foglietta, Federica; Canaparo, Roberto; Francovich, Andrea; Arena, Francesca; Civera, Stefania; Cravotto, Giancarlo; Frairia, Roberto; Serpe, Loredana			Sonodynamic Treatment as an Innovative Bimodal Anticancer Approach: Shock Wave-mediated Tumor Growth Inhibition in a Syngeneic Breast Cancer Model	DISCOVERY MEDICINE			English	Article							PHOTODYNAMIC THERAPY; SOLID TUMORS; COLON-CANCER; CELLS; ULTRASOUND; APOPTOSIS; MECHANISM; AUTOPHAGY; GENES	Despite the great advances in fighting cancer, many therapies still have serious side effects, thus urging the development of highly selective and safe treatments with a wide range of applicability. Sonodynamic therapy (SDT) is an innovative bimodal anticancer approach in which two normally non-toxic components -- one chemical, a sonosensitizer, and one physical, ultrasound -- selectively combine to cause oxidative damage and subsequent cancer cell death. In this study, we investigate the anticancer effect of SDT using shock waves (SWs) to activate protoporphyrin IX (PpIX) cytotoxicity on a Mat B-III syngeneic rat breast cancer model. The SDT-treated group saw a significant decrease (p<0.001) in magnetic resonance imaging (MRI) tumor size measurements 72 hours after treatment with PpIX precursor 5-aminolevulinic acid (ALA) and SWs. This occurred together with significant increase (p<0.01) in apparent diffusion coefficients between pre- and post-treatment MR tumor maps and strong increase in necrotic and apoptotic histological features 72 hours post-treatment. Moreover, significant HIF1A mRNA expression up-regulation was observed along with the prominent selective cleavage of poly (ADP-ribose) polymerase (PARP) and increased autophagy related protein LC3A/B expression in SDT-treated tumors, as compared to untreated tumors 72 hours post-treatment. Thus, the anticancer effect of SDT can be boosted by SWs, making them a valid technology for furthering investigations into this innovative anticancer approach.	[Foglietta, Federica; Canaparo, Roberto; Civera, Stefania; Cravotto, Giancarlo; Serpe, Loredana] Univ Turin, Dept Drug Sci & Technol, I-10125 Turin, Italy; [Francovich, Andrea] Univ Fribourg, Inst Physiol, CH-1770 Fribourg, Switzerland; [Arena, Francesca] Univ Turin, Ctr Preclin Imaging, I-10010 Colleretto Giacosa, Italy; [Frairia, Roberto] Univ Turin, Dept Med Sci, I-10126 Turin, Italy		Serpe, L (corresponding author), Univ Turin, Dept Drug Sci & Technol, Via Pietro Giuria 13, I-10125 Turin, Italy.	loredana.serpe@unito.it	Cravotto, Giancarlo/AAT-9306-2020; Canaparo, Roberto/I-6431-2019	Canaparo, Roberto/0000-0003-2774-6817; Arena, Francesca/0000-0003-3644-0609; Frairia, Roberto/0000-0001-9453-772X	Italian Ministry of Health; Piemonte Region (grant "Giovani Ricercatori ") [GR-2008-1138087]; Associazione Italiana per la Ricerca sul Cancro (grant "MFAG") [MFAG-13048]	Authors gratefully acknowledge funding from the Italian Ministry of Health and Piemonte Region (grant "Giovani Ricercatori 2008," GR-2008-1138087) and from the Associazione Italiana per la Ricerca sul Cancro (grant "MFAG 2012," MFAG-13048).	Ahmad N, 1998, P NATL ACAD SCI USA, V95, P6977, DOI 10.1073/pnas.95.12.6977; Canaparo R, 2006, ANTICANCER RES, V26, P3337; Canaparo R, 2013, INT J NANOMED, V8, P4247, DOI 10.2147/IJN.S51070; Charles-Edwards Elizabeth M, 2006, Cancer Imaging, V6, P135, DOI 10.1102/1470-7330.2006.0021; Chen HJ, 2014, DRUG DISCOV TODAY, V19, P502, DOI 10.1016/j.drudis.2014.01.010; Collaud Sabine, 2004, Current Medicinal Chemistry - Anti-Cancer Agents, V4, P301, DOI 10.2174/1568011043352984; Costley D, 2015, INT J HYPERTHER, V31, P107, DOI 10.3109/02656736.2014.992484; Cui Q, 2007, BIOL PHARM BULL, V30, P859, DOI 10.1248/bpb.30.859; Frenkel V, 2008, ADV DRUG DELIVER REV, V60, P1193, DOI 10.1016/j.addr.2008.03.007; Gao ZXZ, 2013, CANCER LETT, V335, P93, DOI 10.1016/j.canlet.2013.02.006; Hayashi S, 2009, ANTICANCER RES, V29, P897; Kennedy JE, 2005, NAT REV CANCER, V5, P321, DOI 10.1038/nrc1591; Leighton TG, 2007, PROG BIOPHYS MOL BIO, V93, P3, DOI 10.1016/j.pbiomolbio.2006.07.026; Lukes P, 2015, BIOELECTROCHEMISTRY, V103, P103, DOI 10.1016/j.bioelechem.2014.08.019; Millan-Chiu B, 2014, ULTRASOUND MED BIOL, V40, P1599, DOI 10.1016/j.ultrasmedbio.2014.01.012; Millon SR, 2010, J BIOMED OPT, V15, DOI 10.1117/1.3302811; Misik V, 2000, ANN NY ACAD SCI, V899, P335; Pan XH, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0056679; Rassweiler JJ, 2011, EUR UROL, V59, P784, DOI 10.1016/j.eururo.2011.02.033; Serpe L, 2011, TECHNOL CANCER RES T, V10, P85, DOI 10.7785/tcrt.2012.500182; Song DY, 2014, ONCOTARGETS THER, V7, P1801, DOI 10.2147/OTT.S52426; Steinhauser MO, 2014, SOFT MATTER, V10, P4778, DOI 10.1039/c4sm00407h; Su XM, 2015, INT J BIOCHEM CELL B, V60, P82, DOI 10.1016/j.biocel.2014.12.023; Suslick KS, 2008, ANNU REV PHYS CHEM, V59, P659, DOI 10.1146/annurev.physchem.59.032607.093739; Tabuchi Y, 2008, CANCER LETT, V270, P286, DOI 10.1016/j.canlet.2008.05.018; TACHIBANA K, 1993, CANCER LETT, V72, P195, DOI 10.1016/0304-3835(93)90129-W; Tachibana K, 2008, ULTRASONICS, V48, P253, DOI 10.1016/j.ultras.2008.02.003; Tsuru H, 2012, FREE RADICAL BIO MED, V53, P464, DOI 10.1016/j.freeradbiomed.2012.04.025; UMEMURA S, 1990, JPN J CANCER RES, V81, P962, DOI 10.1111/j.1349-7006.1990.tb02674.x; Urban C, 2013, TRANSL CANCER RES, V2, P292, DOI 10.3978/j.issn.2218-676X.2013.08.05; Uzdensky AB, 2004, BIOCHEM BIOPH RES CO, V322, P452, DOI 10.1016/j.bbrc.2004.07.132; Wachowska M, 2011, MOLECULES, V16, P4140, DOI 10.3390/molecules16054140; Wallace K. B., 1997, FREE RADICAL TOXICOL; Wang HS, 2010, J MAGN RESON IMAGING, V32, P409, DOI 10.1002/jmri.22247; Wang XB, 2013, TOXICOL IN VITRO, V27, P1247, DOI 10.1016/j.tiv.2012.12.023; Wood AKW, 2015, ULTRASOUND MED BIOL, V41, P905, DOI 10.1016/j.ultrasmedbio.2014.11.019	36	19	21	0	10	DISCOVERY MEDICINE	TIMONIUM	10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA	1539-6509	1944-7930		DISCOV MED	Discov. Med.	OCT	2015	20	110					197	205					9	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	CY3LI	WOS:000366310600005	26562473				2022-04-25	
J	Mohamed, MS; Kobayashi, A; Taoka, A; Watanabe-Nakayama, T; Kikuchi, Y; Hazawa, M; Minamoto, T; Fukumori, Y; Kodera, N; Uchihashi, T; Ando, T; Wong, RW				Mohamed, Mahmoud Shaaban; Kobayashi, Akiko; Taoka, Azuma; Watanabe-Nakayama, Takahiro; Kikuchi, Yosuke; Hazawa, Masaharu; Minamoto, Toshinari; Fukumori, Yoshihiro; Kodera, Noriyuki; Uchihashi, Takayuki; Ando, Toshio; Wong, Richard W.			High-Speed Atomic Force Microscopy Reveals Loss of Nuclear Pore Resilience as a Dying Code in Colorectal Cancer Cells	ACS NANO			English	Article						high-speed atomic force microscopy; live cell imaging; nanopore; nuclear pore complex; colon cancer	NUCLEOCYTOPLASMIC TRANSPORT; COMPLEX STRUCTURE; NUCLEOPORIN TPR; AURORA KINASE; LIVE CELLS; PROTEINS; ENVELOPE; DYNAMICS; NANOPARTICLES; VISUALIZATION	Nuclear pore complexes (NPCs) are the sole turnstile implanted in the nuclear envelope (NE), acting as a central nanoregulator of transport between the cytosol and the nucleus. NPCs consist of similar to 30 proteins, termed nucleoporins. About one-third of nucleoporins harbor natively unstructured, intrinsically disordered phenylalanine-glycine strings (FG-Nups), which engage in transport selectivity. Because the barriers insert deeply in the NPC, they are nearly inaccessible. Several in vitro barrier models have been proposed; however, the dynamic FG-Nups protein molecules themselves are imperceptible in vivo. We show here that high-speed atomic force microscopy (HS-AFM) can be used to directly visualize nanotopographical changes of the nuclear pore inner channel in colorectal cancer (CRC) cells. Furthermore, using MLN8237/alisertib, an apoptotic and autophagic inducer currently being tested in relapsed cancer clinical trials, we unveiled the functional loss of nucleoporins, particularly the deformation of the FG-Nups barrier, in dying cancer cells. We propose that the loss of this nanoscopic resilience is an irreversible dying code in cells. These findings not only illuminate the potential application of HS-AFM as an intracellular nanoendoscopy but also might aid in the design of future nuclear targeted nanodrug delivery tailored to the individual patient.	[Mohamed, Mahmoud Shaaban; Kobayashi, Akiko; Hazawa, Masaharu; Wong, Richard W.] Kanazawa Univ, Canc Res Inst, Inst Frontier Sci Initiat, Innovat Integrated Biores Core,Cell Bion Res Unit, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan; [Mohamed, Mahmoud Shaaban; Taoka, Azuma; Watanabe-Nakayama, Takahiro; Kodera, Noriyuki; Uchihashi, Takayuki; Ando, Toshio; Wong, Richard W.] Kanazawa Univ, Canc Res Inst, BioAFM Frontier Res Ctr, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan; [Mohamed, Mahmoud Shaaban; Kobayashi, Akiko; Taoka, Azuma; Kikuchi, Yosuke; Hazawa, Masaharu; Fukumori, Yoshihiro; Wong, Richard W.] Kanazawa Univ, Canc Res Inst, Sch Nat Sci & Technol, Div Nat Syst, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan; [Minamoto, Toshinari] Kanazawa Univ, Canc Res Inst, Div Translat & Clin Oncol, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan		Wong, RW (corresponding author), Kanazawa Univ, Canc Res Inst, Inst Frontier Sci Initiat, Innovat Integrated Biores Core,Cell Bion Res Unit, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan.; Wong, RW (corresponding author), Kanazawa Univ, Canc Res Inst, BioAFM Frontier Res Ctr, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan.; Wong, RW (corresponding author), Kanazawa Univ, Canc Res Inst, Sch Nat Sci & Technol, Div Nat Syst, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan.	rwong@staff.kanazawa-u.ac.jp	Wong, Richard W./E-9155-2011; Fukumori, Yoshihiro/J-2483-2014; Hazawa, M/AAA-2712-2021; Kodera, Noriyuki/AAJ-1797-2020; Taoka, Azuma/C-3795-2015; ANDO, Toshio/E-7054-2015; Uchihashi, Takayuki/D-5209-2011; HAZAWA, Masaharu/A-6520-2016	Kodera, Noriyuki/0000-0003-4880-8423; Taoka, Azuma/0000-0003-2492-7858; ANDO, Toshio/0000-0001-8819-154X; Uchihashi, Takayuki/0000-0002-0263-5312; Wong, Richard/0000-0002-2131-6595	MEXT/JSPSMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [24227005, 24117007, 15H04928]; MEXT JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [17H05874, 17K08655]; Extramural Collaborative Research Grant of Cancer Research Institute, Kanazawa University; Uehara Memorial FoundationUehara Memorial Foundation; Suzuken Memorial Foundation; Asahi Glass Foundation; Kowa Life Science Foundation; Sumitomo Foundation; Mochida Memorial Foundation; Sagawa Foundation; Ichiro Kanehara Foundation; Takeda Science FoundationTakeda Science Foundation (TSF); Grants-in-Aid for Scientific ResearchMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [17K19345] Funding Source: KAKEN	This work was supported by a MEXT/JSPS KAKENHI Grant Number 24227005 (to A.T.); 24117007 (to Y.F.); 15H04928 (to T.M.); and 17H05874, 17K08655 (to R.W.) from MEXT Japan, and by grants from the Extramural Collaborative Research Grant of Cancer Research Institute, Kanazawa University, the Uehara Memorial Foundation, the Suzuken Memorial Foundation, the Asahi Glass Foundation, the Kowa Life Science Foundation, the Sumitomo Foundation, the Mochida Memorial Foundation, the Sagawa Foundation, the Ichiro Kanehara Foundation, and the Takeda Science Foundation (to R.W.). We are grateful to Jan Lammerding for Lamin plasmids. We are especially indebted to Roderick Lim and Bart Hoogenboom for insightful discussions at the 4th Kanazawa Bio-AFM workshop.	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J	Jang, D; Song, J; Park, JW; Yoon, SH; Bae, YS				Jang, Da Eun; Song, Junbin; Park, Jeong-Woo; Yoon, Soo-Hyun; Bae, Young-Seuk			Protein kinase CK2 activates Nrf2 via autophagic degradation of Keap1 and activation of AMPK in human cancer cells	BMB REPORTS			English	Article						AMPK; Antioxidants; CK2; Keap1; Nrf2	REGULATION-MEDIATED SENESCENCE; TRANSCRIPTION FACTOR NRF2; HUMAN COLON-CANCER; DOWN-REGULATION; CELLULAR SENESCENCE; INACTIVATION; ACCUMULATION; MECHANISMS; NUTRIENT; STRESS	Protein kinase CK2 downregulation induces premature senescence in various human cell types via activation of the reactive oxygen species (ROS)-p53-p21(Cip1/)(WAF1) pathway. The transcription factor "nuclear factor erythroid 2-related factor 2 '' (Nrf2) plays an important role in maintaining intracellular redox homeostasis. In this study, Nrf2 overexpression attenuated CK2 downregulation-induced ROS production and senescence markers including SA-beta-gal staining and activation of p53-p21(Cip1/)(WAF1) in human breast (MCF-7) and colon (HCT116) cancer cells. CK2 downregulation reduced the transcription of Nrf2 target genes, such as glutathione S transferase, glutathione peroxidase 2, and glutathione reductase 1. Furthermore, CK2 downregulation destabilized Nrf2 protein via inhibiting autophagic degradation of Kelch-like ECH-associated protein 1 (Keap1). Finally, CK2 downregulation decreased the nuclear import of Nrf2 by deactivating AMP-activated protein kinase (AMPK). Collectively, our data suggest that both Keap1 stabilization and AMPK inactivation are associated with decreased activity of Nrf2 in CK2 downregulation-induced cellular senescence.	[Jang, Da Eun; Song, Junbin; Park, Jeong-Woo; Bae, Young-Seuk] Kyungpook Natl Univ, Sch Life Sci, BK2 Plus KNU Creat BioRes Grp, Daegu 41566, South Korea; [Yoon, Soo-Hyun] Kyungpook Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Daegu 41566, South Korea		Bae, YS (corresponding author), Kyungpook Natl Univ, Sch Life Sci, BK2 Plus KNU Creat BioRes Grp, Daegu 41566, South Korea.	ysbae@knu.ac.kr			Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2019R1A2C1005219]	This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2019R1A2C1005219).	Bokov A, 2004, MECH AGEING DEV, V125, P811, DOI 10.1016/j.mad.2004.07.009; Campisi J, 2013, ANNU REV PHYSIOL, V75, P685, DOI 10.1146/annurev-physiol-030212-183653; Coppe JP, 2010, ANNU REV PATHOL-MECH, V5, P99, DOI 10.1146/annurev-pathol-121808-102144; DIMRI GP, 1995, P NATL ACAD SCI USA, V92, P9363, DOI 10.1073/pnas.92.20.9363; Hardie DG, 2012, NAT REV MOL CELL BIO, V13, P251, DOI 10.1038/nrm3311; Hayes JD, 2010, ANTIOXID REDOX SIGN, V13, P1713, DOI 10.1089/ars.2010.3221; Herbig U, 2006, SCIENCE, V311, P1257, DOI 10.1126/science.1122446; Itoh K, 2010, ANTIOXID REDOX SIGN, V13, P1665, DOI 10.1089/ars.2010.3222; Jeon SM, 2010, FEBS LETT, V584, P3137, DOI 10.1016/j.febslet.2010.05.054; Jeyapalan JC, 2007, MECH AGEING DEV, V128, P36, DOI 10.1016/j.mad.2006.11.008; Joo MS, 2016, MOL CELL BIOL, V36, P1931, DOI 10.1128/MCB.00118-16; Kang JY, 2009, MOL CELLS, V28, P489, DOI 10.1007/s10059-009-0141-9; Komatsu M, 2010, NAT CELL BIOL, V12, P213, DOI 10.1038/ncb2021; Kuilman T, 2010, GENE DEV, V24, P2463, DOI 10.1101/gad.1971610; Kwon SM, 2019, BMB REP, V52, P5, DOI 10.5483/BMBRep.2019.52.1.291; Lau A, 2010, MOL CELL BIOL, V30, P3275, DOI 10.1128/MCB.00248-10; Liou GY, 2010, FREE RADICAL RES, V44, P479, DOI 10.3109/10715761003667554; Narita M, 2003, CELL, V113, P703, DOI 10.1016/S0092-8674(03)00401-X; Park JH, 2017, ONCOTARGET, V8, P36950, DOI 10.18632/oncotarget.16939; Park SY, 2016, BIOCHEM BIOPH RES CO, V478, P18, DOI 10.1016/j.bbrc.2016.07.106; Ryu SW, 2006, FEBS LETT, V580, P988, DOI 10.1016/j.febslet.2006.01.028; Salminen A, 2012, AGEING RES REV, V11, P230, DOI 10.1016/j.arr.2011.12.005; Tebay LE, 2015, FREE RADICAL BIO MED, V88, P108, DOI 10.1016/j.freeradbiomed.2015.06.021	23	6	8	0	1	KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY	SEOUL	KOREA SCIENCE & TECHNOLOGY CENTER, # 801,  635-4 , YEOKSAM-DONG, KANGNAM-KU, SEOUL, 135-703, SOUTH KOREA	1976-6696	1976-670X		BMB REP	BMB Rep.	MAY 31	2020	53	5					272	277		10.5483/BMBRep.2020.53.5.044			6	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	LU4TN	WOS:000537749800006	32317087	Green Published, gold			2022-04-25	
J	Yuan, L; Zhang, X; Cheng, K; Li, LP; Guo, ZM; Zeng, L				Yuan, Li; Zhang, Xiao; Cheng, Kai; Li, Liping; Guo, Zhongming; Zeng, Liang			IRF1 Inhibits Autophagy-Mediated Proliferation of Colorectal Cancer via Targeting ATG13	CANCER INVESTIGATION			English	Article						Colorectal cancer; IRF1; growth; autophagy	ULK1 COMPLEX	IRF1 is a nuclear transcription factor that mediates interferon effects and appears to have anti-tumor activity. To determine the roles of IRF1 in colorectal cancer (CRC), we investigated the effects of IRF1 in CRC cells. We found that IRF1 inhibit cell proliferation and tumor growth. Under starvation conditions, IRF1 enhanced apoptosis and reduced autophagic flux. ATG13, an important factor of autophagy complex, was confirmed as a target of IRF1. These findings indicated that IRF1 function as a tumor suppressor in CRC and inhibit autophagy through ATG13, targeting this pathway may provide new insights into the molecular mechanisms of CRC progression.	[Yuan, Li; Cheng, Kai; Li, Liping; Guo, Zhongming; Zeng, Liang] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Pathol, 9 Jinsui Rd, Guangzhou 510623, Peoples R China; [Zhang, Xiao] Guangzhou Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Guangzhou, Peoples R China		Yuan, L (corresponding author), Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Pathol, 9 Jinsui Rd, Guangzhou 510623, Peoples R China.	lizzyklarck@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81802346]; Guangzhou Women and Children's Medical Center/Guangzhou Institute of Pediatrics	This work is supported by the National Natural Science Foundation of China [No. 81802346], and the fund from Guangzhou Women and Children's Medical Center/Guangzhou Institute of Pediatrics [No. YIP-2018-004].	Choo A, 2006, CURR GENE THER, V6, P543, DOI 10.2174/156652306778520683; Condon KJ, 2019, J CELL SCI, V132, DOI 10.1242/jcs.222570; Feng H, 2021, PLOS PATHOG, V17, DOI 10.1371/journal.ppat.1009220; Franke AJ, 2019, JNCI-J NATL CANCER I, V111, P1131, DOI 10.1093/jnci/djz093; Hong M, 2019, CANCER MANAG RES, V11, P369, DOI 10.2147/CMAR.S186236; Huang JB, 2019, CANCER LETT, V459, P86, DOI 10.1016/j.canlet.2019.05.038; Karki R, 2020, JCI INSIGHT, V5, DOI 10.1172/jci.insight.136720; Kimmelman AC, 2017, CELL METAB, V25, P1037, DOI 10.1016/j.cmet.2017.04.004; Li PY, 2012, CANCER LETT, V314, P213, DOI 10.1016/j.canlet.2011.09.031; Liang J, 2015, ONCOTARGET, V6, P31479, DOI 10.18632/oncotarget.5491; Liang JY, 2020, CANCER IMMUNOL RES, V8, P952, DOI 10.1158/2326-6066.CIR-19-0159; Lin MG, 2016, CURR OPIN CELL BIOL, V39, P61, DOI 10.1016/j.ceb.2016.02.010; Manz SM, 2021, THER ADV GASTROENTER, V14, DOI 10.1177/17562848211002018; Mattiuzzi C, 2019, ANN TRANSL MED, V7, DOI 10.21037/atm.2019.07.91; Meyer-Schaller N, 2020, ONCOGENE, V39, P4728, DOI 10.1038/s41388-020-1326-0; Schwartz-Roberts JL, 2015, CANCER RES, V75, P1046, DOI 10.1158/0008-5472.CAN-14-1851; Shao LL, 2019, CANCER IMMUNOL RES, V7, P1258, DOI 10.1158/2326-6066.CIR-18-0711; Somerville TDD, 2020, P NATL ACAD SCI USA, V117, P11471, DOI 10.1073/pnas.1921484117; Wang Y, 2019, ADV EXP MED BIOL, V1206, P67, DOI 10.1007/978-981-15-0602-4_3; White E, 2015, CLIN CANCER RES, V21, P5037, DOI 10.1158/1078-0432.CCR-15-0490; Wu YF, 2020, ONCOL LETT, V19, P1759, DOI 10.3892/ol.2020.11289; Yan B, 2020, PLOS ONE, V15, DOI 10.1371/journal.pone.0239119; Yan YH, 2020, CANCER IMMUNOL IMMUN, V69, P1891, DOI 10.1007/s00262-020-02586-9; Yuan JS, 2019, CANCER LETT, V457, P28, DOI 10.1016/j.canlet.2019.05.006; Zachari M, 2017, ESSAYS BIOCHEM, V61, P585, DOI 10.1042/EBC20170021; Zenke K, 2018, IMMUNOL CELL BIOL, V96, P1095, DOI 10.1111/imcb.12185; Zhou YZ, 2019, CELL PROLIFERAT, V52, DOI 10.1111/cpr.12553	27	2	2	3	5	TAYLOR & FRANCIS INC	PHILADELPHIA	530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA	0735-7907	1532-4192		CANCER INVEST	Cancer Invest.	JAN 2	2022	40	1					35	45		10.1080/07357907.2021.1961265		AUG 2021	11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	XZ2YD	WOS:000685816400001	34313498				2022-04-25	
J	Dubey, A; Jeong, YJ; Jo, JH; Woo, S; Kim, DH; Kim, H; Kang, SC; Stang, PJ; Chi, KW				Dubey, Abhishek; Jeong, Yong Joon; Jo, Jae Ho; Woo, Sangkook; Kim, Dong Hwan; Kim, Hyunuk; Kang, Se Chan; Stang, Peter J.; Chi, Ki-Whan			Anticancer Activity and Autophagy Involvement of Self-Assembled Arene-Ruthenium Metallacycles	ORGANOMETALLICS			English	Article							HOLLOW-FIBER ASSAY; CANCER-CELLS; TISSUE TRANSGLUTAMINASE; BIOLOGICAL-ACTIVITY; IN-VIVO; COORDINATION-COMPLEXES; MOLECULAR-RECTANGLES; PANCREATIC-CANCER; DNA-DAMAGE; DRUG	A suite of six metallacycles (16) was generated via coordination-driven self-assembly using the three dicarboxylate-bridged areneRu precursors [Ru-2(mu-eta(4)-OO boolean AND OO)(eta(6)-p-iPrC(6)H4Me)(2)][CF3SO3](2); (OO boolean AND OO = oxalate (A1), 2,5-dihydroxy-1,4-benzoquinonato (dobq) (A2), 5,8-dihydroxy-1,4-naphthoquinonato (donq) (A3); CF3SO3 = triflate) with one of two dipyridyl ligands (L1 and L2). The metallacycles were isolated in excellent yield (8692%) as triflate salts and characterized by proton (H-1) and carbon-13 (C-13) nuclear magnetic resonance (NMR) and electrospray ionizationmass spectrometry (ESI-MS) to confirm their structural assignments. Single-crystal X-ray crystal analysis of 1 revealed that two L1 ligands bridged two A1 acceptors to form a rectangular architecture. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to evaluate the in vitro cytotoxicities relative to two chemotherapeutic agents: namely, cisplatin and doxorubicin. Metallacycles 3 and 6 potently inhibited the growth of HCT-15 human colon and AGS human gastric cancer cells. The hollow fiber (HF) assay was performed to investigate the in vivo antitumor activities of metallacycles 3 and 6. Metallacycle 6 was more effective in inhibiting HCT-15 cells than metallacycle 3 in both in vitro and in vivo studies. Moreover, 3 and 6 induced autophagic activity in HCT-15 cells. These results suggested that the autophagic response elicited by metallacycles 3 and 6 could mediate the anticancer effects observed in human colorectal cancer cells.	[Dubey, Abhishek; Jo, Jae Ho; Woo, Sangkook; Kim, Dong Hwan; Chi, Ki-Whan] Univ Ulsan, Dept Chem, Ulsan 680749, South Korea; [Jeong, Yong Joon; Kang, Se Chan] Gachon Univ, Dept Life Sci, Songnam 461701, South Korea; [Kim, Hyunuk] Korea Inst Energy Res, Energy Mat Lab, Taejon 305343, South Korea; [Stang, Peter J.] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA		Kang, SC (corresponding author), Gachon Univ, Dept Life Sci, Songnam 461701, South Korea.	sckang73@gachon.ac.kr; kwchi@ulsan.ac.kr	Dubey, Abhishek/M-5118-2016; Stang, Peter J./Y-2744-2019	Dubey, Abhishek/0000-0002-8984-8109; chi, ki-whan/0000-0002-7816-801X	Basic Science Research program through the National Research Foundation of Korea [NRF-2013R1A1A2006859]; Priority Research Center Program through the National Research Foundation of Korea [2009-0093818]; National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [GM-57052]; Research and Development Program of the Korea Institute of Energy Research (KIER) [B5-2513]	K.-W.C. gratefully acknowledges the generous financial support of the Basic Science Research program (NRF-2013R1A1A2006859) and the Priority Research Center Program (2009-0093818) through the National Research Foundation of Korea and the X-ray diffraction experiments performed at the Pohang Accelerator Laboratory in Korea. P.J.S. thanks the National Institutes of Health (NIH) for financial support (GM-57052). H.K. thanks the Research and Development Program of the Korea Institute of Energy Research (KIER, B5-2513).	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J	Senichkin, VV; Kopeina, GS; Zamaraev, AV; Lavrik, IN; Zhivotovsky, BD				Senichkin, V. V.; Kopeina, G. S.; Zamaraev, A. V.; Lavrik, I. N.; Zhivotovsky, B. D.			Nutrient Restriction in Combinatory Therapy of Tumors	MOLECULAR BIOLOGY			English	Review						Calorie restriction; chemotherapy; apoptosis; autophagy mechanisms	ACTIVATED PROTEIN-KINASE; PROGRAMMED CELL-DEATH; BCL-2 FAMILY PROTEINS; COLON-CANCER CELLS; CALORIC RESTRICTION; DIETARY RESTRICTION; OXIDATIVE STRESS; MEDIATED CLEAVAGE; GROWTH-HORMONE; BRAIN-TUMOR	The main objective of anticancer treatment is the elimination of degenerated cells by the induction of programmed cell death. Various chemotherapy drugs and radiation are able to activate cell death mechanisms in tumors. However, unfortunately, monotherapy will always be insufficiently effective because of the variety and virulence of tumors, as well as their ability to develop resistance to drugs. Moreover, monotherapy might constrain many negative side effects. Therefore, the combination of different approaches and/or drugs will increase the efficiency of treatment. One such promising approach is the combination of nutrient restriction (NR) and various chemotherapeutic drugs. This approach may not only affect the autophagy but also influence apoptotic cell death. This review is focused on the potential of NR use in anticancer therapy, as well as the molecular mechanisms underlying this approach.	[Senichkin, V. V.; Kopeina, G. S.; Zamaraev, A. V.; Lavrik, I. N.; Zhivotovsky, B. D.] Moscow MV Lomonosov State Univ, Fac Basic Med, Moscow 119991, Russia; [Lavrik, I. N.] Otto Von Guericke Univ, Dept Translat Inflammat Res, D-39120 Magdeburg, Germany; [Zhivotovsky, B. D.] Karolinska Inst, Div Toxicol, Inst Environm Med, S-17177 Stockholm, Sweden		Zhivotovsky, BD (corresponding author), Moscow MV Lomonosov State Univ, Fac Basic Med, Moscow 119991, Russia.; Zhivotovsky, BD (corresponding author), Karolinska Inst, Div Toxicol, Inst Environm Med, S-17177 Stockholm, Sweden.	Boris.Zhivotovsky@ki.se	Zhivotovsky, Boris/A-4346-2014; Kopeina, Gelina/AAD-5713-2022; Zamaraev, Alexey V/O-6268-2017; Lavrik, Inna N/C-1700-2009; Senichkin, Viacheslav V/P-4602-2017	Zhivotovsky, Boris/0000-0002-2238-3482; Lavrik, Inna N/0000-0002-9324-309X; Senichkin, Viacheslav V/0000-0001-6781-8331; Gelina, Kopeina/0000-0002-7143-6923; Zamaraev, Alexey/0000-0003-0509-6323	Russian Science FoundationRussian Science Foundation (RSF) [14-25-00056]; Russian Foundation for Basic ResearchRussian Foundation for Basic Research (RFBR) [14-04-31090 mol_a, 14-04-00699 A, 16-04-00113 A]; Dynasty Foundation	This work was supported by grant from the Russian Science Foundation (14-25-00056). The work in the authors' laboratories is also supported by grants from the Russian Foundation for Basic Research (14-04-31090 mol_a, 14-04-00699 A and 16-04-00113 A) and the Dynasty Foundation. We apologize to those authors whose primary works could not be cited owing to space limitations.	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Biol.	MAY	2016	50	3					362	378		10.1134/S0026893316030109			17	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	DO9XE	WOS:000378140500004					2022-04-25	
J	Cui, H; Yang, S; Jiang, Y; Li, C; Zhao, Y; Shi, Y; Hao, Y; Qian, F; Tang, B; Yu, P				Cui, H.; Yang, S.; Jiang, Y.; Li, C.; Zhao, Y.; Shi, Y.; Hao, Y.; Qian, F.; Tang, B.; Yu, P.			The glycosyltransferase ST6Gal-I is enriched in cancer stem-like cells in colorectal carcinoma and contributes to their chemo-resistance	CLINICAL & TRANSLATIONAL ONCOLOGY			English	Article						Cancer stem cells (CSCs); Colorectal carcinoma (CRC); ST6 beta-galactoside alpha-2,6-sialyltransferase 1 (ST6Gal-I)	BECLIN 1; AUTOPHAGY; CD44; APOPTOSIS; TARGET; 5-FLUOROURACIL; EXPRESSION; PATHWAY	Presence of cancer stem cells (CSCs) contributes to tumor outgrowth, chemo-resistance and relapse in some cancers including colorectal carcinoma (CRC). The current characterization methods of CSCs in CRC only allows enrichment of CSCs but not their purification. Recent reports showed that ST6 beta-galactoside alpha-2,6-sialyltransferase 1 (ST6Gal-I) plays an essential role in protecting tumor cells against harsh environment like oxidative stress and nutrient deprivation. Therefore, whether ST6Gal-I may be highly expressed in CSCs or whether it may enhance resistance of tumor cells to chemotherapy deserves exploration. ST6Gal-I levels were determined in CRC specimens, compared to paired normal colorectal tissue, and examined in CD133+ vs CD133- CRC cells, and CD44+ vs CD44- CRC cells. ST6Gal-I levels and their association with patient survival were examined. In vivo, 2 CRC cell lines Caco-2 and SW48 were transduced with two lentiviruses, one lentivirus carrying a green fluorescent protein reporter and a luciferase reporter under a cytomegalovirus promoter to allow tracing tumor cells by both fluorescence and luciferase activity, and one lentivirus carrying a nuclear red fluorescent protein under the control of ST6Gal-I promoter to allow separation of ST6Gal-I+ vs ST6Gal-I- CRC cells. Tumor sphere formation, resistance to fluorouracil-induced apoptosis, and frequency of tumor formation after serial adoptive transplantation were done on ST6Gal-I+ vs ST6Gal-I- CRC cells. ST6Gal-I levels were significantly upregulated in clinically obtained CRC specimens, compared to paired normal colorectal tissue. Poorer patient survival was detected in ST6Gal-I-high CRC, compared to ST6Gal-I-low subjects. Higher levels of ST6Gal-I were detected in CD133+ CRC cells than CD133- CRC cells, and in CD44+ CRC cells than in CD44- CRC cells. Compared to ST6Gal-I- CRC cells, ST6Gal-I+ CRC cells generated significantly more tumor spheres in culture, were more resistant to fluorouracil-induced apoptosis likely through upregulating cell autophagy, and generated tumor more frequently after serial adoptive transplantation. ST6Gal-I may be highly expressed in the cancer stem-like cells in CRC and enhances cancer cell resistance to chemotherapy.	[Cui, H.; Yang, S.; Jiang, Y.; Li, C.; Zhao, Y.; Shi, Y.; Hao, Y.; Qian, F.; Tang, B.; Yu, P.] Third Mil Med Univ, Southwest Hosp, Dept Gen Surg, 30 Gaotanyanzheng St, Chongqing 400038, Peoples R China; [Cui, H.; Yang, S.; Jiang, Y.; Li, C.; Zhao, Y.; Shi, Y.; Hao, Y.; Qian, F.; Tang, B.; Yu, P.] Third Mil Med Univ, Southwest Hosp, Ctr Minimal Invas Gastrointestinal Surg, 30 Gaotanyanzheng St, Chongqing 400038, Peoples R China		Tang, B; Yu, P (corresponding author), Third Mil Med Univ, Southwest Hosp, Dept Gen Surg, 30 Gaotanyanzheng St, Chongqing 400038, Peoples R China.; Tang, B; Yu, P (corresponding author), Third Mil Med Univ, Southwest Hosp, Ctr Minimal Invas Gastrointestinal Surg, 30 Gaotanyanzheng St, Chongqing 400038, Peoples R China.	taNTbo@sina.cn; yupeiwu01@yeah.net		Yu, Peiwu/0000-0002-4364-3589			Ayinde O, 2017, ONCOTARGET, V8, P20025, DOI 10.18632/oncotarget.15370; Britain CM, 2017, J BIOL CHEM, V292, P4663, DOI 10.1074/jbc.M116.763862; Chen C, 2000, J BIOL CHEM, V275, P13819, DOI 10.1074/jbc.275.18.13819; Chen XX, 2016, ONCOTARGET, V7, P51955, DOI 10.18632/oncotarget.10192; Christie DR, 2008, J OVARIAN RES, V1, DOI 10.1186/1757-2215-1-3; Curtin JC, 2010, ONCOTARGET, V1, P563, DOI 10.18632/oncotarget.191; De Maio G, 2017, ONCOTARGET, V8, P12406, DOI 10.18632/oncotarget.13628; Djavaheri-Mergny M, 2010, ONCOGENE, V29, P1717, DOI 10.1038/onc.2009.519; Du L, 2008, CLIN CANCER RES, V14, P6751, DOI 10.1158/1078-0432.CCR-08-1034; Feng YC, 2015, TRENDS CELL BIOL, V25, P354, DOI 10.1016/j.tcb.2015.02.002; Garza-Trevino EN, 2015, CANCER CELL INT, V15, DOI 10.1186/s12935-015-0163-7; Green DR, 2014, CELL, V157, P65, DOI 10.1016/j.cell.2014.02.049; Humeniuk R, 2009, MOL CANCER THER, V8, P1045, DOI 10.1158/1535-7163.MCT-08-0717; Jiang F, 2016, CLIN EXP PHARMACOL P, V43, P1021, DOI 10.1111/1440-1681.12649; Kang R, 2011, CELL DEATH DIFFER, V18, P571, DOI 10.1038/cdd.2010.191; Kemper K, 2010, ONCOTARGET, V1, P387, DOI 10.18632/oncotarget.173; Lee M, 2012, RADIAT ONCOL, V7, DOI 10.1186/1748-717X-7-47; LU L, 2016, MEDICINE, V95, DOI DOI 10.1097/MD.0000000000005163; O'Brien CA, 2007, NATURE, V445, P106, DOI 10.1038/nature05372; Oldham RAA, 2015, IMMUNOTHERAPY-UK, V7, P271, DOI [10.2217/IMT.14.108, 10.2217/imt.14.108]; Ricci-Vitiani L, 2007, NATURE, V445, P111, DOI 10.1038/nature05384; Saikawa Y, 2010, GASTRIC CANCER, V13, P11, DOI 10.1007/s10120-009-0537-4; Samadani AA, 2015, MED ONCOL, V32, DOI 10.1007/s12032-015-0492-3; Schultz MJ, 2016, CANCER RES, V76, P3978, DOI 10.1158/0008-5472.CAN-15-2834; Schultz MJ, 2013, J OVARIAN RES, V6, DOI 10.1186/1757-2215-6-25; Srimuangwong K, 2012, WORLD J GASTROENTERO, V18, P2383, DOI 10.3748/wjg.v18.i19.2383; Swindall AF, 2013, CANCER RES, V73, P2368, DOI 10.1158/0008-5472.CAN-12-3424; Swindall AF, 2011, J BIOL CHEM, V286, P22982, DOI 10.1074/jbc.M110.211375; Taniguchi H, 2016, CANCER SCI, V107, P1556, DOI 10.1111/cas.13069; Wang T, 2015, ONCOTARGET, V6, P44191, DOI 10.18632/oncotarget.6176; Wei AW, 2016, ONCOTARGET, V7, P65374, DOI 10.18632/oncotarget.11699; Wielenga VJM, 1999, AM J PATHOL, V154, P515, DOI 10.1016/S0002-9440(10)65297-2; Wu YJ, 2009, STEM CELLS DEV, V18, P1127, DOI 10.1089/scd.2008.0338; Yan YM, 2015, STEM CELL TRANSL MED, V4, P1033, DOI 10.5966/sctm.2015-0048; Zeilstra J, 2008, CANCER RES, V68, P3655, DOI 10.1158/0008-5472.CAN-07-2940; Zeuner A, 2014, CELL STEM CELL, V15, P692, DOI 10.1016/j.stem.2014.11.012; Zhang XP, 2016, BMC CANCER, V16, DOI 10.1186/s12885-016-2981-y	37	7	7	1	2	SPRINGER-VERLAG ITALIA SRL	MILAN	VIA DECEMBRIO, 28, MILAN, 20137, ITALY	1699-048X	1699-3055		CLIN TRANSL ONCOL	Clin. Transl. Oncol.	SEP	2018	20	9					1175	1184		10.1007/s12094-018-1840-5			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GR0SM	WOS:000442233000010	29423671				2022-04-25	
J	Sato, K; Tsuchihara, K; Fujii, S; Sugiyama, M; Goya, T; Atomi, Y; Ueno, T; Ochiai, A; Esumi, H				Sato, Kazunori; Tsuchihara, Katsuya; Fujii, Satoshi; Sugiyama, Masanori; Goya, Tomoyuki; Atomi, Yutaka; Ueno, Takashi; Ochiai, Atsushi; Esumi, Hiroyasu			Autophagy is activated in colorectal cancer cells and contributes to the tolerance to nutrient deprivation	CANCER RESEARCH			English	Article							PROTEIN-KINASE; GLUCOSE STARVATION; HYPOXIA; INHIBITION; LC3; TUMORIGENESIS; PROTEOLYSIS; MATURATION; APOPTOSIS; BECLIN-1	Several types of cancer cells, including colorectal cancerderived cell lines' show austerity, the resistance to nutrient starvation, but exactly how cancer cells obtain energy sources under conditions in which their external nutrient supply is extremely limited remains to be clarified. Because autophagy is a catabolic process by which cells supply amino acids from self-digested organelles, cancer cells are likely to use autophagy to obtain amino acids as alternative energy sources. Amino acid deprivation-induced autophagy was assessed in DLD-1 and other colorectal cancer-derived cell lines. The autophagosome-incorporated LC3-II protein level increased after treatment with a combination of atitolysosome inhibitors, which interferes with the consumption of autophagosomes. Autophagosome formation was also morphologically confirmed using ectopically expressed green fluorescent protein-LC3 fusion proteins in DLD-1 and SW480 cells. These data suggest that autophagosomes were actively produced and promptly consumed in colorectal cancer cells under nutrient starvation. Autolysosome inhibitors and 3-methyl adenine, which suppresses autophagosome formation, remarkably enhanced apoptosis under amino acid-deprived and glucosedeprived condition. Similar results were obtained in the cells with decreased ATG7 level by the RNA interference. These data suggest that autophagy is pivotal for the survival of colorectal cancer cells that have acquired austerity. Furthermore, autophagosome formation was seen only in the tumor cells but not in the adjacent noncancerous epithelial cells of colorectal cancer specimens. Taken together, autophagy is activated in colorectal cancers in vitro and in vivo, and autophagy may contribute to the survival of the cancer cells in their microenvironment.	Natl Canc Ctr Hosp E, Canc Physiol Project, Chiba 2778577, Japan; Natl Canc Ctr Hosp E, Res Ctr Innovat Oncol, Div Pathol, Chiba, Japan; Juntendo Univ, Sch Med, Dept Biochem, Tokyo 113, Japan; Kyorin Univ, Sch Med, Dept Surg, Tokyo, Japan		Esumi, H (corresponding author), Natl Canc Ctr Hosp E, Canc Physiol Project, 6-5-1 Kashiwanoha, Chiba 2778577, Japan.	hesumi@east.ncc.go.jp					Aita VM, 1999, GENOMICS, V59, P59, DOI 10.1006/geno.1999.5851; Bampton ETW, 2005, AUTOPHAGY, V1, P23, DOI 10.4161/auto.1.1.1495; Boya P, 2005, MOL CELL BIOL, V25, P1025, DOI 10.1128/MCB.25.3.1025-1040.2005; Crighton D, 2006, CELL, V126, P121, DOI 10.1016/j.cell.2006.05.034; Degenhardt K, 2006, CANCER CELL, V10, P51, DOI 10.1016/j.ccr.2006.06.001; Esumi H, 2002, J BIOL CHEM, V277, P32791, DOI 10.1074/jbc.M112270200; GUNN JM, 1977, NATURE, V266, P58, DOI 10.1038/266058a0; Harris AL, 2002, NAT REV CANCER, V2, P38, DOI 10.1038/nrc704; Izuishi K, 2000, CANCER RES, V60, P6201; Jager S, 2004, J CELL SCI, V117, P4837, DOI 10.1242/jcs.01370; Jain RK, 2003, NAT MED, V9, P685, DOI 10.1038/nm0603-685; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; Kato K, 2002, ONCOGENE, V21, P6082, DOI 10.1038/sj.onc.1205737; Kirkegaard K, 2004, NAT REV MICROBIOL, V2, P301, DOI 10.1038/nrmicro865; KISEN GO, 1993, CARCINOGENESIS, V14, P2501, DOI 10.1093/carcin/14.12.2501; Kitano M, 2004, GUT, V53, P854, DOI 10.1136/gut.2003.029934; Kondo Y, 2005, NAT REV CANCER, V5, P726, DOI 10.1038/nrc1692; Kuma A, 2007, AUTOPHAGY, V3, P323, DOI 10.4161/auto.4012; LEE HK, 1992, ARCH BIOCHEM BIOPHYS, V296, P271, DOI 10.1016/0003-9861(92)90572-E; Levine B, 2004, DEV CELL, V6, P463, DOI 10.1016/S1534-5807(04)00099-1; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Meley D, 2006, J BIOL CHEM, V281, P34870, DOI 10.1074/jbc.M605488200; OgierDenis E, 1996, J BIOL CHEM, V271, P28593, DOI 10.1074/jbc.271.45.28593; Rez G, 1999, CARCINOGENESIS, V20, P1893, DOI 10.1093/carcin/20.10.1893; Shintani T, 2004, SCIENCE, V306, P990, DOI 10.1126/science.1099993; Suzuki A, 2005, J BIOL CHEM, V280, P31557, DOI 10.1074/jbc.M503714200; Suzuki A, 2004, BIOCHEM BIOPH RES CO, V324, P986, DOI 10.1016/j.bbrc.2004.09.145; Suzuki A, 2003, ONCOGENE, V22, P6177, DOI 10.1038/sj.onc.1206899; Tanida I, 2001, J BIOL CHEM, V276, P1701, DOI 10.1074/jbc.C000752200; Tanida I, 2005, AUTOPHAGY, V1, P84, DOI 10.4161/auto.1.2.1697; Vaupel P, 2001, MED ONCOL, V18, P243, DOI 10.1385/MO:18:4:243	31	284	303	0	26	AMER ASSOC CANCER RESEARCH	PHILADELPHIA	615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA	0008-5472			CANCER RES	Cancer Res.	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J	Xie, YD; Zhao, YF; Shi, L; Li, W; Chen, K; Li, M; Chen, X; Zhang, HW; Li, TT; Matsuzawa-Ishimoto, Y; Yao, XM; Shao, DH; Ke, ZF; Li, J; Chen, Y; Zhang, XM; Cui, J; Cui, SZ; Leng, QB; Cadwell, K; Li, XX; Wei, H; Zhang, HB; Li, HB; Xiao, H				Xie, Yadong; Zhao, Yifan; Shi, Lei; Li, Wei; Chen, Kun; Li, Min; Chen, Xia; Zhang, Haiwei; Li, Tiantian; Matsuzawa-Ishimoto, Yu; Yao, Xiaomin; Shao, Dianhui; Ke, Zunfu; Li, Jian; Chen, Yan; Zhang, Xiaoming; Cui, Jun; Cui, Shuzhong; Leng, Qibin; Cadwell, Ken; Li, Xiaoxia; Wei, Hong; Zhang, Haibing; Li, Huabin; Xiao, Hui			Gut epithelial TSC1/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer	JOURNAL OF CLINICAL INVESTIGATION			English	Article							PROGRAMMED NECROSIS; BOWEL-DISEASE; ADAPTER RIPK3; CELL-DEATH; KINASE; HOMEOSTASIS; MTOR; PHOSPHORYLATION; EXPRESSION; AUTOPHAGY	Although Western diet and dysbios is are the most prominent environmental factors associated with inflammatory bowel diseases (Ins), the corresponding host factors and cellular mechanisms remain poorly defined. Here we report that the TSC1/mTOR pathway in the gut epithelium represents a metabolic and innate immune checkpoint for intestinal dysfunction and inflammation. mTOR hyperactivation triggered by Western diet or Tsc1 ablation led to epithelium necroptosis, barrier disruption, and predisposition to dextran sulfate sodium-induced colitis and inflammation-associated colon cancer. Mechanistically, our results uncovered a critical role for TSC1/mTOR in restraining the expression and activation of RIPK3 in the gut epithelium through TRIM11-mediated ubiquitination and autophagy-dependent degradation. Notably, microbiota depletion by antibiotics or gnotobiotics attenuated RIPK3 expression and activation, thereby alleviating epithelial necroptosis and colitis driven by mTOR hyperactivation. mTOR primarily impinged on RIPK3 to potentiate necroptosis induced by TNF and by microbial pathogen-associated molecular patterns (PAMPs), and hyperactive mTOR and aberrant necroptosis were intertwined in human Ins. Together, our data reveal a previously unsuspected link between the Western diet, microbiota, and necroptosis and identify the mTOR/RIPK3/necroptosis axis as a driving force for intestinal inflammation and cancer.	[Xie, Yadong; Zhao, Yifan; Shi, Lei; Li, Wei; Chen, Xia; Li, Tiantian; Shao, Dianhui; Zhang, Xiaoming; Xiao, Hui] Chinese Acad Sci, Ctr Microbes Dev & Hlth, Key Lab Mol Virol & Immunol, Inst Pasteur Shanghai, Shanghai, Peoples R China; [Xie, Yadong; Zhao, Yifan; Shi, Lei; Li, Wei; Chen, Xia; Li, Tiantian; Shao, Dianhui; Zhang, Xiaoming; Xiao, Hui] CAS Ctr Excellence Mol Cell Sci, Shanghai, Peoples R China; [Xie, Yadong; Zhao, Yifan; Shi, Lei; Li, Wei; Chen, Xia; Li, Tiantian; Shao, Dianhui; Zhang, Xiaoming; Xiao, Hui] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai, Peoples R China; [Xie, Yadong; Chen, Kun; Li, Min; Li, Huabin] Fudan Univ, Affiliated Eye Ear Nose & Throat Hosp, Ctr Allerg & Inflammatory Dis, Shanghai, Peoples R China; [Xie, Yadong; Chen, Kun; Li, Min; Li, Huabin] Fudan Univ, Affiliated Eye Ear Nose & Throat Hosp, Dept Otolaryngol Head & Neck Surg, Shanghai, Peoples R China; [Zhang, Haiwei; Chen, Yan; Zhang, Haibing] Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Nutr Metab & Food Safety, Univ Chinese Acad Sci, Shanghai, Peoples R China; [Matsuzawa-Ishimoto, Yu; Yao, Xiaomin; Cadwell, Ken] NYU, Kimmel Ctr Biol & Med, Skirball Inst Biomol Med, Sch Med, New York, NY USA; [Ke, Zunfu; Li, Huabin] Sun Yat Sen Univ, Dept Pathol, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China; [Li, Jian; Wei, Hong] Third Mil Med Univ, Coll Basic Med Sci, Dept Lab Anim Sci, Chongqing, Peoples R China; [Cui, Jun] Sun Yat Sen Univ, Sch Life Sci, Key Lab Gene Engn, State Key Lab Biocontrol,Minist Educ, Guangzhou, Guangdong, Peoples R China; [Cui, Shuzhong; Leng, Qibin] Guangzhou Med Univ, Affiliated Canc Hosp, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China; [Li, Xiaoxia] Cleveland Clin, Lerner Res Inst, Dept Inflammat & Immun, Cleveland, OH 44106 USA		Xiao, H (corresponding author), Inst Pasteur Shanghai, 320 Yueyang Rd, Shanghai 200031, Peoples R China.; Li, HB (corresponding author), Fudan Univ, Affiliated Eye Ear Nose & Throat Hosp, 83 Fenyang Rd, Shanghai 200031, Peoples R China.	allergyli@163.com; huixiao@ips.ac.cn		Xiao, Hui/0000-0001-5304-243X; Cadwell, Ken/0000-0002-5860-0661	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81720108019, 81725004, 91542206, 31470847, 31700784]; Strategic Priority Research Program of the Chinese Academy of SciencesChinese Academy of Sciences [XDB29030302]; Shanghai Municipal Science and Technology Major Project [2019SHZDZX02]; Key development and research project [2016YFA0502100]	This study was supported by the National Natural Science Foundation of China (81720108019, 81725004, 91542206, 31470847, and 31700784), the Key development and research project 2016YFA0502100, the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29030302), and the Shanghai Municipal Science and Technology Major Project (2019SHZDZX02).	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Clin. Invest.	APR 1	2020	130	4					2111	2128		10.1172/JCI133264			18	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	LJ3XK	WOS:000530101000051	31961824	Green Published, Bronze			2022-04-25	
J	Rui, LX; Shu, SY; Jun, WJ; Mo, CZ; Wu, SZ; Min, LS; Yuan, L; Yong, PJ; Cheng, SZ; Sheng, WS; Yao, TZ				Rui, Li Xiao; Shu, Song Yu; Jun, Wu Jing; Mo, Chen Zi; Wu, Sun Zheng; Min, Liu Shu; Yuan, Lin; Yong, Peng Jin; Cheng, Song Zhi; Sheng, Wang Shi; Yao, Tang Ze			The dual induction of apoptosis and autophagy by SZC014, a synthetic oleanolic acid derivative, in gastric cancer cells via NF-kappa B pathway	TUMOR BIOLOGY			English	Article						SZC014; Oleanolic acid derivative; Apoptosis; Autophagy; NF-kappa B pathway; Gastric cancer cells	URSOLIC ACID; CARCINOMA; PROGRESSION; DEATH; COLON; CYCLE	Oleanolic acid (OA) possesses various pharmacological activities, such as antitumor and anti-inflammation; however, its clinical applications are limited by its relatively weak activities and low bioavailability. In this study, we evaluated the cytotoxic activity of seven novel OA derivatives, one of which, SZC014 [2-(pyrrolidine-1-yl) methyl-3-oxo-olean-12-en-28-oic acid], exhibited the strongest antitumor activity; its anticancer effect on gastric cancer cells and action mechanisms were investigated. The viability of OA and seven synthesized derivatives treating gastric cancer cells was detected using tetrazolium (MTT). Among them, SZC014 exhibited the strongest cytotoxic activity against gastric cancer cells (SGC7901, MGC803, and MKN-45). The effect of SZC014 on cell cycle was identified by propidium iodide (PI) staining assay. The cellular apoptosis induced by SZC014 was tested by annexin V/PI. The cellular morphological changes and ultrastructural structures affected by SZC014 were observed and imaged through inverted phase contrast microscope and transmission electron microscopy. Western blotting was performed to explore the expression of proteins associated with apoptosis (caspase 3, caspase 9, Bax, Bcl-2, and Bcl-xL), autophagy (Beclin 1 and ATG 5), and nuclear factor-kappa B (NF-kappa B) signal pathway, respectively. The cytotoxic activities of all the seven synthesized OA derivatives were stronger than that of OA against gastric cancer cells. SZC014 exhibited stronger cytotoxic activity than other OA derivatives, inhibited the proliferation of gastric cancer cells, besides, induced G2/M phase cell cycle arrest in SGC7901 cells. Both apoptosis and autophagy were found simultaneously in SZC014-treated SGC7901 cells. Caspase-dependent apoptosis induced by SZC014 was confirmed to be associated with upregulation of Bax and downregulation of Bcl-2 and Bcl-xL, while upregulation of Beclin 1 and ATG 5 was inferred to be involved in SZC014-induced autophagy. Moreover, treating cells with SZC014 resulted in a decrease in phosphorylation of I kappa B alpha and NF-kappa B/p65 and NF-kappa B/p65 nuclear translocation. The cytotoxic activities of seven OA derivatives were generally stronger than that of OA, among which, SZC014 possessed the most potent anticancer activity in SGC7901 cells and would be a promising chemotherapic agent for the treatment of gastric cancer.	[Rui, Li Xiao; Shu, Song Yu; Jun, Wu Jing; Mo, Chen Zi; Wu, Sun Zheng; Min, Liu Shu; Yuan, Lin; Yong, Peng Jin; Yao, Tang Ze] Dalian Med Univ, Dept Pharmacol, Dalian, Peoples R China; [Cheng, Song Zhi; Sheng, Wang Shi] Dalian Univ Technol, Coll Pharmaceut Sci & Technol, Dalian, Peoples R China		Yao, TZ (corresponding author), Dalian Med Univ, Dept Pharmacol, Dalian, Peoples R China.; Sheng, WS (corresponding author), Dalian Univ Technol, Coll Pharmaceut Sci & Technol, Dalian, Peoples R China.	wangss@dlut.edu.cn; zeyaotang@163.com	Sun, Zhengwu/AAJ-3126-2021		Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [30772601]; University Innovation Team Project Foundation of Education Department of Liaoning Province [LT2013019]	This work was supported by the Natural Science Foundation of China (no. 30772601) and the University Innovation Team Project Foundation of Education Department of Liaoning Province (no. LT2013019).	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APR	2016	37	4					5133	5144		10.1007/s13277-015-4293-2			12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DK4QS	WOS:000374904500095	26547583				2022-04-25	
J	Kaushik, G; Ramalingam, S; Subramaniam, D; Rangarajanb, P; Protti, P; Rammamoorthy, P; Anant, S; Mammen, JMV				Kaushik, Gaurav; Ramalingam, Satish; Subramaniam, Dharmalingam; Rangarajanb, Parthasarthy; Protti, Piero; Rammamoorthy, Prabhu; Anant, Shrikant; Mammen, Joshua M. V.			Honokiol induces cytotoxic and cytostatic effects in malignant melanoma cancer cells	AMERICAN JOURNAL OF SURGERY			English	Article						Melanoma; AKT; Cyclin D1; Cell-cycle arrest; AKT; mTOR; gamma-secretase	TUMOR-INITIATING CELLS; CYCLIN D1; COLON-CANCER; CUTANEOUS MELANOMA; EPITHELIAL-CELLS; KINASE; EXPRESSION; INHIBITORS; COMBINATION; ACTIVATION	BACKGROUND: Melanomas are aggressive neoplasms with limited therapeutic options. Therefore, developing new therapies with low toxicity is of utmost importance. Honokiol is a natural compound that recently has shown promise as an effective anticancer agent. METHODS: The effect of honokiol on melanoma cancer cells was assessed in vitro. Proliferation and physiologic changes were determined using hexosaminidase assay and transmission electron microscopy. Protein expression was assessed by immunoblotting. RESULTS: Honokiol treatment inhibited cell proliferation and induced death. Electron microscopy showed autophagosome formation. Reduced levels of cyclin D1 accompanied cell-cycle arrest. Honokiol also decreased phosphorylation of AKT (known as protein kinase B) and mammalian target of rapamycin, and inhibited gamma-secretase activity by down-regulating the expression of gamma-secretase complex proteins, especially anterior pharynx-defective 1. CONCLUSIONS: Honokiol is highly effective in inhibiting melanoma cancer cells by attenuating AKT/mammalian target of rapamycin and Notch signaling. These studies warrant further clinical evaluation for honokiol alone or with present chemotherapeutic regimens for the treatment of melanomas. (C) 2012 Elsevier Inc. All rights reserved.	[Ramalingam, Satish; Subramaniam, Dharmalingam; Rangarajanb, Parthasarthy; Rammamoorthy, Prabhu; Anant, Shrikant; Mammen, Joshua M. V.] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66103 USA; [Ramalingam, Satish; Subramaniam, Dharmalingam; Rangarajanb, Parthasarthy; Rammamoorthy, Prabhu; Anant, Shrikant; Mammen, Joshua M. V.] Univ Kansas, Ctr Canc, Kansas City, KS 66160 USA; [Kaushik, Gaurav; Protti, Piero; Mammen, Joshua M. V.] Univ Kansas, Med Ctr, Dept Surg, Kansas City, KS 66103 USA		Anant, S (corresponding author), Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66103 USA.	sanant@kumc.edu	Anant, Shrikant/AAF-8020-2020; Ramalingam, Satish/H-1577-2018	Ramalingam, Satish/0000-0002-3076-279X	National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA; Department of Surgery at the University of Kansas Medical Center; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA109269, R01CA135559] Funding Source: NIH RePORTER	Supported by grants from the National Institutes of Health (S.A.) and from the Department of Surgery at the University of Kansas Medical Center (J.M.V.M.).	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J. Surg.	DEC	2012	204	6					868	873		10.1016/j.amjsurg.2012.09.001			6	Surgery	Science Citation Index Expanded (SCI-EXPANDED)	Surgery	060UG	WOS:000312803000012	23231930	Green Accepted			2022-04-25	
J	Liu, YF; Wu, L; Li, K; Liu, FR; Wang, L; Zhang, DL; Zhou, J; Ma, X; Wang, SY; Yang, SY				Liu, Yanfeng; Wu, Lei; Li, Kai; Liu, Fengrui; Wang, Li; Zhang, Dongling; Zhou, Jing; Ma, Xuan; Wang, Shengyu; Yang, Shuanying			Ornithine aminotransferase promoted the proliferation and metastasis of non-small cell lung cancer via upregulation of miR-21	JOURNAL OF CELLULAR PHYSIOLOGY			English	Article						GSK-3; invasion and migration; miR-21; non-small cell lung cancer; ornithine aminotransferase; proliferation	ROS-DEPENDENT APOPTOSIS; COLON-CANCER; DIHYDROTANSHINONE; MECHANISMS; RESISTANCE; CRYPTOTANSHINONE; SENSITIVITY; MUTATIONS; CARCINOMA; AUTOPHAGY	The incidence and mortality of lung cancer ranked the first among all types of cancer in China, and non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounting for 85% of all lung cancers. Given that the survival rate of patients with advanced NSCLC is still poor nowadays, identification of novel therapeutic targets and the development of effective therapies are desired for the treatment of NSCLC in clinics. In this study, we reported the upregulation of ornithine aminotransferase (OAT) in NSCLC cells and clinical tumor samples as well as its association with the advanced TNM stage, metastasis, and poor tumor differentiation of lung cancer. Using different NSCLC cell lines, we demonstrated that OAT promoted the proliferation, invasion, and migration, inhibited the apoptosis, and altered cell cycle of NSCLC cells; besides, the involvement of OAT-miR-21-glycogen synthase kinase-3 signaling in the functional role of OAT in NSCLC was also revealed. Importantly, in the absence of OAT, the growth and metastasis of tumor lung cancer xenograft was significantly suppressed in the nude mice. Based on our findings, OAT may be a potential novel biomarker for the diagnosis and therapeutic outcome monitoring of NSCLC. Inhibition of OAT may also represent a new therapeutic strategy of NSCLC.	[Liu, Yanfeng; Yang, Shuanying] Xi An Jiao Tong Univ, Dept Resp Med, Affiliated Hosp 2, Xian, Shaanxi, Peoples R China; [Liu, Yanfeng; Li, Kai; Liu, Fengrui; Wang, Li; Zhang, Dongling] Xi An Jiao Tong Univ, Dept Emergency, Affiliated Hosp 1, Xian, Shaanxi, Peoples R China; [Wu, Lei] Xi An Jiao Tong Univ, Dept Med Affairs, Affiliated Hosp 1, Xian, Shaanxi, Peoples R China; [Zhou, Jing; Ma, Xuan; Wang, Shengyu] Xi An Jiao Tong Univ, Dept Resp Med, Affiliated Hosp 1, Xian, Shaanxi, Peoples R China		Yang, SY (corresponding author), Xi An Jiao Tong Univ, Dept Resp Med, Affiliated Hosp 2, Xian, Shaanxi, Peoples R China.	yangshuanying66@163.com			Natural Science Basic Research Plan in Shaanxi Province of China [2017JM8094]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81350032, 81672300]	Natural Science Basic Research Plan in Shaanxi Province of China, Grant/Award Number: 2017JM8094; National Natural Science Foundation of China, Grant/Award Numbers: 81350032, 81672300	Chen S, 2016, ONCOTARGET, V7, P27538, DOI 10.18632/oncotarget.8485; Chen WQ, 2016, CA-CANCER J CLIN, V66, P115, DOI 10.3322/caac.21338; Curran WJ, 2011, J NATL CANCER I, V103, P1452, DOI 10.1093/jnci/djr325; Domoto T, 2016, CANCER SCI, V107, P1363, DOI 10.1111/cas.13028; Ginguay A, 2017, BIOLOGY-BASEL, V6, DOI 10.3390/biology6010018; Hamamoto J, 2013, MOL MED REP, V8, P456, DOI 10.3892/mmr.2013.1517; Hu T, 2016, WORLD J GASTROENTERO, V22, P6876, DOI 10.3748/wjg.v22.i30.6876; Hu T, 2015, PHYTOMEDICINE, V22, P536, DOI 10.1016/j.phymed.2015.03.010; Hu T, 2014, PHYTOMEDICINE, V21, P1264, DOI 10.1016/j.phymed.2014.06.013; Inamura K, 2016, J CLIN MED, V5, DOI 10.3390/jcm5030036; Katagiri S, 2014, DOC OPHTHALMOL, V128, P137, DOI 10.1007/s10633-014-9426-1; Katanoda K, 2011, J EPIDEMIOL, V21, P132, DOI 10.2188/jea.JE20100098; Li LF, 2014, INT J MOL MED, V34, P372, DOI 10.3892/ijmm.2014.1786; Llorens-Martin M, 2014, FRONT MOL NEUROSCI, V7, DOI 10.3389/fnmol.2014.00046; MacDonald BT, 2009, DEV CELL, V17, P9, DOI 10.1016/j.devcel.2009.06.016; Markou A, 2016, LUNG CANCER-TARGETS, V7, P19, DOI 10.2147/LCTT.S60341; *NONSM CELL LUNG C, 2000, COCHRANE DB SYST REV, DOI DOI 10.1002/14651858.CD002139; Pao W, 2011, LANCET ONCOL, V12, P175, DOI 10.1016/S1470-2045(10)70087-5; Pongracz J.E, 2017, RESP RES, V18, P1; Stewart DJ, 2014, JNCI-J NATL CANCER I, V106, DOI 10.1093/jnci/djt356; Walz A, 2017, CLIN CANCER RES, V23, P1891, DOI 10.1158/1078-0432.CCR-15-2240; Wang GL, 2007, P NATL ACAD SCI USA, V104, P2068, DOI 10.1073/pnas.0610832104; Wang L, 2013, LIFE SCI, V93, P344, DOI 10.1016/j.lfs.2013.07.007; Wang L, 2016, LIFE SCI, V151, P224, DOI 10.1016/j.lfs.2016.02.083; Wang L, 2015, PHYTOMEDICINE, V22, P1079, DOI 10.1016/j.phymed.2015.08.009; Xu LY, 2014, CANCER GENET-NY, V207, P214, DOI 10.1016/j.cancergen.2014.04.003; Xu ZY, 2017, CHEM-BIOL INTERACT, V273, P48, DOI 10.1016/j.cbi.2017.06.003; Xue XY, 2016, ONCOTARGET, V7, P84508, DOI 10.18632/oncotarget.13022; Zigmond E, 2015, ACS MED CHEM LETT, V6, P840, DOI 10.1021/acsmedchemlett.5b00153	29	10	10	2	15	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0021-9541	1097-4652		J CELL PHYSIOL	J. Cell. Physiol.	AUG	2019	234	8					12828	12838		10.1002/jcp.27939			11	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	HX2SA	WOS:000467240800061	30549035				2022-04-25	
J	Zhang, C; Shi, J; Mao, SY; Xu, YS; Zhang, D; Feng, LY; Zhang, B; Yan, YY; Wang, SC; Pan, JP; Yang, YP; Lin, NM				Zhang, Chong; Shi, Jing; Mao, Shi-ying; Xu, Ya-si; Zhang, Dan; Feng, Lin-yi; Zhang, Bo; Yan, You-you; Wang, Si-cong; Pan, Jian-ping; Yang, You-ping; Lin, Neng-ming			Role of p38 MAPK in enhanced human cancer cells killing by the combination of aspirin and ABT-737	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE			English	Article						aspirin; ABT-737; combination; p38	DOUBLE-EDGED-SWORD; COLORECTAL-CANCER; LUNG-CANCER; IN-VITRO; AUTOPHAGY; APOPTOSIS; MCL-1; RISK; ACTIVATION; MULTIPLE	Regular use of aspirin after diagnosis is associated with longer survival among patients with mutated-PIK3CA colorectal cancer, but not among patients with wild-type PIK3CA cancer. In this study, we showed that clinically achievable concentrations of aspirin and ABT-737 in combination could induce a synergistic growth arrest in several human PIK3CA wild-type cancer cells. In addition, our results also demonstrated that long-term combination treatment with aspirin and ABT-737 could synergistically induce apoptosis both in A549 and H1299 cells. In the meanwhile, short-term aspirin plus ABT-737 combination treatment induced a greater autophagic response than did either drug alone and the combination-induced autophagy switched from a cytoprotective signal to a death-promoting signal. Furthermore, we showed that p38 acted as a switch between two different types of cell death (autophagy and apoptosis) induced by aspirin plus ABT-737. Moreover, the increased anti-cancer efficacy of aspirin combined with ABT-737 was further validated in a human lung cancer A549 xenograft model. We hope that this synergy may contribute to failure of aspirin cancer therapy and ultimately lead to efficacious regimens for cancer therapy.	[Zhang, Chong; Mao, Shi-ying; Feng, Lin-yi; Wang, Si-cong; Pan, Jian-ping; Yang, You-ping] Zhejiang Univ City Coll, Sch Med, Hangzhou 310003, Zhejiang, Peoples R China; [Shi, Jing] Zhejiang Med Coll, Dept Pharm, Hangzhou, Zhejiang, Peoples R China; [Xu, Ya-si; Zhang, Dan; Zhang, Bo; Yan, You-you; Lin, Neng-ming] Hangzhou First Peoples Hosp, Inst Individualized Med, 261 Huansha Rd, Hangzhou 310006, Zhejiang, Peoples R China; [Zhang, Dan; Lin, Neng-ming] Zhejiang Chinese Med Univ, Affiliated Hangzhou Peoples Hosp 1, Hangzhou, Zhejiang, Peoples R China; [Lin, Neng-ming] Zhejiang Canc Hosp, Lab Clin Pharm, Hangzhou, Zhejiang, Peoples R China		Lin, NM (corresponding author), Hangzhou First Peoples Hosp, Inst Individualized Med, 261 Huansha Rd, Hangzhou 310006, Zhejiang, Peoples R China.	lnm1013@163.com	zhang, chong/D-1812-2016		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81272473, 30872325, 81302806]; Zhejiang Provincial Foundation of National Science [LQ12H31001, LY12H16005]; Science Research Foundation of Zhejiang Health Bureau; Ministry of Health [WKJ2012-2-022]; Science Research Foundation of Zhejiang Health Bureau [2012KYA068]; Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents [2010-190-4]; Excellent Young Teacher Project of Education Department of Zhejiang Province [Ij2013015]; Student Research Fund of Zhejiang University City College [X2014562119]; Scientific and Technological Developing Scheme of Hangzhou City [20130633B34, 20130633B33]	The authors gratefully acknowledge financial support from National Natural Science Foundation of China (81272473, 30872325, 81302806), Zhejiang Provincial Foundation of National Science (LQ12H31001, LY12H16005), Science Research Foundation of Zhejiang Health Bureau & the Ministry of Health (WKJ2012-2-022), Science Research Foundation of Zhejiang Health Bureau (2012KYA068), Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents (2010-190-4), Excellent Young Teacher Project of Education Department of Zhejiang Province (Ij2013015), Student Research Fund of Zhejiang University City College (X2014562119), Scientific and Technological Developing Scheme of Hangzhou City (20130633B34, 20130633B33). Chong Zhang, Jing Shi, Shi-ying Mao, Lin-yi Feng and You-ping Yang performed the research; Neng-ming Lin and Jian-ping Pan designed the research study; You-you Yan and Si-cong Wang contributed essential reagents or tools; Bo Zhang, Ya-si Xu and Dan Zhang analysed the data; Chong Zhang and Bo Zhang wrote the paper.	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Cell. Mol. Med.	FEB	2015	19	2					408	417		10.1111/jcmm.12461			10	Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Research & Experimental Medicine	CA7NQ	WOS:000349104500012	25388762	gold, Green Published			2022-04-25	
J	Koustas, E; Karamouzis, MV; Mihailidou, C; Schizas, D; Papavassiliou, AG				Koustas, Evangelos; Karamouzis, Michalis V.; Mihailidou, Chrysovalantou; Schizas, Dimitrios; Papavassiliou, Athanasios G.			Co-targeting of EGFR and autophagy signaling is an emerging treatment strategy in metastatic colorectal cancer	CANCER LETTERS			English	Review						Colorectal cancer; Epidermal growth factor receptor; Autophagy; Endocytosis; Panitumumab; Cetuximab	GROWTH-FACTOR RECEPTOR; ACQUIRED-RESISTANCE; MONOCLONAL-ANTIBODY; NUCLEAR TRANSLOCATION; PREDICTIVE BIOMARKER; CELL-SURVIVAL; RAB GTPASES; CETUXIMAB; PROTEIN; MECHANISMS	The epidermal growth factor receptor (EGFR) and its associated pathway is a critical key regulator of CRC development and progression. The monoclonal antibodies (MoAbs) cetuximab and panitumumab, directed against EGFR, represent a major step forward in the treatment of metastatic colorectal cancer (mCRC), in terms of progression-free survival and overall survival in several clinical trials. However, the activity of anti-EGFR MoAbs appears to be limited to a subset of patients with mCRC. Studies have highlighted that acquired-resistance to anti-EGFR MoAbs biochemically converge into Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways. Recent data also suggest that acquired-resistance to anti-EGFR MoAbs is accompanied by inhibition of EGFR internalization, ubiqutinization, degradation and prolonged down regulation. It is well established that autophagy, a self-cannibalization process, is considered to be associated with resistance to the anti-EGFR MoAbs therapy. Additionally, autophagy induced by anti-EGFR MoAbs acts as a protective response in cancer cells. Thus, inhibition of autophagy after treatment with EGFR MoAbs can result in autophagic cell death. A combination therapy comprising of anti-EGFR MoAbs and autophagy inhibitors would represent a multi-pronged approach that could be evolved into an active therapeutic strategy in mCRC patients. (C) 2017 Elsevier B.V. All rights reserved.	[Koustas, Evangelos; Karamouzis, Michalis V.; Mihailidou, Chrysovalantou; Papavassiliou, Athanasios G.] Univ Athens, Mol Oncol Unit, Dept Biol Chem, Med Sch, Athens 11527, Greece; [Schizas, Dimitrios] Univ Athens, Dept Surg 1, Med Sch, Athens 11527, Greece		Karamouzis, MV; Papavassiliou, AG (corresponding author), Univ Athens, Dept Biol Chem, Med Sch, 75,M Asias St, Athens 11527, Greece.	mkaramouz@med.uoa.gr; papavas@med.uoa.gr	Karamouzis, Michalis/AAD-2860-2020; SCHIZAS, DIMITRIOS/Z-3323-2019; Koustas, Evangelos/ABE-9336-2020				Ahmad G, 2014, INT J BIOCHEM CELL B, V57, P123, DOI 10.1016/j.biocel.2014.10.019; Algars A, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0099590; Aredia Francesca, 2012, Cells, V1, P520, DOI 10.3390/cells1030520; Armaghany Tannaz, 2012, Gastrointest Cancer Res, V5, P19; Bertelsen V, 2014, MEMBRANES, V4, P424, DOI 10.3390/membranes4030424; Brand TM, 2011, CANCER BIOL THER, V11, P777, DOI 10.4161/cbt.11.9.15050; Bronte G, 2015, ONCOTARGET, V6, P24780, DOI 10.18632/oncotarget.4959; 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Yang X, 2015, CELL BIOSCI, V5, DOI 10.1186/s13578-015-0005-2; Yang ZY, 2012, J HEMATOL ONCOL, V5, DOI 10.1186/1756-8722-5-52; Yazdi Mohammad Hossein, 2015, Avicenna Journal of Medical Biotechnology, V7, P134; Zhao B., 2016, ONCOTARGET, V8, P3980, DOI DOI 10.18632/0NC0TARGET.14012	101	41	42	1	38	ELSEVIER IRELAND LTD	CLARE	ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND	0304-3835	1872-7980		CANCER LETT	Cancer Lett.	JUN 28	2017	396						94	102		10.1016/j.canlet.2017.03.023			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EU0QB	WOS:000400715200010	28323034				2022-04-25	
J	Jin, H; Seo, GS; Lee, SH				Jin, Hao; Seo, Geom Seog; Lee, Sung Hee			Isoliquiritigenin-mediated p62/SQSTM1 induction regulates apoptotic potential through attenuation of caspase-8 activation in colorectal cancer cells	EUROPEAN JOURNAL OF PHARMACOLOGY			English	Article						Isoliquiritigenin; Colorectal cancer cell; Apoptosis; p62/SQSTM1; Caspase-8; 5-Fluorouracil	UP-REGULATION; AUTOPHAGY; TUMORIGENESIS; EXPRESSION; LICORICE; SURVIVAL	Isoliquiritigenin (ISL) is a natural flavonoid that exhibits anticancer properties in various carcinoma cell types. However, the precise mechanism responsible for its anticancer activity has not been elucidated fully. In the present study, we examined ISL-mediated apoptotic mechanisms in colorectal cancer (CRC) cells. ISL induced apoptosis in human HCT-116 cells and caused marked induction of p62/SQSTM1 mRNA and protein expression. Similarly, ISL potently inhibited in vivo tumor growth and induced p62/SQSTM1 expression in xenograft tumor tissues. In a p62/SQSTM1 siRNA transfection study, ISL-induced p62/SQSTM1 expression attenuated ISL-mediated apoptosis by reducing caspase-8 activation. ISL potentiated the apoptotic effects of 5-fluorouracil (5-FU) on HCT-116 cells. However, ISL-induced p62/SQSTM1 expression also attenuated the potency of apoptosis induced by the combination of 5-FU and ISL. Our results demonstrate that ISL-induced p62/SQSTM1 upregulation affects ISL-mediated apoptotic potential through attenuation of caspase-8 activation in CRC cells. These findings broaden the understanding of the molecular basis of ISL-mediated apoptosis.	[Jin, Hao; Lee, Sung Hee] Wonkwang Univ, Coll Pharm, Inst Pharmaceut Res & Dev, Jeonbuk 54538, South Korea; [Seo, Geom Seog] Wonkwang Univ, Coll Med, Digest Dis Res Inst, Jeonbuk 54538, South Korea		Lee, SH (corresponding author), Wonkwang Univ, Coll Pharm, 460 Iksandae Ro, Iksan 54538, South Korea.	gsseo@wku.ac.kr			National Research Foundation of Korea (NRF) - Korea government (Ministry of Science, ICT & Future Planning) [2016R1A2B4009121]	This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science, ICT & Future Planning) (2016R1A2B4009121).	Bjorkoy G, 2005, J CELL BIOL, V171, P603, DOI 10.1083/jcb.200507002; Braun AH, 2004, CANCER-AM CANCER SOC, V100, P1558, DOI 10.1002/cncr.20154; Chen HY, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18102025; Chen XY, 2013, MEDIAT INFLAMM, V2013, DOI 10.1155/2013/432623; Healey E, 2013, ANTICANCER RES, V33, P1053; Hsia SM, 2016, HEAD NECK-J SCI SPEC, V38, pE360, DOI 10.1002/hed.24001; Hsu YL, 2004, CLIN EXP PHARMACOL P, V31, P414, DOI 10.1111/j.1440-1681.2004.04016.x; Huang SB, 2013, J BIOL CHEM, V288, P33654, DOI 10.1074/jbc.M113.518134; Jemal A, 2011, CA-CANCER J CLIN, V61, P69, DOI [10.3322/caac.20107, 10.3322/caac.20115]; Jin XY, 2016, ARCH PHARM RES, V39, P1465, DOI 10.1007/s12272-016-0805-x; Jin ZY, 2009, CELL, V137, P721, DOI 10.1016/j.cell.2009.03.015; Jung JI, 2006, BIOFACTORS, V28, P159, DOI 10.1002/biof.5520280302; Jung JI, 2006, J NUTR BIOCHEM, V17, P689, DOI 10.1016/j.jnutbio.2005.11.006; Jung SK, 2014, J BIOL CHEM, V289, P35839, DOI 10.1074/jbc.M114.585513; Lee SH, 2009, INFLAMM RES, V58, P257, DOI 10.1007/s00011-008-8183-6; Ma J, 2008, MOL CANCER THER, V7, P3670, DOI 10.1158/1535-7163.MCT-08-0715; Mathew R, 2009, CELL, V137, P1062, DOI 10.1016/j.cell.2009.03.048; Pan JA, 2011, MOL CELL BIOL, V31, P3158, DOI 10.1128/MCB.05460-11; Rikiishi Hidemi, 2012, Int J Cell Biol, V2012, P317645, DOI 10.1155/2012/317645; Sahani MH, 2014, AUTOPHAGY, V10, P431, DOI 10.4161/auto.27344; Shakibaei M, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0057218; Takahashi T, 2004, CANCER SCI, V95, P448, DOI 10.1111/j.1349-7006.2004.tb03230.x; TAWATA M, 1992, EUR J PHARMACOL, V212, P87, DOI 10.1016/0014-2999(92)90076-G; Trocoli A, 2014, CELL DEATH DIFFER, V21, P1852, DOI 10.1038/cdd.2014.102; Umemura A, 2016, CANCER CELL, V29, P935, DOI 10.1016/j.ccell.2016.04.006; Wang Zhaoxia, 2013, TEXTILE APPAREL ED, V02, P8, DOI DOI 10.1371/J0URNAL.P0NE.0068566; Watanabe Y, 2016, SCI REP-UK, V6, DOI 10.1038/srep23097; White E, 2012, NAT REV CANCER, V12, P401, DOI 10.1038/nrc3262; Wu CH, 2016, ONCOTARGET, V7, P73432, DOI 10.18632/oncotarget.12369; Zhao HX, 2014, TOXICOL APPL PHARM, V279, P311, DOI 10.1016/j.taap.2014.07.001	30	9	11	4	17	ELSEVIER	AMSTERDAM	RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS	0014-2999	1879-0712		EUR J PHARMACOL	Eur. J. Pharmacol.	DEC 15	2018	841						90	97		10.1016/j.ejphar.2018.10.015			8	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	HA5MK	WOS:000450316400011	30339814				2022-04-25	
J	Chang, JZ; Chen, SD; Zheng, H; Zhang, HP				Chang, Jin-Zhe; Chen, Shu-Dong; Zheng, Hui; Zhang, Hua-Ping			Downregulation of transcription factor EB inhibits the growth and metastasis of colorectal carcinomas	EUROPEAN JOURNAL OF INFLAMMATION			English	Article						colorectal carcinoma; metastasis; TFEB; xenograft tumor model	LYSOSOMAL BIOGENESIS; CANCER STATISTICS; MITF/TFE FAMILY; TFEB; AUTOPHAGY	To determine the roles of transcription factor EB (TFEB) in colorectal cancer (CRC), we collected samples of tumor tissues and normal tissues from 40 patients with CRC. The expression of TFEB in these samples was analyzed by using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Furthermore, we explored the expression of TFEB mRNA in CCD-18Co normal cells and HT-29, HCT-8, C2BBe1 cancer cells. HT-29, HCT-8, and C2BBe1 cancer cells were transfected with a TFEB-specific small interference RNA (siRNA) and scrambled siRNA, then the TFEB expression was confirmed by Western blot. The migration and invasion abilities of cells transfected with TFEB-siRNA were examined by transwell method and wound-healing assay. The subsequent effect of TFEB silencing on the tumor growth was also detected in mice xenograft model in vivo. Our study found that TFEB expression was significantly increased (P < 0.05) in colorectal tumor tissues compared with normal tissues. Consistent with TFEB expression in tissues, compared with the normal CCD-18Co cells, TFEB mRNA expression was also significantly augmented in CRC cells. TFEB protein expression was markedly reduced in HT-29, HCT-8, and C2BBe1 cells after TFEB-siRNA transfection. In addition, inhibition of TFEB expression resulted in decrease of cells migration and invasion abilities. In vivo study, compared with the negative control group, the tumor weight, and volume were also reduced after inhibiting the TFEB expression. Our research suggested that TFEB expression is related to the occurrence and development of colorectal adenocarcinoma. The migration and invasion abilities of cancer cells, the weight and volume of tumor were all decreased when inhibiting TFEB expression. Thus, TFEB serves as an important factor in the development of CRC by modulating cancer cell migration and invasion, showing the potential therapeutic target of CRC in clinical.	[Chang, Jin-Zhe] Guangrao Cty Peoples Hosp, Dept Gen Surg, Dongying, Peoples R China; [Chen, Shu-Dong; Zheng, Hui; Zhang, Hua-Ping] Qingdao Univ, Yuhuangding Hosp, 2 Gastrointestinal Surg, 20 Yuhuangding East Rd, Yantai 264000, Peoples R China		Zhang, HP (corresponding author), Qingdao Univ, Yuhuangding Hosp, 2 Gastrointestinal Surg, 20 Yuhuangding East Rd, Yantai 264000, Peoples R China.	zhanghuapinghpp@163.com					Fang LM, 2017, ACTA PHARMACOL SIN, V38, P1305, DOI 10.1038/aps.2017.25; Giatromanolaki Alexandra, 2017, Clin Breast Cancer, V17, pe119, DOI 10.1016/j.clbc.2016.11.006; Giatromanolaki A, 2015, LUNG CANCER, V90, P98, DOI 10.1016/j.lungcan.2015.07.008; Klein K, 2016, INT J ONCOL, V49, P164, DOI 10.3892/ijo.2016.3505; Lilleby Wolfgang, 2015, J Med Case Rep, V9, P281, DOI 10.1186/s13256-015-0749-7; Malouf GG, 2011, J UROLOGY, V185, P24, DOI 10.1016/j.juro.2010.08.092; Martignoni G, 2009, MODERN PATHOL, V22, P1016, DOI 10.1038/modpathol.2009.58; Martina JA, 2014, CELL MOL LIFE SCI, V71, P2483, DOI 10.1007/s00018-014-1565-8; Nabar NR, 2017, YALE J BIOL MED, V90, P301; Napolitano G, 2016, J CELL SCI, V129, P2475, DOI 10.1242/jcs.146365; Neill T, 2017, J BIOL CHEM, V292, P16211, DOI 10.1074/jbc.M116.769950; Parkin DM, 2005, CA-CANCER J CLIN, V55, P74, DOI 10.3322/canjclin.55.2.74; Sakamoto H, 2018, ORAL DIS, V24, P741, DOI 10.1111/odi.12826; Sardiello M, 2009, SCIENCE, V325, P473, DOI 10.1126/science.1174447; Settembre C, 2013, NAT CELL BIOL, V15, P647, DOI 10.1038/ncb2718; Settembre C, 2011, SCIENCE, V332, P1429, DOI 10.1126/science.1204592; Siegel RL, 2017, CA-CANCER J CLIN, V67, P177, DOI 10.3322/caac.21395; Siegel RL, 2017, CA-CANCER J CLIN, V67, P7, DOI 10.3322/caac.21387; Tsuda M, 2007, CANCER RES, V67, P919, DOI 10.1158/0008-5472.CAN-06-2855; Zeng CJ, 2016, GASTROENTEROLOGY, V150, P1633, DOI 10.1053/j.gastro.2016.02.076; Zhang ZL, 2017, BIOMED PHARMACOTHER, V89, P1055, DOI 10.1016/j.biopha.2017.02.103; Zhao Enpeng, 2012, Hepatology, V55, P1632, DOI 10.1002/hep.25619; Zhitomirsky B, 2015, ONCOTARGET, V6, P1143, DOI 10.18632/oncotarget.2732	23	0	0	0	0	SAGE PUBLICATIONS INC	THOUSAND OAKS	2455 TELLER RD, THOUSAND OAKS, CA 91320 USA	1721-727X	2058-7392		EUR J INFLAMM	Eur. J. Inflamm.	OCT 17	2018	16								2058739218805333	10.1177/2058739218805333			9	Immunology	Science Citation Index Expanded (SCI-EXPANDED)	Immunology	HE8ZV	WOS:000453737400001		gold			2022-04-25	
J	Kijima, T; Nakagawa, H; Shimonosono, M; Chandramouleeswaran, PM; Hara, T; Sahu, V; Kasagi, Y; Kikuchi, O; Tanaka, K; Giroux, V; Muir, AB; Whelan, KA; Ohashi, S; Naganuma, S; Klein-Szanto, AJ; Shinden, Y; Sasaki, K; Omoto, I; Kita, Y; Muto, M; Bass, AJ; Diehl, JA; Ginsberg, GG; Doki, Y; Mori, M; Uchikado, Y; Arigami, T; Avadhani, NG; Basu, D; Rustgi, AK; Natsugoe, S				Kijima, Takashi; Nakagawa, Hiroshi; Shimonosono, Masataka; Chandramouleeswaran, Prasanna M.; Hara, Takeo; Sahu, Varun; Kasagi, Yuta; Kikuchi, Osamu; Tanaka, Koji; Giroux, Veronique; Muir, Amanda B.; Whelan, Kelly A.; Ohashi, Shinya; Naganuma, Seiji; Klein-Szanto, Andres J.; Shinden, Yoshiaki; Sasaki, Ken; Omoto, Itaru; Kita, Yoshiaki; Muto, Manabu; Bass, Adam J.; Diehl, J. Alan; Ginsberg, Gregory G.; Doki, Yuichiro; Mori, Masaki; Uchikado, Yasuto; Arigami, Takaaki; Avadhani, Narayan G.; Basu, Devraj; Rustgi, Anil K.; Natsugoe, Shoji			Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells	CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY			English	Article						3D Organoids; Autophagy; CD44; 5-Fluorouracil	CANCER; SURGERY; PROTEIN; MODELS; COLON	We have established 3 dimensional organoids from patients with esophageal and oropharyngeal squamous cell carcinomas. We show that 3-dimensional organoids reveal resistance mechanisms and provide a robust platform to predict therapy response in the setting of personalized medicine. BACKGROUND & AIMS: Oropharyngeal and esophageal squamous cell carcinomas, especially the latter, are a lethal disease, featuring intratumoral cancer cell heterogeneity and therapy resistance. To facilitate cancer therapy in personalized medicine, three-dimensional (3D) organoids may be useful for functional characterization of cancer cells ex vivo. We investigated the feasibility and the utility of patient-derived 3D organoids of esophageal and oropharyngeal squamous cell carcinomas. METHODS: We generated 3D organoids from paired biopsies representing tumors and adjacent normal mucosa from therapy-naive patients and cell lines. We evaluated growth and structures of 3D organoids treated with 5-fluorouracil ex vivo. RESULTS: Tumor-derived 3D organoids were grown successfully from 15 out of 21 patients (71.4%) and passaged with recapitulation of the histopathology of the original tumors. Successful formation of tumor-derived 3D organoids was associated significantly with poor response to presurgical neoadjuvant chemotherapy or chemoradiation therapy in informative patients (P = 0.0357, progressive and stable diseases, n = 10 vs. partial response, n = 6). The 3D organoid formation capability and 5-fluorouracil resistance were accounted for by cancer cells with high CD44 expression and autophagy, respectively. Such cancer cells were found to be enriched in patient-derived 3D organoids surviving 5-fluorouracil treatment. CONCLUSIONS: The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine.	[Kijima, Takashi; Shimonosono, Masataka; Shinden, Yoshiaki; Sasaki, Ken; Omoto, Itaru; Kita, Yoshiaki; Uchikado, Yasuto; Arigami, Takaaki; Natsugoe, Shoji] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Digest Surg Breast & Thyroid Surg, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan; [Kijima, Takashi; Avadhani, Narayan G.] Univ Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA; [Nakagawa, Hiroshi; Shimonosono, Masataka; Chandramouleeswaran, Prasanna M.; Tanaka, Koji; Giroux, Veronique; Whelan, Kelly A.; Ginsberg, Gregory G.; Rustgi, Anil K.] Univ Penn, Perelman Sch Med, Dept Med, Div Gastroenterol, 951 Biomed Res Bldg,421 Curie Blvd, Philadelphia, PA 19104 USA; [Nakagawa, Hiroshi; Shimonosono, Masataka; Chandramouleeswaran, Prasanna M.; Tanaka, Koji; Giroux, Veronique; Whelan, Kelly A.; Ginsberg, Gregory G.; Rustgi, Anil K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA; [Hara, Takeo; Tanaka, Koji; Doki, Yuichiro; Mori, Masaki] Osaka Univ, Grad Sch Med, Dept Gastroenterol Surg, Osaka, Japan; [Sahu, Varun; Basu, Devraj] Univ Penn, Perelman Sch Med, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA; [Kasagi, Yuta; Muir, Amanda B.] Childrens Hosp Philadelphia, Div Pediat Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA; [Kikuchi, Osamu; Ohashi, Shinya; Muto, Manabu] Kyoto Univ, Grad Sch Med, Dept Therapeut Oncol, Kyoto, Japan; [Kikuchi, Osamu; Bass, Adam J.] Harvard Med Sch, Dept Med, Dana Farber Canc Inst, Boston, MA USA; [Whelan, Kelly A.] Temple Univ, Lewis Katz Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19122 USA; [Naganuma, Seiji] Kochi Univ, Dept Pathol, Sch Med, Nankoku, Kochi, Japan; [Klein-Szanto, Andres J.] Fox Chase Canc Ctr, Histopathol Facil & Canc Biol Program, 7701 Burholme Ave, Philadelphia, PA 19111 USA; [Diehl, J. Alan] Med Univ South Carolina, Hollings Canc Ctr, Dept Biochem & Mol Biol, Charleston, SC 29425 USA		Natsugoe, S (corresponding author), Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Digest Surg Breast & Thyroid Surg, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan.; Rustgi, AK (corresponding author), Univ Penn, Perelman Sch Med, Dept Med, Div Gastroenterol, 951 Biomed Res Bldg,421 Curie Blvd, Philadelphia, PA 19104 USA.; Nakagawa, H (corresponding author), Univ Penn, Perelman Sch Med, Dept Med, Cell Culture & iPS Core,Div Gastroenterol, 956 Biomed Res Bldg,421 Curie Blvd, Philadelphia, PA 19104 USA.	nakagawh@pennmedicine.upenn.edu; anil2@pennmedicine.upenn.edu; natsugoe@m2.kufm.kagoshima-u.ac.jp	Ohashi, Shinya/AAD-8920-2022	Nakagawa, Hiroshi/0000-0001-7330-4863; Kijima, Takashi/0000-0003-1681-7069; Hara, Takeo/0000-0001-6591-0759; Kikuchi, Osamu/0000-0001-5012-5897	Ministry of Education, Culture, Sports, Science and Technology of JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [17H04285, 15K10108]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01CA098101, U54CA163004, R01DK114436, R01AA026297, R01AA022986]; University of Pennsylvania Center of Excellence in Environmental Toxicology [K01DK103953, F32CA174176, T32DK007066, K08DK106444, P30ES013508]; American Cancer SocietyAmerican Cancer Society [RP-10-033-01-CCE]; NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases [P30DK050306]; Japan Society for the Promotion of Science Postdoctoral FellowshipMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science; Fonds de Recherche du Quebec - Sante Postdoctoral Fellowship [P-Giroux-27692, P-Giroux-31601]; Molecular Pathology and Imaging, Molecular Biology/Gene Expression, Cell Culture/iPS and Mouse Core Facilities; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P01CA098101, U54CA163004] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [K08DK106444, R01DK114436, K01DK103953, P30DK050306, T32DK007066] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [P30ES013508] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISMUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [R01AA026297, R01AA022986] Funding Source: NIH RePORTER	This study was supported by the Grant-in-Aid for challenging Exploratory Research, Grant in Aid for Scientific Research B and Grant in Aid for Scientific Research C from the Ministry of Education, Culture, Sports, Science and Technology of Japan (17H04285 to SN; and 15K10108 to YK). This study was also supported by the following NIH Grants: P01CA098101 (HN, KT, KAW, VG, AJK, AB, JAD, AKR), U54CA163004 (HN, GGG, AKR), R01DK114436 (HN), R01AA026297 (HN), R01AA022986 (NGA), P30ES013508 University of Pennsylvania Center of Excellence in Environmental Toxicology (HN and AKR), K01DK103953 (KAW), F32CA174176 (KAW), T32DK007066 (KAW), K08DK106444 (ABM), the American Cancer Society RP-10-033-01-CCE (AKR), NIH/NIDDK P30DK050306 Center of Molecular Studies in Digestive and Liver Diseases, The Molecular Pathology and Imaging, Molecular Biology/Gene Expression, Cell Culture/iPS and Mouse Core Facilities. KT is a recipient of the Japan Society for the Promotion of Science Postdoctoral Fellowship. VG is a recipient of the Fonds de Recherche du Quebec - Sante Postdoctoral Fellowship (P-Giroux-27692 and P-Giroux-31601).	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Mol. Gastroenterol. Hepatol.		2019	7	1					73	91		10.1016/j.jcmgh.2018.09.003			19	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	HF4DF	WOS:000454182700005	30510992	gold, Green Published			2022-04-25	
J	Zhang, W; Yuan, WT; Song, JM; Wang, SJ; Gu, XM				Zhang, Wei; Yuan, Weitang; Song, Junmin; Wang, Shijun; Gu, Xiaoming			LncRNA CPS1-IT1 suppresses EMT and metastasis of colorectal cancer by inhibiting hypoxia-induced autophagy through inactivation of HIF-1 alpha	BIOCHIMIE			English	Article						CPS1 intronic transcript 1 (CPS1-IT1); Colorectal carcinoma (CRC); Hypoxia-inducible factor-1 alpha (HIF-1 alpha); Epithelial-mesenchymal transition (EMT); Autophagy	INDUCIBLE FACTOR-1-ALPHA; POOR-PROGNOSIS; NECK-CANCER; EXPRESSION; RNA; CELLS; HIF-1; GENE; HEAD; COEXPRESSION	Objective: Hypoxia is a common phenomenon in solid tumor microenvironment. Thereby, the aim of this study was to investigate the molecular mechanisms of tumor metastasis and epithelial-mesenchymal transition (EMT) regulated by lncRNA CPS1 intronic transcript 1 (CPS1-IT1) under hypoxia in CRC. Methods: Expression of lncRNA CPS1-IT1, hypoxia-inducible factor-1 alpha (HIF-1 alpha) and autophagy related protein (LC3) were initially assessed in human CRC tissues and in a series of CRC cell lines. The relationship of CPS1-IT1, HIF-1 alpha and autophagy were analyzed in CRC were performed through in vitro and in vivo functional assays. Results: Expression of CPS1-IT1 were significantly reduced, while HIF-1 alpha and LC3-II were increased in CRC tissues and cell lines. Then, in vitro assays revealed that CPS1-IT1 suppresses EMT and autophagy by inhibiting the activation of HIF-1 alpha in CRC. An in vivo animal model also demonstrated the tumor suppressor mechanism of CPS1-IT1. Conclusion: In this study, we found that hypoxia induce autophagy, and inhibition of autophagy could suppress tumor metastasis and EMT in CRC. Additionally, lncRNA CPS1-IT might suppresses metastasis and EMT by inhibiting hypoxia-induced autophagy through inactivation of HIF-1 alpha in CRC. (C) 2017 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.	[Zhang, Wei; Yuan, Weitang; Song, Junmin; Wang, Shijun; Gu, Xiaoming] Zhengzhou Univ, Affiliated Hosp 1, Dept Colorectal & Anal Surg, 1 Jianshe East Rd, Zhengzhou 450052, Henan, Peoples R China		Zhang, W (corresponding author), Zhengzhou Univ, Affiliated Hosp 1, Dept Colorectal & Anal Surg, 1 Jianshe East Rd, Zhengzhou 450052, Henan, Peoples R China.	weiwei509@yeah.net					Adams JM, 2009, ACTA PHYSIOL HUNG, V96, P19, DOI 10.1556/APhysiol.96.2009.1.2; Bohensky J, 2007, AUTOPHAGY, V3, P207, DOI 10.4161/auto.3708; Braicu EI, 2014, ONCOTARGETS THER, V7, P1563, DOI 10.2147/OTT.S65373; Bryant CS, 2010, ARCH GYNECOL OBSTET, V282, P677, DOI 10.1007/s00404-010-1381-9; Chen N, 2011, CANCER BIOL THER, V11, P157, DOI 10.4161/cbt.11.2.14622; Douaiher J, 2017, J SURG ONCOL, V115, P619, DOI 10.1002/jso.24578; Eckert AW, 2011, HISTOPATHOLOGY, V58, P1136, DOI 10.1111/j.1365-2559.2011.03806.x; Eddy SR, 2001, NAT REV GENET, V2, P919, DOI 10.1038/35103511; Fang XY, 2015, CANCER LETT, V356, P357, DOI 10.1016/j.canlet.2014.11.005; He Y, 2014, CANCER LETT, V344, P20, DOI 10.1016/j.canlet.2013.10.021; Indelicato M, 2010, J CELL PHYSIOL, V223, P359, DOI 10.1002/jcp.22041; Janssen HL, 2005, HEAD NECK-J SCI SPEC, V27, P622, DOI 10.1002/hed.20223; Jemal A, 2011, CA-CANCER J CLIN, V61, P69, DOI [10.3322/caac.20107, 10.3322/caac.20115]; Jensen RL, 2006, J NEURO-ONCOL, V78, P233, DOI 10.1007/s11060-005-9103-z; Jiang LC, 2014, J ORAL PATHOL MED, V43, P265, DOI 10.1111/jop.12124; Jiang LC, 2012, PATHOL RES PRACT, V208, P635, DOI 10.1016/j.prp.2012.07.008; Lee J., 2008, CANCER RES, V68, P2049; Ling FC, 2006, ANTICANCER RES, V26, P4505; Lukas J, 2015, EMBO REP, V16, P1413, DOI 10.15252/embr.201541309; Ma SL, 2015, MOL MED REP, V12, P7915, DOI 10.3892/mmr.2015.4435; Malek E, 2014, ONCOTARGET, V5, P8027, DOI 10.18632/oncotarget.2469; Menrad H, 2010, HEPATOLOGY, V51, P2183, DOI 10.1002/hep.23597; Naves T, 2013, BIOCHEM PHARMACOL, V85, P1153, DOI 10.1016/j.bcp.2013.01.022; Norikane T, 2014, NUCL MED COMMUN, V35, P30, DOI 10.1097/MNM.0000000000000010; Ogawa K, 2011, ANTICANCER RES, V31, P2351; Prensner JR, 2011, CANCER DISCOV, V1, P391, DOI 10.1158/2159-8290.CD-11-0209; Rafiemanesh H, 2016, EXCLI J, V15, P738, DOI 10.17179/excli2016-346; Sanchez-Barriga JJ, 2017, REV GASTROENTEROL ME, V82, P217, DOI 10.1016/j.rgmx.2016.10.005; Siegel R, 2012, CA-CANCER J CLIN, V62, P10, DOI 10.3322/caac.20138; Song ZC, 2012, CELL PROLIFERAT, V45, P239, DOI 10.1111/j.1365-2184.2012.00810.x; Subarsky P, 2003, CLIN EXP METASTAS, V20, P237, DOI 10.1023/A:1022939318102; Suresh V., 2015, REVEALING PROTEIN IN; Toustrup K, 2012, SEMIN RADIAT ONCOL, V22, P119, DOI 10.1016/j.semradonc.2011.12.006; Wang F, 2015, ONCOTARGET, V6, P1; WANG GL, 1993, P NATL ACAD SCI USA, V90, P4304, DOI 10.1073/pnas.90.9.4304; Wang TH, 2016, ONCOTARGET, V7, P43588, DOI 10.18632/oncotarget.9635; White E, 2009, CLIN CANCER RES, V15, P5308, DOI 10.1158/1078-0432.CCR-07-5023; Wu HW, 2015, MOL MED REP, V12, P6467, DOI 10.3892/mmr.2015.4255; Zhang KL, 2015, ONCOTARGET, V6, P537, DOI 10.18632/oncotarget.2681	39	55	57	1	11	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER	ISSY-LES-MOULINEAUX	65 RUE CAMILLE DESMOULINS, CS50083, 92442 ISSY-LES-MOULINEAUX, FRANCE	0300-9084	1638-6183		BIOCHIMIE	Biochimie	JAN	2018	144						21	27		10.1016/j.biochi.2017.10.002			7	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	FQ6TH	WOS:000418496400003	29017924				2022-04-25	
J	Papadia, P; Barozzi, F; Hoeschele, JD; Piro, G; Margiotta, N; Di Sansebastiano, GP				Papadia, Paride; Barozzi, Fabrizio; Hoeschele, James D.; Piro, Gabriella; Margiotta, Nicola; Di Sansebastiano, Gian-Pietro			Cisplatin, Oxaliplatin, and Kiteplatin Subcellular Effects Compared in a Plant Model	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						cytoskeleton; vacuoles; transgenic Arabidopsis; cisplatin; kiteplatin; oxaliplatin	ANTITUMOR-ACTIVITY; ARABIDOPSIS-THALIANA; AUTOPHAGY; CANCER; PROTEIN; DRUGS; COMPLEXES; ANTICANCER; RESISTANCE; TRANSPORT	The immediate visual comparison of platinum chemotherapeutics' effects in eukaryotic cells using accessible plant models of transgenic Arabidopsis thaliana is reported. The leading anticancer drug cisplatin, a third generation drug used for colon cancer, oxaliplatin and kiteplatin, promising Pt-based anticancer drugs effective against resistant lines, were administered to transgenic A. thaliana plants monitoring their effects on cells from different tissues. The transgenic plants' cell cytoskeletons were labelled by the green fluorescent protein (GFP)-tagged microtubule-protein TUA6 (TUA6-GFP), while the vacuolar organization was evidenced by two soluble chimerical GFPs (GFPChi and AleuGFP) and one transmembrane GFP-tagged tonoplast intrinsic protein 1-1 (TIP1.1-GFP). The three drugs showed easily recognizable effects on plant subcellular organization, thereby providing evidence for a differentiated drug targeting. Genetically modified A. thaliana are confirmed as a possible rapid and low-cost screening tool for better understanding the mechanism of action of human anticancer drugs.	[Papadia, Paride; Barozzi, Fabrizio; Piro, Gabriella; Di Sansebastiano, Gian-Pietro] Univ Salento, Dept Biotechnol & Environm Sci, Via Monteroni Ctr Ecotekne, I-73100 Lecce, Italy; [Hoeschele, James D.] Eastern Michigan Univ, Dept Chem, Ypsilanti, MI 48197 USA; [Margiotta, Nicola] Univ Bari Aldo Moro, Dept Chem, Via E Orabona 4, I-70125 Bari, Italy		Di Sansebastiano, GP (corresponding author), Univ Salento, Dept Biotechnol & Environm Sci, Via Monteroni Ctr Ecotekne, I-73100 Lecce, Italy.; Margiotta, N (corresponding author), Univ Bari Aldo Moro, Dept Chem, Via E Orabona 4, I-70125 Bari, Italy.	paride.papadia@unisalento.it; fabrizio.barozzi@unisalento.it; hoeschel@chemistry.msu.edu; gabriella.piro@unisalento.it; nicola.margiotta@uniba.it; gp.disansebastiano@unisalento.it	Papadia, Paride/AAC-9472-2021; Barozzi, Fabrizio/AAY-9844-2021; Di Sansebastiano, Gian Pietro/I-7193-2012; Margiotta, Nicola/AAE-3975-2021	Papadia, Paride/0000-0001-9611-3824; Barozzi, Fabrizio/0000-0003-1409-2324; Di Sansebastiano, Gian Pietro/0000-0001-5388-0695; Margiotta, Nicola/0000-0003-4034-875X	Italian Ministero dell'Universita e della; European UnionEuropean Commission [COST CM1105]	Paride Papadia would like to thank the Italian Ministero dell'Universita e della Ricerca for ex-60% funds. Gian-Pietro Di Sansebastiano would like to thank project no14 "Reti di Laboratori Pubblici di ricerca, SELGE", Regione Puglia. Nicola Margiotta would like to thank the University of Bari (Italy), the Italian Ministero dell'Universita e della Ricerca, the Inter-University Consortium for Research on the Chemistry of Metal Ions in Biological Systems (C.I.R.C.M.S.B.), and the European Union (COST CM1105: Functional metal complexes that bind to biomolecules) for support.	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J	Xie, GY; Sun, LX; Li, YL; Chen, BC; Wang, C				Xie, Gangyin; Sun, Linxiao; Li, Yonglin; Chen, Bicheng; Wang, Cheng			Periplocin inhibits the growth of pancreatic cancer by inducing apoptosis via AMPK-mTOR signaling	CANCER MEDICINE			English	Article						apoptosis; pancreatic cancer; Periplocin; proliferation	ACTIVATED PROTEIN-KINASE; COLON-CANCER; CELL-GROWTH; IN-VITRO; AUTOPHAGY; DEATH; VIVO; PATHWAY	Background Periplocin is a monomeric compound that exhibits anti-tumor activities. It is extracted from Cortex Periplocae. Objective This study aimed at determining the effect of periplocin treatment on the apoptosis and proliferation of human pancreatic cancer cells, and to elucidate on its mechanisms of action. Methods PANC1 and cfpac1 cells were treated with periplocin. Cell proliferation was detected by RTCA, Ki67 immunofluorescence, and a clonogenic assay. The transwell assay was used to examine cell migration and invasion functions. The expression of apoptosis-associated proteins was detected by flow cytometry and western blotting. Total RNA was extracted from the treated and untreated group of PANC1 cells for RNA-seq detection and analysis. Differentially expressed genes were screened for GO biological process and KEGG pathway analysis. Finally, CFPAC1 cells were subcutaneously inoculated into BALB / c nude mice to assess tumor growth. Results Periplocin inhibited the proliferation of PANC1 and CFPAC1 cells and induced their apoptosis by activating the AMPK/mTOR pathway and inhibiting p70 S6K. It also attenuated the cell migration, invasion, and inhibited the growth of cfpac1 xenografts in nude mice. Conclusions Periplocin inhibits human pancreatic cancer cell proliferation and induces their apoptosis by activating the AMPK / mTOR pathway.	[Xie, Gangyin; Sun, Linxiao; Li, Yonglin; Chen, Bicheng; Wang, Cheng] Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Diag & Treatment Severe Hepatopancreat Di, Zhejiang Prov Top Key Discipline Surg, Wenzhou, Zhejiang, Peoples R China		Chen, BC; Wang, C (corresponding author), Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Diag & Treatment Severe Hepatopancreat Di, Zhejiang Prov Top Key Discipline Surg, Wenzhou, Zhejiang, Peoples R China.	bichengchen@hotmail.com; wangchengmandy@126.com			Wenzhou Municipal Science and Technology Bureau [Y20190073]; Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LQ20H030004]	This study was supported by grants from the Wenzhou Municipal Science and Technology Bureau (Y20190073) and Natural Science Foundation of Zhejiang Province (LQ20H030004)	Barroso-Chinea P, 2020, AUTOPHAGY, V16, P1279, DOI 10.1080/15548627.2019.1668606; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Chen MB, 2015, CARCINOGENESIS, V36, P1061, DOI 10.1093/carcin/bgv094; Chen MB, 2013, CELL SIGNAL, V25, P1993, DOI 10.1016/j.cellsig.2013.05.026; Cheng C.F, 2013, EVID-BASED COMPL ALT, V2013, DOI DOI 10.1155/2013/958025; Choi YH, 2018, GEN PHYSIOL BIOPHYS, V37, P129, DOI 10.4149/gpb_2017026; Guo H, 2013, J ETHNOPHARMACOL, V147, P447, DOI 10.1016/j.jep.2013.03.036; He XY, 2014, WORLD J GASTROENTERO, V20, P11241, DOI 10.3748/wjg.v20.i32.11241; Howes N, 2004, CLIN GASTROENTEROL H, V2, P252, DOI 10.1016/S1542-3565(04)00013-8; Hu Q, 2018, FRONT PHARMACOL, V9, DOI 10.3389/fphar.2018.01150; Inoki K, 2003, CELL, V115, P577, DOI 10.1016/S0092-8674(03)00929-2; Kang JI, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0144368; Ke R, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-23780-x; Kim J, 2011, NAT CELL BIOL, V13, P132, DOI 10.1038/ncb2152; Kurgan N, 2017, CANCERS, V9, DOI 10.3390/cancers9050046; Lai SL, 2018, PHYTOMEDICINE, V42, P144, DOI 10.1016/j.phymed.2018.03.027; Law BYK, 2016, ONCOTARGET, V7, P8090, DOI 10.18632/oncotarget.6980; Lee JS, 2019, INT J MOL MED, V43, P1969, DOI 10.3892/ijmm.2019.4122; Li L, 2016, CELL PHYSIOL BIOCHEM, V38, P1939, DOI 10.1159/000445555; Liu J, 2019, CANCER CELL INT, V19, DOI 10.1186/s12935-019-1054-0; Liu XJ, 2019, INT J CANCER, V145, P1007, DOI 10.1002/ijc.32285; Lohberger B, 2020, PHYTOMEDICINE, V76, DOI 10.1016/j.phymed.2020.153262; Lohberger B, 2018, PHYTOMEDICINE, V51, P162, DOI 10.1016/j.phymed.2018.10.008; Lu ZJ, 2010, CELL PHYSIOL BIOCHEM, V26, P609, DOI 10.1159/000322328; Mihaylova MM, 2011, NAT CELL BIOL, V13, P1016, DOI 10.1038/ncb2329; Pavan ICB, 2016, PROTEOMICS, V16, P2650, DOI 10.1002/pmic.201500249; Song LH, 2017, MOLECULES, V22, DOI 10.3390/molecules22111934; Su QL, 2016, AM J CANCER RES, V6, P498; Tetsuo F, 2019, CANCER SCI, V110, P3761, DOI 10.1111/cas.14204; Tian YX, 2020, J CELL PHYSIOL, V235, P442, DOI 10.1002/jcp.28984; Tsoi H, 2017, ONCOGENE, V36, P6109, DOI 10.1038/onc.2017.86; Wang FF, 2020, J CELL PHYSIOL, V235, P4302, DOI 10.1002/jcp.29307; Xue R, 2018, BIOMED RES INT, V2018, DOI 10.1155/2018/4283673; Yun SM, 2014, PHYTOTHER RES, V28, P458, DOI 10.1002/ptr.5015; Zeng P, 2016, ONCOTARGET, V7, P76327, DOI 10.18632/oncotarget.10153; Zhang Z K, 2020, Zhonghua Wai Ke Za Zhi, V58, P22, DOI 10.3760/cma.j.issn.0529-5815.2020.01.006; Zhao LM, 2010, ONCOL REP, V24, P375, DOI 10.3892/or_00000870	37	6	6	2	6	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	2045-7634			CANCER MED-US	Cancer Med.	JAN	2021	10	1					325	336		10.1002/cam4.3611		NOV 2020	12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	QB0TG	WOS:000591693500001	33231372	Green Published, gold			2022-04-25	
J	Schneider, NFZ; Cerella, C; Lee, JY; Mazumder, A; Kim, KR; de Carvalho, A; Munkert, J; Padua, RM; Kreis, W; Kim, KW; Christov, C; Dicato, M; Kim, HJ; Han, BW; Braga, FC; Simoes, CMO; Diederich, M				Schneider, Naira F. Z.; Cerella, Claudia; Lee, Jin-Young; Mazumder, Aloran; Kim, Kyung Rok; de Carvalho, Annelise; Munkert, Jennifer; Padua, Rodrigo M.; Kreis, Wolfgang; Kim, Kyu-Won; Christov, Christo; Dicato, Mario; Kim, Hyun-Jung; Han, Byung Woo; Braga, Fernao C.; Simoes, Claudia M. O.; Diederich, Marc			Cardiac Glycoside Glucoevatromonoside Induces Cancer Type-Specific Cell Death	FRONTIERS IN PHARMACOLOGY			English	Article						cardiac glycoside; glucoevatromonoside; apoptosis; non-canonical cell death; lung cancer	LUNG-CANCER; CYCLIN B1; CARDIOTONIC STEROIDS; SOLID TUMORS; DNA-DAMAGE; BRAZILIAN CULTIVAR; SIGNALING PATHWAYS; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER; DIGITALIS-LANATA	Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC) and high-affinity binding to the Na+/K+-ATPase a subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission electron microscopy, live cell imaging and flow cytometry. This non-canonical cell death was not preceded or accompanied by exacerbation of autophagy. In the presence of GEV, markers of autophagic flux (e.g. LC3I-II conversion) were impacted, even in presence of bafilomycin A1. Cell death induction remained unaffected by calpain, cathepsin, parthanatos, or necroptosis inhibitors. Interestingly, GEV triggered caspase-dependent apoptosis in U937 acute myeloid leukemia cells, witnessing cancer-type specific cell death induction. Differential cell cycle modulation by this CG led to a G2/M arrest, cyclin B1 and p53 downregulation in A549, but not in U937 cells. We further extended the anti-cancer potential of GEV to 3D cell culture using clonogenic and spheroid formation assays and validated our findings in vivo by zebrafish xenografts. Altogether, GEV shows an interesting anticancer profile with the ability to exert cytotoxic effects via induction of different cell death modalities.	[Schneider, Naira F. Z.; de Carvalho, Annelise; Simoes, Claudia M. O.] Univ Fed Santa Catarina, Ctr Ciencias Saude, Dept Ciencias Farmaceut, Lab Virol Applicada, Florianopolis, SC, Brazil; [Cerella, Claudia; Dicato, Mario] Hop Kirchberg, Lab Biol Mol & Cellulaire Canc, Luxembourg, Luxembourg; [Cerella, Claudia; Lee, Jin-Young; Mazumder, Aloran; Kim, Kyung Rok; Han, Byung Woo; Diederich, Marc] Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Dept Pharm, Seoul, South Korea; [Munkert, Jennifer; Kreis, Wolfgang] Friedrich Alexander Univ, Dept Biol, Erlangen, Germany; [Padua, Rodrigo M.; Braga, Fernao C.] Univ Fed Minas Gerais, Fac Farm, Dept Prod Farmaceut, Belo Horizonte, MG, Brazil; [Kim, Kyu-Won] Seoul Natl Univ, Coll Pharm, SNU Harvard Neurovasc Protect Ctr, Seoul, South Korea; [Kim, Kyu-Won] Seoul Natl Univ, Res Inst Pharmaceut Sci, Seoul, South Korea; [Christov, Christo] Univ Lorraine, Fac Med, Nancy, France; [Kim, Hyun-Jung] Chung Ang Univ, Coll Pharm, Seoul, South Korea		Diederich, M (corresponding author), Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Dept Pharm, Seoul, South Korea.	marcdiederich@snu.ac.kr	Braga, Fernão/AAO-3888-2020; Kim, Kyu Won/AAJ-7213-2020; Schneider, Naira FZ/L-9215-2013; Braga, Fernão C/E-3236-2016; Diederich, Marc/O-7335-2015; de Padua, Rodrigo Maia/H-5341-2018	Braga, Fernão/0000-0001-9468-376X; Braga, Fernão C/0000-0001-9468-376X; Diederich, Marc/0000-0003-0115-4725; de Padua, Rodrigo Maia/0000-0002-9939-6900	Waxweiler grant for cancer prevention research from the Action Lions Vaincre le Cancer; BK21 and Televie; CAPES PDSE programCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [99999.014368/2013-07]; CAPES/MEC (Ministry of Education); CNPq/MCTI (Ministry of Science, Technology and Innovation); CNPqConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [472544/2013-6, 490057/2011-0]; CAPESCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [PNPD 2257/2011]; Marie Curie Foundation/IRSES/European Community [295251]; BK21Ministry of Education & Human Resources Development (MOEHRD), Republic of Korea; Recherches Scientifiques Luxembourg (RSL); National Research Foundation (NRF); MEST of Korea for Tumor Microenvironment Global Core Research Center (GCRC) [NRF-2011-0030001]; Seoul National University Research Grant; Brain Korea (BK21) PLUS program; Recherche Cancer et Sang foundation; Recherches Scientifiques Luxembourg association; Een Haerz fir kriibskrank Kanner association; Action LIONS Vaincre le Cancer association; Televie Luxembourg	ClC was supported by a Waxweiler grant for cancer prevention research from the Action Lions Vaincre le Cancer, by BK21 and Televie. NS was supported by CAPES PDSE program 99999.014368/2013-07. The Brazilian authors would like to thank the funding agencies CAPES/MEC (Ministry of Education) and CNPq/MCTI (Ministry of Science, Technology and Innovation) for their research scholarships. This work was also supported by CNPq (Grants 472544/2013-6 and 490057/2011-0), CAPES (Grant PNPD 2257/2011), and Marie Curie Foundation/IRSES/European Community (Grant 295251). J-YL and AM were supported by BK21 and Recherches Scientifiques Luxembourg (RSL). Research at SNU is supported by the National Research Foundation (NRF) by the MEST of Korea for Tumor Microenvironment Global Core Research Center (GCRC) grant [grant number NRF-2011-0030001; by the Seoul National University Research Grant and by Brain Korea (BK21) PLUS program]. LBMCC was supported by the Recherche Cancer et Sang foundation, the Recherches Scientifiques Luxembourg association, by the Een Haerz fir kriibskrank Kanner association, by the Action LIONS Vaincre le Cancer association and by Televie Luxembourg.	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Pharmacol.	MAR 1	2018	9								70	10.3389/fphar.2018.00070			17	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	FX8VS	WOS:000426374400001	29545747	Green Published, gold			2022-04-25	
J	He, Y; Zhang, L; Tan, F; Wang, LF; Liu, DH; Wang, RJ; Yin, XZ				He, Yong; Zhang, Ling; Tan, Fei; Wang, Li-Fang; Liu, De-Hui; Wang, Rong-Juan; Yin, Xiong-Zhang			MiR-153-5p promotes sensibility of colorectal cancer cells to oxaliplatin via targeting Bcl-2-mediated autophagy pathway	BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY			English	Article						Colorectal cancer; L-OHP resistant; miR-153-5p; Bcl-2; autophagy		Oxaliplatin (L-OHP) is one of the effective chemotherapeutic drugs for colorectal cancer (CRC). Further investigation into the molecular mechanism of chemoresistance could improve outcomes for patients with colorectal cancer. Recently, microRNAs have been reported as a key in drug resistance of tumors. In this study, we aimed to investigate the effects of miR-153-5p in L-OHP-resistant CRC cells, and its underlying mechanism. Downregulation of miR-153-5p was observed in CRC cells, while upregulation of miR-153-5p enhances the chemosensitivity of CRC/L-OHP cells. The autophagy of CRC/L-OHP cells was markedly increased after exposure to L-OHP but abolished by the upregulation of miR-153-5p. Dual-luciferase reporter assays validated that Bcl-2 was a direct target of miR-153-5p. In conclusion, our data suggested that miR-153-5p was a mediator of cisplatin resistance in colorectal cancer by affecting Bcl-2-mediated autophagy, indicating a new therapeutic target for CRC treatment.	[He, Yong; Tan, Fei; Wang, Li-Fang; Liu, De-Hui; Wang, Rong-Juan] Ganzhou Peoples Hosp, Intravenous Drugs Dispensing Ctr, Ganzhou, Jiangxi, Peoples R China; [Zhang, Ling] FirstPeoples Hosp Xiantao, Dept Pharm, Xiantao, Hubei, Peoples R China; [Yin, Xiong-Zhang] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Pharm, Wuhan, Hubei, Peoples R China		Yin, XZ (corresponding author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Pharm, Wuhan, Hubei, Peoples R China.	xiongzhang027@163.com					Aoyama T, 2017, CANCER MED-US, V6, P2523, DOI 10.1002/cam4.1208; Cowland JB, 2007, APMIS, V115, P1090, DOI 10.1111/j.1600-0463.2007.apm_775.xml.x; Ferlay J, 2010, INT J CANCER, V127, P2893, DOI 10.1002/ijc.25516; Grady WM, 2014, TOXICOL PATHOL, V42, P124, DOI 10.1177/0192623313505155; Kraus S, 2014, CANCER LETT, V347, P15, DOI 10.1016/j.canlet.2014.01.025; Kumar A, 2015, FUTURE MED CHEM, V7, P1535, DOI 10.4155/fmc.15.88; Lai K, 2014, J CLIN PATHOL, V67, P854, DOI 10.1136/jclinpath-2014-202529; Lamb CA, 2013, NAT REV MOL CELL BIO, V14, P759, DOI 10.1038/nrm3696; Liu FF, 2013, ONCOL LETT, V5, P1261, DOI 10.3892/ol.2013.1154; Luan WK, 2018, BIOCHEM BIOPH RES CO, V502, P22, DOI 10.1016/j.bbrc.2018.05.114; Lum JJ, 2005, CELL, V120, P237, DOI 10.1016/j.cell.2004.11.046; Ma J, 2010, CANCER GENE THER, V17, P523, DOI 10.1038/cgt.2010.18; Qian X, 2013, CELL CYCLE, V12, P1385, DOI 10.4161/cc.24477; Santana-Codina N, 2017, ANNU REV CANC BIOL, V1, P19, DOI 10.1146/annurev-cancerbio-041816-122338; Sun DY, 2018, BIOL RES, V51, DOI 10.1186/s40659-018-0203-6; Tanida Isei, 2008, V445, P77, DOI 10.1007/978-1-59745-157-4_4; Ye JJ, 2014, WORLD J GASTROENTERO, V20, P4288, DOI 10.3748/wjg.v20.i15.4288; Zhang CY, 2012, ONCOL LETT, V3, P831, DOI 10.3892/ol.2012.567; Zhang L, 2013, CANCER RES, V73, P6435, DOI 10.1158/0008-5472.CAN-12-3308; Zhang YL, 2019, EBIOMEDICINE, V48, P277, DOI 10.1016/j.ebiom.2019.09.051; Zhou J, 2015, ONCOL REP, V34, P111, DOI 10.3892/or.2015.3952; Zou YH, 2016, MOL MED REP, V14, P1033, DOI 10.3892/mmr.2016.5309	22	6	6	0	2	TAYLOR & FRANCIS LTD	ABINGDON	2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND	0916-8451	1347-6947		BIOSCI BIOTECH BIOCH	Biosci. Biotechnol. Biochem.	AUG 2	2020	84	8					1645	1651		10.1080/09168451.2020.1760784		MAY 2020	7	Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology	MM4LQ	WOS:000538613600001	32380907	Bronze			2022-04-25	
J	Lee, HJ; Kim, JH; Hong, S; Hwang, I; Park, SJ; Kim, TI; Kim, WH; Yu, JW; Kim, SW; Cheon, JH				Lee, Hyun Jung; Kim, Jae Hyeon; Hong, Sujeong; Hwang, Inhwa; Park, Soo Jung; Kim, Tae Il; Kim, Won Ho; Yu, Je-Wook; Kim, Seung Won; Cheon, Jae Hee			Proteomics-based functional studies reveal that galectin-3 plays a protective role in the pathogenesis of intestinal Behcet's disease	SCIENTIFIC REPORTS			English	Article							INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; ER STRESS; AUTOPHAGY; COLITIS; SUSCEPTIBILITY; POLYMORPHISMS; INFLAMMASOMES; ASSOCIATIONS; IL-1-BETA	The pathogenesis of intestinal Behcet's disease (BD) remains poorly understood. Therefore, we aimed to discover and validate biomarkers using proteomics analysis and subsequent functional studies. After two-dimensional electrophoresis, candidate proteins were identified using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS). We validated these results by evaluating the protein levels and their functions in vitro using HT-29 colorectal cancer cells, colon tissues from patients and mice, and murine bone marrow derived macrophages (BMDMs). Of the 30 proteins differentially expressed in intestinal BD tissues, we identified seven using MALDI-TOF/TOF MS. Focusing on galectin-3, we found that TGF-B and IL-10 expression was significantly lower in shLGALS3-transfected cells. Expression of GRP78 and XBP1s and apoptosis rates were all higher in shLGALS3-transfected cells upon the induction of endoplasmic reticulum stress. In response to lipopolysaccharide stimulation, microtubule-associated protein 1 light chain 3B accumulated and lysosomes decreased in these cells. Finally, Salmonella typhimurium infection induced caspase-1 activation and increased IL-1 beta production, which facilitated activation of the NLRC4 inflammasome, in Lgals3(-/-) murine BMDMs compared to wild type BMDMs. Our data suggest that galectin-3 may play a protective role in the pathogenesis of intestinal BD via modulation of ER stress, autophagy, and inflammasome activation.	[Lee, Hyun Jung; Kim, Jae Hyeon; Park, Soo Jung; Kim, Tae Il; Kim, Won Ho; Kim, Seung Won; Cheon, Jae Hee] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea; [Lee, Hyun Jung; Kim, Jae Hyeon; Park, Soo Jung; Kim, Tae Il; Kim, Won Ho; Kim, Seung Won; Cheon, Jae Hee] Yonsei Univ, Coll Med, Inst Gastroenterol, Seoul, South Korea; [Lee, Hyun Jung] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea; [Lee, Hyun Jung] Seoul Natl Univ, Coll Med, Liver Res Inst, Seoul, South Korea; [Kim, Jae Hyeon; Kim, Seung Won; Cheon, Jae Hee] Yonsei Univ, Coll Med, Brain Korea 21 PLUS Project Med Sci, Seoul, South Korea; [Hong, Sujeong; Hwang, Inhwa; Yu, Je-Wook] Yonsei Univ, Brain Korea 21 PLUS Project Med Sci, Dept Microbiol, Inst Immunol & Immunol Dis,Coll Med, Seoul, South Korea; [Kim, Seung Won; Cheon, Jae Hee] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul, South Korea		Kim, SW; Cheon, JH (corresponding author), Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea.; Kim, SW; Cheon, JH (corresponding author), Yonsei Univ, Coll Med, Inst Gastroenterol, Seoul, South Korea.; Kim, SW; Cheon, JH (corresponding author), Yonsei Univ, Coll Med, Brain Korea 21 PLUS Project Med Sci, Seoul, South Korea.; Kim, SW; Cheon, JH (corresponding author), Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul, South Korea.	swk21c@hanmail.net; GENIUSHEE@yuhs.ac	Cheon, Jae Hee/B-4523-2015	Cheon, Jae Hee/0000-0002-2282-8904; Kim, Seung Won/0000-0002-1692-1192; Hwang, Inhwa/0000-0001-5235-3519; Yu, Je-Wook/0000-0001-5943-4071; Kim, Jaehyeon/0000-0003-0064-6656; Kim, Tae Il/0000-0003-4807-890X; Kim, Won Ho/0000-0002-5682-9972	National Research Foundation of Korea (NRF) - Korea government (MSIP) [NRF-2014R1A1A1008096, NRF-2017R1A1A1A05001011]; faculty research grant of Yonsei University College of Medicine [6-2012-0135]; Korea Health Technology R&D Project through Korea Health Industry Development Institute (KHIDI); Ministry of Health & Welfare, Republic of KoreaMinistry of Health & Welfare, Republic of Korea [HI13C1345]	This research was supported by National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIP) (NRF-2014R1A1A1008096, NRF-2017R1A1A1A05001011), a faculty research grant of Yonsei University College of Medicine (6-2012-0135), a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI13C1345). We also wish to acknowledge technical support from Yonsei Proteome Research Center (www.proteomix.org).	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J	Kang, MR; Kim, MS; Oh, JE; Kim, YR; Song, SY; Kim, SS; Ahn, CH; Yoo, NJ; Lee, SH				Kang, Mi Ran; Kim, Min Sung; Oh, Ji Eun; Kim, Yoo Ri; Song, Sang Yong; Kim, Sung Soo; Ahn, Chang Hyeok; Yoo, Nam Jin; Lee, Sug Hyung			Frameshift mutations of autophagy-related genes ATG2B, ATG5, ATG9B and ATG12 in gastric and colorectal cancers with microsatellite instability	JOURNAL OF PATHOLOGY			English	Article						autophagy; ATG; MSI; mutation; gastric cancer; colorectal cancer	INACTIVATING MUTATIONS; PROTEIN; CARCINOMAS; BECLIN-1; DEATH; UVRAG; EXPRESSION; APOPTOSIS; PATHWAYS; THERAPY	Mounting evidence indicates that alterations of autophagy processes are directly involved in the development of many human diseases, including cancers. Autophagy-related gene (ATG) products are main players in the autophagy process. In humans there are 16 known ATG genes, of which four (ATG2B, ATG5, ATG9B and ATG12) have mononucleotide repeats with seven or more nucleotides. Frameshift mutations of genes with mononucleotide repeats are features of cancers with microsatellite instability (MSI). It is not known whether ATG genes with mononucleotide repeats are altered by frameshift mutations in gastric and colorectal carcinomas with MSI. For this, we analysed the mononecleotide repeats in ATG2B, ATG5, ATG9B and ATG12 in 32 gastric carcinomas with high MSI (MSI-H), 13 gastric carcinomas with low MSI (MSI-L), 43 colorectal carcinomas with MSI-H and 15 colorectal carcinomas with MSI-L by a single-strand conformation polymorphism (SSCP) analysis. We found ATG2B, ATG5, ATG9B and ATG12 mutations in 10, 2, 13 and 0 cancers, respectively. The mutations were detected in MSI-H cancers but not in MSI-L cancers. Gastric and colorectal cancers with MSI-H harboured one or more ATG mutations in 28.1% and 27.9%, respectively. Our data indicate that frameshift mutations in ATG genes with mononucleotide repeats are common in gastric and colorectal carcinomas with MSI-H, and suggest that these mutations may contribute to cancer development by deregulating the autophagy process. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.	[Kang, Mi Ran; Kim, Min Sung; Oh, Ji Eun; Kim, Yoo Ri; Yoo, Nam Jin; Lee, Sug Hyung] Catholic Univ Korea, Coll Med, Dept Pathol, Seoul 137701, South Korea; [Song, Sang Yong] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea; [Ahn, Chang Hyeok] Catholic Univ Korea, Coll Med, Dept Internal Med, Seoul 137701, South Korea; [Ahn, Chang Hyeok] Catholic Univ Korea, Coll Med, Dept Gen Surg, Seoul 137701, South Korea		Lee, SH (corresponding author), Catholic Univ Korea, Coll Med, Dept Pathol, 505 Bonpo Dong, Seoul 137701, South Korea.	suhulee@catholic.ac.kr			Ministry for Health, Welfare and Family Affairs, KoreaMinistry of Health & Welfare, Republic of Korea [A080083]	This study was supported by the Ministry for Health, Welfare and Family Affairs, Korea (Grant No. A080083).	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Pathol.	APR	2009	217	5					702	706		10.1002/path.2509			5	Oncology; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pathology	425YU	WOS:000264674900010	19197948				2022-04-25	
J	Zhang, RN; Pan, T; Xiang, Y; Zhang, MM; Feng, J; Liu, SP; Duan, T; Chen, P; Zhai, BT; Chen, XY; Wang, WG; Chen, B; Han, XM; Chen, LX; Yan, LL; Jin, T; Liu, Y; Li, GH; Huang, XX; Zhang, WZ; Sun, YT; Li, QJ; Zhang, Q; Zhuo, J; Xie, T; Wu, QB; Sui, XB				Zhang, Ruonan; Pan, Ting; Xiang, Yu; Zhang, Mingming; Feng, Jiao; Liu, Shuiping; Duan, Ting; Chen, Peng; Zhai, Bingtao; Chen, Xiaying; Wang, Wengang; Chen, Bi; Han, Xuemeng; Chen, Liuxi; Yan, Lili; Jin, Ting; Liu, Ying; Li, Guohua; Huang, Xingxing; Zhang, Wenzheng; Sun, Yitian; Li, Qiujie; Zhang, Qin; Zhuo, Lvjia; Xie, Tian; Wu, Qibiao; Sui, Xinbing			beta-Elemene Reverses the Resistance of p53-Deficient Colorectal Cancer Cells to 5-Fluorouracil by Inducing Pro-death Autophagy and Cyclin D3-Dependent Cycle Arrest	FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY			English	Article						colorectal cancer; p53; beta-elemene; 5-fluorouracil; autophagy; cell cycle; drug resistance	DOWN-REGULATION; KINASE; INHIBITION; STATISTICS; EXPRESSION; TOXICITY; EFFICACY; GROWTH	Objective Colorectal cancer is a malignant tumor of the digestive system with high morbidity and mortality. 5-fluorouracil remains a widely used chemotherapeutic drug in the treatment of advanced colorectal cancer, but chemotherapy drugs are prone to develop drug resistance, p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to 5-fluorouracil. beta-elemene has been proved to have the potential of reverse chemotherapy drug resistance, but the mechanism is unknown. This study aimed to investigate the effect of beta-elemene to 5-fluorouracil in drug-resistant p53-deficient colorectal cancer cells HCT116p53(-/-), and determine the possible molecular mechanism of beta-elemene to reverse 5-fluorouracil resistance. Methods The effect of beta-elemene on HCT116p53(-/-) cell activity was detected by Cell counting Kit-8. Cell proliferation was detected by monoclonal plate. The apoptosis was detected by flow cytometry and western blot. The autophagy was detected by western blot, immunofluorescence and transmission electron microscope. Determine the role of Cyclin-related protein Cyclin D3 in beta-elemene reversing the resistance of HCT116p53(-/-) to 5-fluorouracil was detected by overexpression of Cyclin D3. The effect of beta-elemene on the tumorigenic ability of p53-deficient colorectal cancer cells was detected establishing HCT116p53(-/-) all line xenograft model. Results For p53 wildtype colorectal cancer cells, beta-elemene could augment the sensitivity of 5-fluorouracil, for p53-deficient colorectal cancer cells, beta-elemene significantly inhibited cell proliferation in a concentration-dependent manner, and reversed the resistance of HCT116p53(-/-) to 5-fluorouracil by inducing pro-death autophagy and Cyclin D3-dependent cycle arrest. Conclusion beta-elemene enhances the sensitivity of p53 wild-type cells to 5-fluorouracil, beta-elemene can reverse the resistance of HCT116p53(-/-) to 5-fluorouracil by inducing pro-death autophagy and Cyclin D3-dependent cycle arrest in p53-deficient colorectal cancer, which will provide a new method for the treatment of p53 deletion colorectal cancer patients.	[Zhang, Ruonan; Pan, Ting; Xiang, Yu; Zhang, Mingming; Feng, Jiao; Liu, Shuiping; Duan, Ting; Chen, Peng; Zhai, Bingtao; Chen, Xiaying; Wang, Wengang; Chen, Bi; Han, Xuemeng; Chen, Liuxi; Yan, Lili; Jin, Ting; Li, Guohua; Huang, Xingxing; Zhang, Wenzheng; Sun, Yitian; Li, Qiujie; Zhang, Qin; Zhuo, Lvjia; Xie, Tian; Sui, Xinbing] Hangzhou Normal Univ, Coll Med, Dept Med Oncol, Holist Integrat Pharm Inst,Affiliated Hosp, Hangzhou, Peoples R China; [Zhang, Ruonan; Pan, Ting; Xiang, Yu; Zhang, Mingming; Feng, Jiao; Liu, Shuiping; Duan, Ting; Chen, Peng; Zhai, Bingtao; Chen, Xiaying; Wang, Wengang; Chen, Bi; Han, Xuemeng; Chen, Liuxi; Yan, Lili; Jin, Ting; Li, Guohua; Huang, Xingxing; Zhang, Wenzheng; Sun, Yitian; Li, Qiujie; Zhang, Qin; Zhuo, Lvjia; Xie, Tian; Sui, Xinbing] Hangzhou Normal Univ, Key Lab Elemene Class Anticanc Chinese Med, Zhejiang Prov & Engn Lab Dev & Applicat Tradit Ch, Hangzhou, Peoples R China; [Zhang, Ruonan; Chen, Bi; Wu, Qibiao; Sui, Xinbing] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Fac Chinese Med, Macau, Peoples R China; [Liu, Ying] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Med Oncol, Hangzhou, Peoples R China		Xie, T; Sui, XB (corresponding author), Hangzhou Normal Univ, Coll Med, Dept Med Oncol, Holist Integrat Pharm Inst,Affiliated Hosp, Hangzhou, Peoples R China.; Xie, T; Sui, XB (corresponding author), Hangzhou Normal Univ, Key Lab Elemene Class Anticanc Chinese Med, Zhejiang Prov & Engn Lab Dev & Applicat Tradit Ch, Hangzhou, Peoples R China.; Wu, QB; Sui, XB (corresponding author), Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Fac Chinese Med, Macau, Peoples R China.	drxiet@aliyun.com; qbwu@must.edu.mo; hzzju@zju.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672932, 81730108, 81874380, 81973635]; Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars [LR18H160001]; Science and Technology Development Fund, Macau SAR [130/2017/A3, 0099/2018/A3]; Zhejiang Province Science and Technology Project of TCM [2019ZZ016]	This work was was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81672932, 81730108, 81874380, and 81973635), Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars (Grant No. LR18H160001), the Science and Technology Development Fund, Macau SAR (File Nos. 130/2017/A3 and 0099/2018/A3), and Zhejiang Province Science and Technology Project of TCM (Grant No. 2019ZZ016).	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Bioeng. Biotechnol.	MAY 8	2020	8								378	10.3389/fbioe.2020.00378			13	Biotechnology & Applied Microbiology; Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Science & Technology - Other Topics	LS9OX	WOS:000536709400001	32457882	Green Published, gold			2022-04-25	
J	Lu, YT; Xiao, LM; Liu, YW; Wang, H; Li, H; Zhou, Q; Pan, J; Lei, BX; Huang, A; Qi, ST				Lu, Yuntao; Xiao, Limin; Liu, Yawei; Wang, Hai; Li, Hong; Zhou, Qiang; Pan, Jun; Lei, Bingxi; Huang, Annie; Qi, Songtao			MIR517C inhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation	AUTOPHAGY			English	Article						autophagy; epithelial-to-mesenchymal (-like) transition; glioblastoma; microRNA; TP53	MALIGNANT GLIOMA-CELLS; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; ADJUVANT TEMOZOLOMIDE; TUMOR PROGRESSION; METABOLIC STRESS; C19MC CLUSTER; IN-VITRO; INDUCTION; P53	The epithelial-to-mesenchymal (-like) transition (EMT), a crucial embryonic development program, has been linked to the regulation of glioblastoma (GBM) progression and invasion. Here, we investigated the role of MIR517C/miR-517c, which belongs to the C19MC microRNA cluster identified in our preliminary studies, in the pathogenesis of GBM. We found that MIR517C was associated with improved prognosis in patients with GBM. Furthermore, following treatment with the autophagy inducer temozolomide (TMZ) and low glucose (LG), MIR517C degraded KPNA2 (karyopherin alpha 2 [RAG cohort 1, importin alpha 1]) and subsequently disturbed the nuclear translocation of TP53 in the GBM cell line U87 in vitro. Interestingly, this microRNA could inhibit autophagy and reduce cell migration and infiltration in U87 cells harboring wild-type (WT) TP53, but not in U251 cells harboring mutant (MU) TP53. Moreover, the expression of epithelial markers (i.e., CDH13/T-cadherin and CLDN1 [claudin 1]) increased, while the expression of mesenchymal markers (i.e., CDH2/N-cadherin, SNAI1/Snail, and VIM [vimentin]) decreased, indicating that the EMT status was blocked by MIR517C in U87 cells. Compared with MIR517C overexpression, MIR517C knockdown promoted infiltration of U87 cells to the surrounding structures in nude mice in vivo. The above phenotypic changes were also observed in TP53(+/+) and TP53(-/-) HCT116 colon cancer cells. In summary, our study provided support for a link between autophagy and EMT status in WT TP53 GBM cells and provided evidence for the signaling pathway (MIR517C-KPNA2-cytoplasmic TP53) involved in attenuating autophagy and eliminating the increased migration and invasion during the EMT.	[Lu, Yuntao; Xiao, Limin; Wang, Hai; Li, Hong; Zhou, Qiang; Pan, Jun; Lei, Bingxi; Qi, Songtao] Southern Med Univ, Nanfang Hosp, Dept Neurosurg, Guangzhou, Guangdong, Peoples R China; [Lu, Yuntao; Liu, Yawei; Qi, Songtao] Nanfang Hosp, Nanfang Neurol Res Inst, Guangzhou, Guangdong, Peoples R China; [Lu, Yuntao; Qi, Songtao] Nanfang Glioma Ctr, Guangzhou, Guangdong, Peoples R China; [Huang, Annie] Hosp Sick Children, Brain Tumor Res Ctr, Toronto, ON M5G 1X8, Canada		Lu, YT (corresponding author), Southern Med Univ, Nanfang Hosp, Dept Neurosurg, Guangzhou, Guangdong, Peoples R China.	lllu2000yun@gmail.com; sjwk_songtao@live.cn		Lu, Yuntao/0000-0003-4125-304X	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81101921]; Natural science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [2014A030313298]; National Key Clinical Specialist Construction Program of China	This project was supported by the National Natural Science Foundation of China (Grant Nos. 81101921), Natural science Foundation of Guangdong Province (Grant Nos. 2014A030313298) and the National Key Clinical Specialist Construction Program of China.	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J	Zhao, HB; Yan, L; Xu, XG; Jiang, CM; Shi, JL; Zhang, YW; Liu, L; Lei, SZ; Shao, DY; Huang, QS				Zhao, Haobin; Yan, Lu; Xu, Xiaoguang; Jiang, Chunmei; Shi, Junling; Zhang, Yawen; Liu, Li; Lei, Shuzhen; Shao, Dongyan; Huang, Qingsheng			Potential of Bacillus subtilis lipopeptides in anti-cancer I: induction of apoptosis and paraptosis and inhibition of autophagy in K562 cells	AMB EXPRESS			English	Article						Lipopeptide; Apoptosis; Anticancer; Paraptosis	CHRONIC MYELOGENOUS LEUKEMIA; BREAST-CANCER; SIGNALING PATHWAY; SURFACTIN; DEATH; ACTIVATION; GROWTH; SUPPRESSION; FIBROBLASTS; TRANSITION	The lipopeptide iturin from Bacillus subtilis has been found to have a potential inhibitory effect on breast cancer, alveolar adenocarcinoma, renal carcinoma, and colon adenocarcinoma. In this study, the potential of B. subtilis lipopeptides (a mixture of iturin homologues, concentration of 42.75%) to inhibit chronic myelogenous leukemia was evaluated using K562 myelogenous leukemia cells. The results showed that the lipopeptides could completely inhibit the growth of K562 at 100 mu M, with an IC50 value of 65.76 mu M. The lipopeptides inhibited the profile of K562 via three pathways: (1) induction of paraptosis indicated by the occurrence of cytoplasmic vacuoles, and swelling of the mitochondria and endoplasmic reticulum (ER) without membrane blebbing in the presence of a caspase inhibitor; (2) inhibition of autophagy progress illustrated by the upregulated expression of LCII and P62; and (3) induction of apoptosis by causing ROS burst, and induction of the intrinsic pathway indicated by the upregulated expression of cytochrome c (Cyto-c), bax, and bad, together with downregulated expression of Bcl-2. The ROS-dependent apoptosis and caspase-independent paraptosis were verified using the ROS inhibitor and caspase inhibitor, respectively. The extrinsic apoptosis pathway was not involved in the lipopeptide's effects on K562. Overall, the B. subtilis lipopeptides (consisting of a majority of iturin) exhibited promising potential in inhibiting chronic myelogenous leukemia in vitro via simultaneously causing paraptosis, apoptosis, and inhibition of autophagy.	[Zhao, Haobin; Yan, Lu; Xu, Xiaoguang; Jiang, Chunmei; Shi, Junling; Zhang, Yawen; Liu, Li; Lei, Shuzhen; Shao, Dongyan; Huang, Qingsheng] Northwestern Polytech Univ, Sch Life Sci, Key Lab Space Biosci & Biotechnol, 127 Youyi West Rd, Xian 710072, Shaanxi, Peoples R China		Shi, JL (corresponding author), Northwestern Polytech Univ, Sch Life Sci, Key Lab Space Biosci & Biotechnol, 127 Youyi West Rd, Xian 710072, Shaanxi, Peoples R China.	sjlshi2004@nwpu.edu.cn		Xu, Xiaoguang/0000-0001-9754-9857	National Key Technology RD ProgramNational Key Technology R&D Program [2015BAD16B02]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31471718, 1701722]; Modern Agricultural Industry Technology System [CARS-30]; Key research and development plan of Shaanxi Province [2017ZDXL-NY-0304]	This research was supported by the National Key Technology R&D Program (2015BAD16B02), the National Natural Science Foundation of China (Grant Nos. 31471718, 1701722), the Modern Agricultural Industry Technology System (CARS-30), and Key research and development plan of Shaanxi Province (2017ZDXL-NY-0304).	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J	Huang, YC; Hung, WC; Chye, SM; Chen, WT; Chai, CY				Huang, Ya-Chun; Hung, Wen-Chun; Chye, Soi-Moi; Chen, Wan-Tzu; Chai, Chee-Yin			para-Phenylenediamine-induced autophagy in human uroepithelial cell line mediated mutant p53 and activation of ERK signaling pathway	TOXICOLOGY IN VITRO			English	Article						para-Phenylenediamine; SV-HUC-1 cells; Autophagy; Mutant p53; Beclin-1	TUMOR-SUPPRESSOR P53; COLON-CANCER CELLS; P-PHENYLENEDIAMINE; PROTEIN-KINASE; DNA-DAMAGE; UP-REGULATION; MOUSE CELLS; INHIBITION; DEATH; BECLIN-1	para-Phenylenediamine (p-PD) is a major aromatic amine that is a widely used commercial oxidative-type hair dye. Some epidemiologic studies have suggested that the use of p-PD-based hair dyes might be related to increased risk of human malignant tumors including bladder cancer. However, the effects of p-PD on autophagy in human uroepithelial cells (SV-HUC-1) is still unclear. In this study, we demonstrate that p-PD can activate the extracellular signaling-regulated protein kinase 1/2 (ERK1/2) signaling pathway in SV-HUC-1 cells. In addition, we observed that autophagosomes increased in p-PD-treated SV-HUC-1 cells as shown by electron microscopy. Our results showed incremental increase of the concentrations, Beclin-1 and microtubule-associated protein light chain 3B (LC3B), which are important regulators of autophagosomes. In contrast, the MEK inhibitor (U0126) was suppressed autophagy and the effect of p-PD on ERK1/2, Beclin-1 and LC3B proteins expression, except for mutant p53. In this study, we demonstrated that inactivation of p53 induces a potent autophagy response. Finally, our results suggest that p-PD can activate the ERK1/2 signaling pathway and mutant p53, leading to the stimulation of autophagy in SV-HUC-1 cells. These results provide us with new insights for the understanding of the mechanism of p-PD-induced cell death in urothelial cells. (C) 2011 Elsevier Ltd. All rights reserved.	[Chen, Wan-Tzu; Chai, Chee-Yin] Kaohsiung Med Univ Hosp, Dept Pathol, Kaohsiung 807, Taiwan; [Huang, Ya-Chun; Chai, Chee-Yin] Kaohsiung Med Univ, Grad Inst Med, Coll Med, Kaohsiung, Taiwan; [Huang, Ya-Chun; Chai, Chee-Yin] Kaohsiung Med Univ, Dept Pathol, Coll Med, Kaohsiung, Taiwan; [Hung, Wen-Chun; Chai, Chee-Yin] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 80424, Taiwan; [Hung, Wen-Chun; Chai, Chee-Yin] Natl Sun Yat Sen Univ, Kaohsiung Med Univ Joint Res Ctr, Kaohsiung 80424, Taiwan		Chai, CY (corresponding author), Kaohsiung Med Univ Hosp, Dept Pathol, 100,Tzyou 1st Rd, Kaohsiung 807, Taiwan.	cychai@kmu.edu.tw		Chai, Chee-Yin/0000-0003-0486-9742	National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, Kaohsiung, Taiwan	This work was supported by a research grant from the National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, Kaohsiung, Taiwan.	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Vitro	DEC	2011	25	8					1630	1637		10.1016/j.tiv.2011.06.013			8	Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Toxicology	866EE	WOS:000298362500015	21741467				2022-04-25	
J	Ding, XF; Shen, M; Xu, LY; Dong, JH; Chen, G				Ding, Xiao-Fei; Shen, Mao; Xu, Li-Ying; Dong, Jin-Hua; Chen, Guang			13,14-bis(cis-3,5-dimethyl-1-piperazinyl)-beta-elemene, a novel beta-elemene derivative, shows potent antitumor activities via inhibition of mTOR in human breast cancer cells	ONCOLOGY LETTERS			English	Article						13,14-bis(cis-3,5-dimethyl-1-piperazinyl)-beta-elemene; beta-elemene; mTOR; autophagy; cancer	IN-VITRO; CARCINOMA	Elemene has been approved for the treatment of advanced cancer in China, however, it inhibits cell growth only at high concentrations and is an essential oil with poor water solubility and stability. The discovery of new beta-elemene derivatives is of increasing interest. We recently reported that the compound 13,14-bis(cis-3,5-dimethyl-1-piperazinyl)-beta-elemene (IIi), a novel beta-elemene derivative with a cis-2,6-dimethylpiperazine substitution, is a potent agent for inhibiting the proliferation of SGC-7901 and He La cells. In the present study, we further verified that Hi is cytotoxic to a wide spectrum of human cancer cells in culture, including those of breast, ovarian, lung, gastric, hepatocellular and colon cancer, as well as leukemia cell lines, with an average IC50 of 3.44 mu mol/l. Notably, m showed significant cytotoxicity in two multidrug-resistant (MDR) cell lines, with an average resistance factor (RF) of 1.66. Moreover, in mice with S-180 sarcoma xenografts, the intraperitoneal administration of Hi inhibited tumor growth. The immunoblotting study showed that treatment with IIi decreases phosphorylated p70S6K1 and 4EBP1 levels in the human breast cancer MCF-7 and MDA-MB-468 cells. In the MCF-7 cells, Ili also significantly increased the expression of cleaved LC3. This indicated that Hi inhibits mTOR activity and induces autophagy. The mTOR inhibitory function and the potent antitumor activity, taken together with the appreciable anti-multidrug resistance action, shows Ili to be a novel potential antitumor agent, which merits further research and development.	[Ding, Xiao-Fei] Taizhou Coll, Sch Med, Taizhou 318000, Zhejiang, Peoples R China; [Shen, Mao; Chen, Guang] Taizhou Coll, Sch Pharmaceut & Chem Engn, Taizhou 318000, Zhejiang, Peoples R China; [Xu, Li-Ying; Dong, Jin-Hua] Shenyang Pharmaceut Univ, Minist Educ, Key Lab Struct Based Drug Design & Discovery, Shenyang 110016, Liaoning, Peoples R China		Chen, G (corresponding author), Taizhou Coll, Sch Pharmaceut & Chem Engn, 1139 Shifu Ave, Taizhou 318000, Zhejiang, Peoples R China.	guang.yz.chen@gmail.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81201530]; Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [Y2110474, LY12H31001]	This study was supported by the National Natural Science Foundation of China (No. 81201530) and Zhejiang Provincial Natural Science Foundation of China (No. Y2110474 and LY12H31001).	Butler MS, 2004, J NAT PROD, V67, P2141, DOI 10.1021/np040106y; Carew Jennifer S, 2012, Cancer Manag Res, V4, P357, DOI 10.2147/CMAR.S26133; Guertin DA, 2007, CANCER CELL, V12, P9, DOI 10.1016/j.ccr.2007.05.008; Guo Y T, 1983, Zhong Yao Tong Bao, V8, P31; Hudes G, 2007, NEW ENGL J MED, V356, P2271, DOI 10.1056/NEJMoa066838; Kollmannsberger C, 1999, ONCOLOGY-BASEL, V56, P1, DOI 10.1159/000011923; Liu J, 2012, J PHARM PHARMACOL, V64, P146, DOI 10.1111/j.2042-7158.2011.01371.x; Ma XJM, 2009, NAT REV MOL CELL BIO, V10, P307, DOI 10.1038/nrm2672; Motzer RJ, 2008, LANCET, V372, P449, DOI 10.1016/S0140-6736(08)61039-9; National Cancer Institute, CANC STAT SEER STAT; Peng XX, 2006, CONTEMP CLIN TRIALS, V27, P70, DOI 10.1016/j.cct.2005.07.002; Qing C, 1999, ACTA PHARMACOL SIN, V20, P297; Tan P, 2000, Zhongguo Zhong Xi Yi Jie He Za Zhi, V20, P645; Tao L, 2006, CANCER CHEMOTH PHARM, V58, P24, DOI 10.1007/s00280-005-0137-x; Wan XL, 2007, ONCOLOGIST, V12, P1007, DOI 10.1634/theoncologist.12-8-1007; Wang J, 1996, Zhonghua Zhong Liu Za Zhi, V18, P464; WANI MC, 1971, J AM CHEM SOC, V93, P2325, DOI 10.1021/ja00738a045; World Health Organization, PROGR PROJ CANC BREA; Xu LY, 2006, BIOORGAN MED CHEM, V14, P5351, DOI 10.1016/j.bmc.2006.03.041	19	26	29	1	13	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1792-1074	1792-1082		ONCOL LETT	Oncol. Lett.	MAY	2013	5	5					1554	1558		10.3892/ol.2013.1213			5	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	136TE	WOS:000318385500022	23761818	gold, Green Published, Green Submitted			2022-04-25	
J	Rayner, KJ; Moore, KJ				Rayner, Katey J.; Moore, Kathryn J.			MicroRNA Control of High-Density Lipoprotein Metabolism and Function	CIRCULATION RESEARCH			English	Review						cholesterol; HDL; lipid metabolism; microRNAs	REVERSE CHOLESTEROL TRANSPORT; RAISES PLASMA HDL; LIPID-METABOLISM; TANGIER-DISEASE; CIRCULATING MICRORNAS; MICROBIOTA METABOLISM; ENDOTHELIAL-CELLS; ABCA1 EXPRESSION; COLON-CANCER; AUTOPHAGY	Recent discoveries of microRNAs (miRNAs) that control high-density lipoprotein abundance and function have expanded our knowledge of the mechanisms regulating this important lipoprotein subclass. miRNAs have been shown to regulate gene networks that control high-density lipoprotein biogenesis and uptake, as well as discrete steps in the reverse cholesterol transport pathway. Furthermore, high-density lipoprotein itself has been shown to transport miRNAs selectively in health and disease, offering new possibilities of how this lipoprotein may alter gene expression in distal target cells and tissues. Collectively, these discoveries offer new insights into the mechanisms governing high-density lipoprotein metabolism and function and open new avenues for the development of therapeutics for the treatment of cardiovascular disease.	[Rayner, Katey J.] Univ Ottawa, Inst Heart, Ottawa, ON, Canada; [Moore, Kathryn J.] NYU, Leon H Charney Div Cardiol, Dept Med, Marc & Ruti Bell Vasc Biol & Dis Program,Sch Med, New York, NY 10016 USA		Moore, KJ (corresponding author), NYU, Leon H Charney Div Cardiol, Dept Med, Sch Med, 522 First Ave,Smilow 705, New York, NY 10016 USA.	Kathryn.Moore@nyumc.org	Moore, Kathryn/ABE-6416-2020	Moore, Kathryn/0000-0003-2505-2547; Rayner, Katey/0000-0001-6230-426X	National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HL108182]; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR); NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL108182] Funding Source: NIH RePORTER	Research on microRNAs in the Moore Laboratory is supported by the National Institutes of Health (R01 HL108182). K.J. Rayner is supported by a Canadian Institutes of Health Research Operating Grant and Salary Award.	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JAN 3	2014	114	1					183	192		10.1161/CIRCRESAHA.114.300645			10	Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease	Science Citation Index Expanded (SCI-EXPANDED)	Cardiovascular System & Cardiology; Hematology	AG7GQ	WOS:000335586700023	24385511	Green Accepted, Bronze			2022-04-25	
J	Farooqi, AA; Naureen, H; Zahid, R; Youssef, L; Attar, R; Xu, BJ				Farooqi, Ammad Ahmad; Naureen, Humaira; Zahid, Rabbia; Youssef, Lara; Attar, Rukset; Xu, Baojun			Cancer chemopreventive role of fisetin: Regulation of cell signaling pathways in different cancers	PHARMACOLOGICAL RESEARCH			English	Review						Fisetin; Cancer prevention; Cell signaling pathway; PI3K/AKT/mTOR; Wnt/beta-catenin; TRAIL/TRAIL-R	DIETARY FLAVONOID FISETIN; NATURAL-PRODUCTS; BETA-CATENIN; COLON-CANCER; INDUCED APOPTOSIS; PROSTATE-CANCER; MESENCHYMAL TRANSITION; DRUG DISCOVERY; CYCLE ARREST; LUNG-CANCER	It is becoming progressively more understandable that pharmaceutical targeting of drug-resistant cancers is challenging because of intra- and inter-tumor heterogeneity. Interestingly, naturally derived bioactive compounds have unique ability to modulate wide-ranging deregulated oncogenic cell signaling pathways. In this review, we have focused on the available evidence related to regulation of PI3K/AKT/mTOR, Wnt/beta-catenin, NF-kappa B and TRAIL/TRAIL-R by fisetin in different cancers. Fisetin has also been shown to inhibit the metastatic spread of cancer cells in tumor-bearing mice. We have also summarized how fisetin regulated autophagy in different cancers. In addition, this review also covers fisetin-mediated regulation of VEGF/VEGFR, EGFR, necroptosis and Hippo pathway. Fisetin has entered into clinical trials particularly in context of COVID19-associated inflammations. Furthermore, fisetin mediated effects are also being tested in clinical trials with reference to osteoarthritis and senescence. These developments will surely pave the way for full-fledge and well-designed clinical trials of fisetin in different cancers. However, we still have to comprehensively analyze and fully unlock pharmacological potential of fisetin against different oncogenic signaling cascades and non-coding RNAs. Fisetin has remarkable potential as chemopreventive agent and future studies must converge on the identification of additional regulatory roles of fisetin for inhibition and prevention of cancers.	[Farooqi, Ammad Ahmad] Inst Biomed & Genet Engn IBGE, Dept Mol Oncol, Islamabad, Pakistan; [Naureen, Humaira] Riphah Int Univ, Fac Pharmaceut Sci, Islamabad, Pakistan; [Zahid, Rabbia] Univ Punjab, Inst Chem, Lahore, Pakistan; [Youssef, Lara] Univ Balamand UOB, Fac Med & Med Sci, Dept Biomed Sci, Al Kurah, Lebanon; [Attar, Rukset] Yeditepe Univ, Dept Obstet & Gynecol, Istanbul, Turkey; [Xu, Baojun] BNU HKBU United Int Coll, Food Sci & Technol Programme, Zhuhai, Peoples R China		Farooqi, AA (corresponding author), Inst Biomed & Genet Engn IBGE, Dept Mol Oncol, Islamabad, Pakistan.; Xu, BJ (corresponding author), BNU HKBU United Int Coll, Food Sci & Technol Programme, Zhuhai, Peoples R China.	Faeooqiammadahmad@gmail.com; baojunxu@uic.edu.cn	; Xu, Baojun/B-7971-2017	Youssef, Lara/0000-0003-3259-0706; Xu, Baojun/0000-0003-0739-3735	Beijing Normal University-Hong Kong Baptist University United International College [UIC202107];  [R5201911]	This project is jointly supported by one grant (project code: UIC202107) from Beijing Normal University-Hong Kong Baptist University United International College and one research grant from Guangdong Education Bureau (Project code: R5201911).	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Res.	OCT	2021	172								105784	10.1016/j.phrs.2021.105784		AUG 2021	11	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	UR3UW	WOS:000696677900005	34302980				2022-04-25	
J	Kar, R; Singha, PK; Venkatachalam, MA; Saikumar, P				Kar, R.; Singha, P. K.; Venkatachalam, M. A.; Saikumar, P.			A novel role for MAP1 LC3 in nonautophagic cytoplasmic vacuolation death of cancer cells	ONCOGENE			English	Article						cell death; cytoplasmic vacuolation; LC3; ER stress; MAPK; 15d-PGJ2	15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); OXIDATIVE STRESS; INDUCE APOPTOSIS; DRUG-RESISTANCE; DNA-BINDING; AUTOPHAGY; ACTIVATION; MECHANISMS; PROTEASOME; INHIBITION	Thiol reactive cyclopentenone prostaglandin, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ2), induced a novel, nonapoptotic and microtubule-associated protein 1 light chain 3 (MAP1 LC3) dependent but nonautophagic form of cell death in colon, breast and prostate cancer cell lines, characterized by extensive cytoplasmic vacuolation with dilatation of endoplasmic reticulum (ER). Disruption of sulfhydryl homeostasis, which resulted in ER stress, accumulation of ubiquitinated proteins and subsequent ER dilation, contributed to peroxisome proliferator-activated receptor gamma (PPAR gamma)-independent cell death by 15d-PGJ2. Absence of intracellular organelles in these vacuoles, shown by electron microscopy and unique fragmentation of lamin B, suggested this form of cell death to be different from autophagy and apoptosis. Cell death induced by 15d-PGJ2 is prevented by cycloheximide and actinomycin D, suggesting a requirement of new protein synthesis for death with cytoplasmic vacuolation. Here, we report for the. first time that upregulation and processing of autophagy marker LC3 is an important event in nonautophagic cytoplasmic vacuolation and cell death. Notably, knockdown of LC3 conferred significant protection against 15d-PGJ2-induced cytoplasmic vacuolation and cell death, suggesting a novel role of LC3 in a death process other than autophagy. Oncogene (2009) 28, 2556-2568; doi: 10.1038/onc.2009.118; published online 18 May 2009	[Kar, R.; Singha, P. K.; Venkatachalam, M. A.; Saikumar, P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA		Saikumar, P (corresponding author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.	saikumar@uthscsa.edu			National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK54472, DK37139]; Morrison Trust; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01DK037139, R01DK054472, R37DK037139] Funding Source: NIH RePORTER	We thank Dr Tamotsu Yoshimori of Osaka University, Japan, for LC3 antibody and GFP-LC3 construct and Drs Anthony J Valente and Robert A Clark of UTHSCSA, TX, for Calreticulin antibody. This work was supported by National Institutes of Health grant DK54472 and Morrison Trust Grant to PS and National Institutes of Health grant DK37139 to MAV.	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J	Zang, XL; Cheng, MY; Zhang, XX; Chen, XH				Zang, Xinlong; Cheng, Mingyang; Zhang, Xiaoxu; Chen, Xuehong			Quercetin nanoformulations: a promising strategy for tumor therapy	FOOD & FUNCTION			English	Review							MESOPOROUS SILICA NANOPARTICLES; COLON-CANCER CELLS; BREAST-CANCER; MULTIDRUG-RESISTANCE; OXIDE NANOPARTICLES; ANTITUMOR-ACTIVITY; TARGETED DELIVERY; LUNG METASTASIS; IN-VITRO; APOPTOSIS	Phytochemicals as dietary constituents are being widely explored for the prevention and treatment of various diseases. Quercetin, a major constituent of various dietary products, has attracted extensive interest due to its anti-proliferative capability, reversal of multidrug resistance, autophagy promotion and tumor microenvironment modulation on different cancer types. Although quercetin has shown potent medical value, its application as an antitumor drug is limited. Problems like poor solubility, bioavailability and stability, short half-life and weak tumor-targeting biodistribution make quercetin an unreliable candidate for cancer therapy. Nanoparticle based platforms have shown a number of advantages in delivering a hydrophobic drug like quercetin to diseased tissues. Quercetin nanoparticles have demonstrated high encapsulation efficiency, stability, sustained release, prolonged circulation time, improved accumulation at tumor sites and therapeutic efficiency. Moreover, a combination of quercetin with other diagnostic or therapeutic agents in one nanocarrier has achieved enhancements in detecting or treating tumors. In this review, we have tried to summarize the pharmacological activities of quercetin with regard to tumor cells and microenvironments in vitro and in vivo. Furthermore, various nanoformulations have been highlighted for quercetin delivery for cancer treatment. These results suggest that quercetin nanoparticles may be a promising antitumor therapeutic agent.	[Zang, Xinlong; Cheng, Mingyang; Zhang, Xiaoxu; Chen, Xuehong] Qingdao Univ, Sch Basic Med, Ningxia Rd 308, Qingdao, Peoples R China		Zang, XL (corresponding author), Qingdao Univ, Sch Basic Med, Ningxia Rd 308, Qingdao, Peoples R China.	zangxinlong@126.com		chen, xuehong/0000-0003-0102-4023; zang, xinlong/0000-0002-9250-2782	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [82003676]	This work is funded by the National Natural Science Foundation of China (82003676).	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AUG 7	2021	12	15					6664	6681		10.1039/d1fo00851j		JUN 2021	18	Biochemistry & Molecular Biology; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Food Science & Technology	TX5GO	WOS:000663885300001	34152346				2022-04-25	
J	Luo, SL; Li, ZY; Mao, LZ; Chen, SQ; Sun, SX				Luo, Shunli; Li, Ziyin; Mao, Lianzhi; Chen, Siqiang; Sun, Suxia			Sodium butyrate induces autophagy in colorectal cancer cells through LKB1/AMPK signaling	JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY			English	Article						Sodium butyrate; Autophagy; Colorectal cancer; Liver kinase B1 (LKB1); AMP-activated protein kinase (AMPK)	MEDIATED APOPTOSIS; DEPENDENT MANNER; RECENT PROGRESS; PATHWAY; CARCINOMA; METABOLISM; ACTIVATION; LKB1; ACETYLATION; EXPRESSION	Butyrate is produced by the fermentation of undigested dietary fibers and acts as the promising candidate for cancer treatment. However, the mechanism underlying sodium butyrate (NaB)-induced autophagy in colorectal cancer is not yet completely understood. The expressions of LC3-II protein and mRNA were detected by western blot and quantitative RT-PCR in colorectal cancer (CRC) cell lines HCT-116 and HT-29, respectively. Autolysosome formation was observed by transmission electron microscope. AMPK and LKB1 were inhibited by chemical inhibitor or siRNAs and confirmed by western blot. NaB elevated the protein and mRNA expressions of LC3 in a dose-dependent manner. NaB treatment increased the formation of autolysosome and expression of phosphorylated liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC). Treatment with compound C (an inhibitor of AMPK) and siRNA-mediated knockdown of AMPK and LKB1 significantly attenuated NaB-induced autophagy in CRC cells. Collectively, these findings indicated that LKB1 and AMPK are critical for NaB-mediated autophagy and may act as the novel targets for colorectal cancer therapy in the future.	[Luo, Shunli; Li, Ziyin; Mao, Lianzhi; Sun, Suxia] Southern Med Univ, Dept Nutr & Food Hyg, Guangdong Prov Key Lab Trop Dis Res, Sch Publ Hlth, 1023 South Sha Tai Rd, Guangzhou 510515, Guangdong, Peoples R China; [Luo, Shunli] Hunan Univ Med, Sch Lab Med, Huaihua 418000, Peoples R China; [Chen, Siqiang] Guangzhou Customs Dist, 66 Huacheng Ave, Guangzhou 510623, Guangdong, Peoples R China		Sun, SX (corresponding author), Southern Med Univ, Dept Nutr & Food Hyg, Guangdong Prov Key Lab Trop Dis Res, Sch Publ Hlth, 1023 South Sha Tai Rd, Guangzhou 510515, Guangdong, Peoples R China.	suxia.sun@yale.edu		Sun, Suxia/0000-0002-1159-6191; Mao, Lianzhi/0000-0003-1153-0990	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81773429, 81202204]; Guangdong National Natural Science Foundation [S2012010009467]; Project for Excellent Young University Teacher award	This study was supported by the grants from National Natural Science Foundation of China (No. 81773429 and 81202204), Guangdong National Natural Science Foundation (No. S2012010009467), Project for Excellent Young University Teacher awarded to Southern Medical University.	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Physiol. Biochem.	FEB	2019	75	1					53	63		10.1007/s13105-018-0651-z			11	Biochemistry & Molecular Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Physiology	HO2PB	WOS:000460756300006	30362049				2022-04-25	
J	Sivridis, E; Koukourakis, MI; Zois, CE; Ledaki, I; Ferguson, DJP; Harris, AL; Gatter, KC; Giatromanolaki, A				Sivridis, Efthimios; Koukourakis, Michael I.; Zois, Christos E.; Ledaki, Ioanna; Ferguson, David J. P.; Harris, Adrian L.; Gatter, Kevin C.; Giatromanolaki, Alexandra			LC3A-Positive Light Microscopy Detected Patterns of Autophagy and Prognosis in Operable Breast Carcinomas	AMERICAN JOURNAL OF PATHOLOGY			English	Article							NUTRIENT DEPRIVATION; MOLECULAR MACHINERY; TUMOR ANGIOGENESIS; PANCREATIC-CANCER; INDUCED APOPTOSIS; ATG9 TRAFFICKING; MAMMARY-GLAND; HYPOXIA; BECLIN-1; PROTEIN	Autophagy is a self-degradation mechanism by which cells recycle their own cytoplasmic constituents and dispose of excess or defective organelles after starvation and oxygen deprivation. An antibody to the microtubule-associated protein 1 light chain 3 (LC3A), recognizing both the soluble (LC3A-I) and the membrane-bound form (LC3A-II) of the protein, was used to detect autophagic activity in 102 breast carcinomas. Three distinct patterns were recognized: (1) diffuse cytoplasmic, (2) cytoplasmic/juxta-nuclear, and (3) "stone-like" pattern - dense, rounded, amorphous structures, 5 mu m on average, typically enclosed within cytoplasmic vacuoles. The diffuse cytoplasmic pattern showed a direct association with estrogen and progesterone receptor expression. The juxta-nuclear pattern indicated a similar association with hormone receptors, an inverse association with tumor size, and a favorable prognosis. By contrast, an increased number of stonelike structures, probably representing an excessive autophagic response, was related to high-grade tumors and a less favorable outcome. Interestingly, 60 additional epithelial tumors of nonbreast origin disclosed identical autophagic patterns, and so did MDA231 breast cancer xenografts and HCT116 colon tumor spheroids (also analyzed by electron microscopy). Moreover, MCF-7 human breast cancer cell lines confirmed induction of LC3A by anoxia and Thapsigargin. It is concluded that autophagy can be readily recognized in breast carcinomas by light microscopy, after immunohistochemical staining with LC3A, but the significance of the various patterns expressed would need further evaluation. (Am J Pathol 2010, 176:2477-2489; DOI: 10.2353/ajpath.2010.090049)	[Sivridis, Efthimios; Giatromanolaki, Alexandra] Democritus Univ Thrace, Dept Pathol, Alexandroupolis 68100, Greece; [Koukourakis, Michael I.; Zois, Christos E.] Democritus Univ Thrace, Dept Radiotherapy Oncol, Alexandroupolis 68100, Greece; Univ Gen Hosp Alexandroupolis, Alexandroupolis, Greece; [Ledaki, Ioanna; Ferguson, David J. P.; Harris, Adrian L.; Gatter, Kevin C.] Univ Oxford, John Radcliffe Hosp, Canc Res UK, Weatherall Inst Mol Med,Mol Oncol Labs, Oxford OX3 9DU, England; Univ Oxford, John Radcliffe Hosp, Dept Clin Lab Sci, Oxford OX3 9DU, England		Giatromanolaki, A (corresponding author), Democritus Univ Thrace, Dept Pathol, Alexandroupolis 68100, Greece.	agiatrom@med.duth.gr	Harris, Adrian/ABA-3343-2020	Harris, Adrian/0000-0003-1376-8409; Ferguson, David/0000-0001-5045-819X	Tumor and Angiogenesis Research Group; Cancer Research, UKCancer Research UK; Oxford NIHR	Supported by the Tumor and Angiogenesis Research Group, the Cancer Research, UK, and the Oxford NIHR Biomedical Research Center Programme.	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J. Pathol.	MAY	2010	176	5					2477	2489		10.2353/ajpath.2010.090049			13	Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Pathology	627XV	WOS:000280078600042	20382705	Green Published, Bronze			2022-04-25	
J	Figueroa-Gonzalez, G; Garcia-Castillo, V; Coronel-Hernandez, J; Lopez-Urrutia, E; Leon-Cabrera, S; Arias-Romero, LE; Terrazas, LI; Rodriguez-Sosa, M; Campos-Parra, AD; Zuniga-Calzada, E; Lopez-Camarillo, C; Morales-Gonzalez, F; Jacobo-Herrera, NJ; Perez-Plasencia, C				Figueroa-Gonzalez, Gabriela; Garcia-Castillo, Veronica; Coronel-Hernandez, Jossimar; Lopez-Urrutia, Eduardo; Leon-Cabrera, Sonia; Arias-Romero, Luis E.; Terrazas, L. I.; Rodriguez-Sosa, Miriam; Delia Campos-Parra, Alma; Zuniga-Calzada, Eduardo; Lopez-Camarillo, Cesar; Morales-Gonzalez, Fermin; Jacobo-Herrera, Nadia J.; Perez-Plasencia, Carlos			Anti-inflammatory and Antitumor Activity of a Triple Therapy for a Colitis-Related Colorectal Cancer	JOURNAL OF CANCER			English	Article						Colorectal Cancer; Chronic Inflammation; Glycolysis; mTOR; Autophagy	LACTATE-DEHYDROGENASE; LDH-A; METFORMIN; DOXORUBICIN; INFLAMMATION; INHIBITION; RESISTANCE; RECEPTOR; GROWTH	Colorectal cancer (CRC) is an important health issue worldwide, accounting for the third place of cancer incidence. Chronic inflammation, as seen in Crohn's disease and ulcerative colitis, is the most important risk factor for developing CRC, as it favours neoplastic transformation by enhancing epithelial cell turnover in the colonic mucosa. Treatments for CRC need to be improved; currently they are not specific and have several secondary effects in patients. The main objective of this work was to evaluate a new therapeutic strategy against a colitis-related colorectal cancer in vivo and in vitro by targeting mTOR-signaling and lactate dehydrogenase A. Together, these mechanisms directly affect tumor energetics. In this study we evaluated a better and more efficient triple therapy against a chronic inflammation-associated CRC in vivo and in vitro. After the development of tumors, mice were treated intraperitoneally during a forty-day period with single drugs or different combinations of Metformin, Sodium Oxamate and Doxorubicin. Targeted inhibition of the mTOR pathway, lactate dehydrogenase A and the concurrent use of Doxorubicin (called in this work as triple therapy), leaded to a notable reduction in the number and size of tumors in mice, and, a significant pro-inflammatory cytokines reduction Besides, we showed that treated cells were induced to early autophagy, and apoptosis cell death. Our results represent a novel and robust therapeutic strategy for overcoming CRC by means of targeting central molecular pathways in cancer by the combination of Metformin, Oxamate, and Doxorubicin leading to a rapid tumor growth inhibition and a dramatic colorectal crypt restoration. Besides, drug combination resulted in a notable reduction of anti-inflammatory cytokines.	[Figueroa-Gonzalez, Gabriela; Garcia-Castillo, Veronica; Coronel-Hernandez, Jossimar; Lopez-Urrutia, Eduardo; Leon-Cabrera, Sonia; Arias-Romero, Luis E.; Terrazas, L. I.; Rodriguez-Sosa, Miriam; Perez-Plasencia, Carlos] Univ Nacl Autonoma Mexico, Unidad Biomed, FES Iztacala, Av Los Barrios, Tlalnepantla 54090, Estado De Mexic, Mexico; [Figueroa-Gonzalez, Gabriela; Delia Campos-Parra, Alma; Perez-Plasencia, Carlos] Inst Nacl Cancerol, Lab Genom, Direcc Invest, Av San Fernando 22,Secc 16, Mexico City 14080, DF, Mexico; [Leon-Cabrera, Sonia] Univ Nacl Autonoma Mexico, Carrera Med Cirujano, FES Iztacala, Av Los Barrios, Tlalnepantla 54090, Estado De Mexic, Mexico; [Zuniga-Calzada, Eduardo] Inst Nacl Seguridad Social Estado Mexico & Munici, Dept Anat Patol, Ave Trabajo S-N, Ecatepec De Morelos 55000, Estado De Mexic, Mexico; [Lopez-Camarillo, Cesar] UACM, Programa Ciencias Genom, Mexico City, DF, Mexico; [Morales-Gonzalez, Fermin] Inst Jalisciense Cancerol, Direcc Med, Coronel Calderon 715, Guadalajara 44280, Jalisco, Mexico; [Jacobo-Herrera, Nadia J.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Bioquim, Vasco de Quiroga 15,Secc 16, Mexico City 14000, DF, Mexico		Perez-Plasencia, C (corresponding author), Univ Nacl Autonoma Mexico, Unidad Biomed, FES Iztacala, Av Los Barrios, Tlalnepantla 54090, Estado De Mexic, Mexico.; Perez-Plasencia, C (corresponding author), Inst Nacl Cancerol, Lab Genom, Direcc Invest, Av San Fernando 22,Secc 16, Mexico City 14080, DF, Mexico.; Jacobo-Herrera, NJ (corresponding author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Bioquim, Vasco de Quiroga 15,Secc 16, Mexico City 14000, DF, Mexico.	nadia.jacobo@gmail.com; carlos.pplas@gmail.com	Terrazas, Luis I/AAV-8858-2020; Lopez-Urrutia, Eduardo/N-7360-2019; Jacobo-Herrera, Nadia/AGG-8009-2022; Figueroa, Gabriela/ABD-1060-2021; Perez-Plasencia, Carlos/P-2372-2019; Leon-Cabrera, Sonia/L-6596-2019; Lopez-Camarillo, Cesar/I-1946-2019	Lopez-Urrutia, Eduardo/0000-0002-5307-2003; Jacobo-Herrera, Nadia/0000-0002-1026-3774; Figueroa, Gabriela/0000-0001-8169-4478; Perez-Plasencia, Carlos/0000-0002-8593-8211; Leon-Cabrera, Sonia/0000-0002-1661-5013; Lopez-Camarillo, Cesar/0000-0002-9417-2609; Arias-Romero, Luis E./0000-0001-5676-2483; Campos-Parra, Alma D./0000-0003-1750-5171; Coronel-Hernandez, Jossimar/0000-0001-6543-5310; GARCIA, VERONICA/0000-0002-8726-1224; Terrazas, Luis I./0000-0003-1635-9467	Direccion General de Asuntos del Personal Academico	G. F-G. Is grateful to Direccion General de Asuntos del Personal Academico for a postdoctoral scholarship.	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Cancer		2016	7	12					1632	1644		10.7150/jca.13123			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EJ2YB	WOS:000393076400007	27698900	Green Published, Green Submitted, gold			2022-04-25	
J	Mazouffre, C; Geyl, S; Perraud, A; Blondy, S; Jauberteau, MO; Mathonnet, M; Verdier, M				Mazouffre, Clement; Geyl, Sophie; Perraud, Aurelie; Blondy, Sabrina; Jauberteau, Marie-Odile; Mathonnet, Muriel; Verdier, Mireille			Dual inhibition of BDNF/TrkB and autophagy: a promising therapeutic approach for colorectal cancer	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE			English	Article						colorectal cancer; neurotrophins; autophagy; therapy	KINASE-B; RECEPTOR; ACTIVATION; CONTRIBUTES; CHLOROQUINE; EXPRESSION; RESISTANCE; RELEVANCE; APOPTOSIS; PATHWAY	Colorectal cancer (CRC) is the most common digestive cancer in the Western world. Despite effective therapies, resistance and/or recurrence frequently occur. The present study investigated the impact of two survival pathwaysneurotrophic factors (TrkB/BDNF) and autophagyon cell fate and tumour evolution. In vitro studies were performed on two CRC cell lines, SW480 (primary tumour) and SW620 (lymph node invasion), which were also used for subcutaneous xenografts on a nude mouse model. In addition, the presence of neurotrophic factors (NTs) and autophagy markers were assessed in tissue samples representative of different stages. On the basis of our previous study (which demonstrated that TrkB overexpression is associated with prosurvival signaling in CRC cells), we pharmacologically inhibited NTs pathways with K252a. As expected, an inactivation of the PI3K/AKT pathway was observed and CRC cells initiated autophagy. Conversely, blocking the autophagic flux with chloroquine or with ATG5-siRNA overactivated TrkB/BDNF signaling. In vitro, dual inhibition improved the effectiveness of single treatment by significantly reducing metabolic activity and enhancing apoptotic cell death. These findings were accentuated in vivo, in which dual inhibition induced a spectacular reduction in tumour volume following long-term treatment (21 days for K252a and 12 days for CQ). Finally, significant amounts of phospho-TrkB and LC3II were found in the patients' tissues, highlighting their relevance in CRC tumour biology. Taken together, our results show that targeting NTs and autophagy pathways potentially constitutes a new therapeutic approach for CRC.	[Mazouffre, Clement; Geyl, Sophie; Perraud, Aurelie; Blondy, Sabrina; Jauberteau, Marie-Odile; Mathonnet, Muriel; Verdier, Mireille] Univ Limoges, Fac Med & Pharm, Homeostasie Cellulaire & Pathol, Lab EA 3842, Limoges, France; [Perraud, Aurelie; Mathonnet, Muriel] CHU Limoges, Serv Chirurg Digest Gen & Endocrinienne, Limoges, France		Verdier, M (corresponding author), Univ Limoges, Fac Med & Pharm, Homeostasie Cellulaire & Pathol, Lab EA 3842, Limoges, France.	mireille.verdier@unilim.fr	Mathonnet, Muriel/ABD-3021-2020	Mathonnet, Muriel/0000-0002-9127-3068; Jauberteau, Marie-Odile/0000-0002-8811-8948; VERDIER, Mireille/0000-0002-8162-4856; Perraud, Aurelie/0000-0001-7882-0613	Conseil Regional du LimousinRegion Nouvelle-Aquitaine; Agence Regionale de Sante Limousin (ARS); La Ligue Contre le Cancer (Comite du Limousin); Le Comite d'Orientation de la Recherche sur le Cancer (CORC) en Limousin	C.M. received a fellowship from the Conseil Regional du Limousin and S.G. received a fellowship from the Agence Regionale de Sante Limousin (ARS). Additional financial support was provided by La Ligue Contre le Cancer (Comite du Limousin) and by Le Comite d'Orientation de la Recherche sur le Cancer (CORC) en Limousin. The funding institutions had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Autors are grateful to the Anatomopathology department from the Limoges' Hospital for histological and immunohistochemical support, and to Michelle Nouailles for patients'informations. C.M., S.G., A.P. and S.B. performed the research; M.O.J., M.M. and M.V. designed the research study; M.M. and M.V. analysed the data; C.M., S.G., A.P. and M.V. wrote the paper.	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Cell. Mol. Med.	OCT	2017	21	10					2610	2622		10.1111/jcmm.13181			13	Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Research & Experimental Medicine	FI3OV	WOS:000411875400033	28597984	Green Published, gold			2022-04-25	
J	Chiacchiera, F; Matrone, A; Ferrari, E; Ingravallo, G; Lo Sasso, G; Murzilli, S; Petruzzelli, M; Salvatore, L; Moschetta, A; Simone, C				Chiacchiera, F.; Matrone, A.; Ferrari, E.; Ingravallo, G.; Lo Sasso, G.; Murzilli, S.; Petruzzelli, M.; Salvatore, L.; Moschetta, A.; Simone, C.			p38 alpha blockade inhibits colorectal cancer growth in vivo by inducing a switch from HIF1 alpha- to FoxO-dependent transcription	CELL DEATH AND DIFFERENTIATION			English	Article						p38 alpha; autophagy; FoxO; HIF1 alpha; colorectal cancer cell metabolism	ACTIVATED PROTEIN-KINASE; AUTOPHAGIC CELL-DEATH; MAP KINASE; P38; HYPOXIA; PHOSPHORYLATION; PATHWAYS; CARCINOGENESIS; PROLIFERATION; METABOLISM	Colorectal cancer cell (CRC) fate is governed by an intricate network of signaling pathways, some of which are the direct target of DNA mutations, whereas others are functionally deregulated. As a consequence, cells acquire the ability to grow under nutrients and oxygen shortage conditions. We earlier reported that p38 alpha activity is necessary for proliferation and survival of CRCs in a cell type-specific manner and regardless of their phenotype and genotype. Here, we show that p38 alpha sustains the expression of HIF1 alpha target genes encoding for glycolytic rate-limiting enzymes, and that its inhibition causes a drastic decrease in ATP intracellular levels in CRCs. Prolonged inactivation of p38 alpha triggers AMPK-dependent nuclear localization of FoxO3A and subsequent activation of its target genes, leading to autophagy, cell cycle arrest and cell death. In vivo, pharmacological blockade of p38 alpha inhibits CRC growth in xenografted nude mice and azoxymethane-treated Apc(Min) mice, achieving both a cytostatic and cytotoxic effect, associated with high nuclear expression of FoxO3A and increased expression of its target genes p21 and PTEN. Hence, inhibition of p38 alpha affects the aerobic glycolytic metabolism specific of cancer cells and might be taken advantage of as a therapeutic strategy targeted against CRCs. Cell Death and Differentiation (2009) 16, 1203-1214; doi: 10.1038/cdd.2009.36; published online 3 April 2009	[Chiacchiera, F.; Matrone, A.; Ferrari, E.; Simone, C.] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Translat Pharmacol, Lab Signal Dependent Transcript, I-66030 Santa Maria Imbaro, Ch, Italy; [Ingravallo, G.] Univ Bari, Dept Pathol Anat, I-70124 Bari, Italy; [Lo Sasso, G.; Murzilli, S.; Petruzzelli, M.; Salvatore, L.; Moschetta, A.] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Translat Pharmacol, Lab Lipid Metab & Canc, I-66030 Santa Maria Imbaro, Ch, Italy; [Petruzzelli, M.; Moschetta, A.] Univ Bari, Clin Med Murri, Dept Internal & Publ Med, I-70124 Bari, Italy		Simone, C (corresponding author), Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Translat Pharmacol, Lab Signal Dependent Transcript, Via Nazl 8A, I-66030 Santa Maria Imbaro, Ch, Italy.	simone@negrisud.it	Ingravallo, Giuseppe/Q-1477-2016; Simone, Cristiano/K-3452-2018; Chiacchiera, Fulvio/K-6740-2016; INGRAVALLO, Giuseppe/N-2466-2019; Moschetta, Antonio/K-6211-2016; Moschetta, Antonio/AAC-5295-2022; Chiacchiera, Fulvio/ABD-6137-2020	Ingravallo, Giuseppe/0000-0002-4792-3545; Simone, Cristiano/0000-0002-2628-7658; Chiacchiera, Fulvio/0000-0003-3830-2090; INGRAVALLO, Giuseppe/0000-0002-4792-3545; Moschetta, Antonio/0000-0003-2123-6074	FIRC (Italian Foundation for Cancer Research)Fondazione AIRC per la ricerca sul cancro; AIRC (Italian Association for Cancer Research)Fondazione AIRC per la ricerca sul cancro; Fondazione Negri Sud ONLUS	We thank Dr. Francesco Paolo Jori for his helpful discussion during the preparation of the manuscript and editorial assistance and Dr. Nicola Martelli for technical assistance. Dr. Chiacchiera and Dr. Matrone are supported by FIRC (Italian Foundation for Cancer Research) and AIRC (Italian Association for Cancer Research) fellowships, respectively.; This work was partially supported by a 'My First Grant' (to CS) and a 'Start-Up Grant' (to AM) from the Italian Association for Cancer Research and by a grant from 'Fondazione Negri Sud ONLUS' (to CS). CS is grateful to his wife Viviana for continuous encouragement and support.	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SEP	2009	16	9					1203	1214		10.1038/cdd.2009.36			12	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	484NY	WOS:000269054200003	19343039	Green Published, Bronze			2022-04-25	
J	Tatebayashi, D; Himori, K; Yamada, R; Ashida, Y; Miyazaki, M; Yamada, T				Tatebayashi, Daisuke; Himori, Koichi; Yamada, Ryotaro; Ashida, Yuki; Miyazaki, Mitsunori; Yamada, Takashi			High-intensity eccentric training ameliorates muscle wasting in colon 26 tumor-bearing mice	PLOS ONE			English	Article							HUMAN SKELETAL-MUSCLE; MYOSIN HEAVY-CHAIN; PARENTERAL-NUTRITION; CANCER; ATROPHY; CACHEXIA; ACTIVATION; EXPRESSION; AUTOPHAGY; EXERCISE	Eccentric (ECC) contractions are used to maintain skeletal muscle mass and strength in healthy subjects and patients. Here we investigated the effects of ECC training induced by electrical stimulation (ES) on muscle wasting in colon 26 (C-26) tumor-bearing mice. Mice were divided into four groups: control (CNT), CNT + ECC, C-26, and C-26 + ECC. Cancer cachexia was induced by a subcutaneous injection of C-26 cells and developed for four weeks. In experiment 1, muscle protein synthesis rate and mammalian target of rapamycin complex (mTORC) 1 signaling were investigated six hours after one bout of ECC-ES (2 s contraction given every 6 s, 20 degrees/s, 4 sets of 5 contractions). In experiment 2, ECC-ES training, a total of 14 sessions, was performed every other day starting one day after C-26 injection. Compared to the CNT mice, the gastrocnemius muscle weight was significantly decreased in the tumor-bearing mice. This change was accompanied by a reduction in protein synthesis rate and a marked increase in the expression levels of genes including regulated in development and DNA damage responses (REDD) 1, forkhead box protein 01 (FoxO1), muscle-specific E3 ubiquitin ligases atrogin-1, and muscle ring finger 1 (MuRF-1) mRNA. ECC-ES increased the protein synthesis rate and the phosphorylation levels of p70S6K (Thr389) and rpS6 (Ser240/244), markers for mTORC1 signaling, and reversed an upregulation of MuRF-1 mRNA in muscles from C-26 mice. Our findings suggest that ECC-ES training reduces skeletal muscle atrophy in C-26 tumor-bearing mice through activation of mTORC1 signaling and the inhibition of ubiquitin-proteasome pathway. Thus, ECC-ES training might be used to effectively ameliorate muscle wasting in patients with cancer cachexia.	[Tatebayashi, Daisuke; Himori, Koichi; Yamada, Ryotaro; Ashida, Yuki; Yamada, Takashi] Sapporo Med Univ, Grad Sch Hlth Sci, Sapporo, Hokkaido, Japan; [Miyazaki, Mitsunori] Hlth Sci Univ Hokkaido, Sch Rehabil Sci, Tobetsu, Japan		Yamada, T (corresponding author), Sapporo Med Univ, Grad Sch Hlth Sci, Sapporo, Hokkaido, Japan.	takashi.yamada1976@sapmed.ac.jp	Yamada, Takashi/U-8443-2019; Yamada, Takashi/AAZ-6212-2021; Miyazaki, Mitsunori/AAM-8598-2021	Yamada, Takashi/0000-0003-1797-3880; Yamada, Takashi/0000-0003-1797-3880; Miyazaki, Mitsunori/0000-0001-7824-2091	Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [50583176]	This study was supported by grants from the Japan Society for the Promotion of Science (No. 50583176).	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J	Le, DDT; Jung, S; Quynh, NTN; Sandag, Z; Lee, BS; Kim, S; Lee, H; Lee, H; Lee, MS				Dan-Diem Thi Le; Jung, Samil; Nguyen Thi Ngoc Quynh; Sandag, Zolzaya; Lee, Beom Suk; Kim, Subeen; Lee, Hyegyeong; Lee, Hyojeong; Lee, Myeong-Sok			Inhibitory role of AMP-activated protein kinase in necroptosis of HCT116 colon cancer cells with p53 null mutation under nutrient starvation	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						necroptosis; p53; AMP-activated protein kinase	PERMEABILITY TRANSITION; PROGRAMMED NECROSIS; INTRACELLULAR ATP; TARGETING AMPK; NECROTIC DEATH; COMPOUND C; APOPTOSIS; TOLERANCE; AUTOPHAGY; SURVIVAL	Simultaneous induction of other types of programmed cell death, alongside apoptosis, in cancer cells may be considered an attractive strategy for the development of more effective anticancer therapies. The present study aimed to investigate the role of AMP-activated protein kinase (AMPK) in nutrient/serum starvation-induced necroptosis, which is a programmed form of necrosis, in the presence or absence of p53. The present study detected higher cell proliferation and lower cell death rates in the HCT116 human colon cancer cell line containing a p53 null mutation (HCT116 p53(-/-)) compared with in HCT116 cells harboring wild-type p53 (HCT116 p53(+/+)), as determined using a cell viability assay. Notably, western blot analysis revealed a relatively lower level of necroptosis in HCT116 p53(-/-) cells compared with in HCT116 p53(+/+) cells. Investigating the mechanism, it was revealed that necroptosis may be induced in HCT116 p53(+/+) cells by significantly increasing reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP), whereas little alterations were detected in HCT116 p53(-/-) cells. Unexpectedly, a much lower level of ATP was detected in HCT116 p53(-/-) cells compared with in HCT116 p53(+/+) cells. Accordingly, AMPK phosphorylation on the Thr172 residue was markedly increased in HCT116 p53(-/-) cells. Furthermore, western blot analysis and ROS measurements indicated that AMPK inhibition, using dorsomorphin dihydrochloride, accelerated necroptosis by increasing ROS generation in HCT116 p53(-/-) cells. However, AMPK activation by AICAR did not suppress necroptosis in HCT116 p53(+/+) cells. In conclusion, these data strongly suggested that AMPK activation may be enhanced in HCT116 p53(-/-) cells under serum-depleted conditions via a drop in cellular ATP levels. In addition, activated AMPK may be at least partially responsible for the inhibition of necroptosis in HCT116 p53(-/-) cells, but not in HCT116 p53(+/+)cells.	[Dan-Diem Thi Le; Jung, Samil; Nguyen Thi Ngoc Quynh; Sandag, Zolzaya; Lee, Beom Suk; Kim, Subeen; Lee, Hyegyeong; Lee, Hyojeong; Lee, Myeong-Sok] Sookmyung Womens Univ, Dept Biol Sci, 100 Cheongpa Ro 47 Gil, Seoul 04310, South Korea		Lee, MS (corresponding author), Sookmyung Womens Univ, Dept Biol Sci, 100 Cheongpa Ro 47 Gil, Seoul 04310, South Korea.	mslee@sookmyung.ac.kr			Sookmyung Women's University	The present study was supported by Sookmyung Women's University (2015).	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J	Kumari, N; Bansal, S				Kumari, Neha; Bansal, Saurabh			Arginine depriving enzymes: applications as emerging therapeutics in cancer treatment	CANCER CHEMOTHERAPY AND PHARMACOLOGY			English	Review						Auxotrophic cancer; Argininosuccinate synthetase; Therapeutic enzyme; Deprivation therapy; Arginase; Arginine deiminase; Arginine decarboxylase	RECOMBINANT HUMAN ARGINASE; CELL-CYCLE ARREST; ADI-PEG 20; HUMAN HEPATOCELLULAR-CARCINOMA; IN-VIVO PROLIFERATION; NITRIC-OXIDE SYNTHASE; LACTIC-ACID BACTERIA; ARGININOSUCCINATE SYNTHETASE; TUMOR-CELLS; INHIBITS PROLIFERATION	Cancer is the second leading cause of death globally. Chemotherapy and radiation therapy and other medications are employed to treat various types of cancer. However, each treatment has its own set of side effects, owing to its low specificity. As a result, there is an urgent need for newer therapeutics that do not disrupt healthy cells' normal functioning. Depriving nutrient or non/semi-essential amino acids to which cancerous cells are auxotrophic remains one such promising anticancer strategy. l-Arginine (Arg) is a semi-essential vital amino acid involved in versatile metabolic processes, signaling pathways, and cancer cell proliferation. Hence, the administration of Arg depriving enzymes (ADE) such as arginase, arginine decarboxylase (ADC), and arginine deiminase (ADI) could be effective in cancer therapy. The Arg auxotrophic cancerous cells like hepatocellular carcinoma, human colon cancer, leukemia, and breast cancer cells are sensitive to ADE treatment due to low expression of crucial enzymes argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), and ornithine transcarbamylase (OCT). These therapeutic enzyme treatments induce cell death through inducing autophagy, apoptosis, generation of oxidative species, i.e., oxidative stress, and arresting the progression and expansion of cancerous cells at certain cell cycle checkpoints. The enzymes are undergoing clinical trials and could be successfully exploited as potential anticancer agents in the future.	[Kumari, Neha; Bansal, Saurabh] Jaypee Univ Informat Technol Waknaghat, Dept Biotechnol & Bioinformat, Solan 173234, Himachal Prades, India		Bansal, S (corresponding author), Jaypee Univ Informat Technol Waknaghat, Dept Biotechnol & Bioinformat, Solan 173234, Himachal Prades, India.	saurab.bansal02@gmail.com	Bansal, Saurabh/S-9094-2016	Bansal, Saurabh/0000-0002-0574-4063	Jaypee University of Information Technology Waknaghat, Solan, Himachal Pradesh, India	The authors acknowledge the Jaypee University of Information Technology Waknaghat, Solan, Himachal Pradesh, India, for providing infrastructure and financial support for carrying out the present work.	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J	De Angelis, ML; Francescangeli, F; La Torre, F; Zeuner, A				De Angelis, Maria Laura; Francescangeli, Federica; La Torre, Filippo; Zeuner, Ann			Stem Cell Plasticity and Dormancy in the Development of Cancer Therapy Resistance	FRONTIERS IN ONCOLOGY			English	Review						cancer stem cells; chemoresistance; dormancy; quiescence; plasticity; drug resistance; target therapies	DISSEMINATED TUMOR-CELLS; BREAST-CANCER; COLON-CANCER; TARGETED THERAPY; OXIDATIVE-PHOSPHORYLATION; EARLY DISSEMINATION; DRUG-RESISTANCE; OVARIAN-CANCER; METASTASIS; INHIBITION	Cancer treatment with either standard chemotherapy or targeted agents often results in the emergence of drug-refractory cell populations, ultimately leading to therapy failure. The biological features of drug resistant cells are largely overlapping with those of cancer stem cells and include heterogeneity, plasticity, self-renewal ability, and tumor-initiating capacity. Moreover, drug resistance is usually characterized by a suppression of proliferation that can manifest as quiescence, dormancy, senescence, or proliferative slowdown. Alterations in key cellular pathways such as autophagy, unfolded protein response or redox signaling, as well as metabolic adaptations also contribute to the establishment of drug resistance, thus representing attractive therapeutic targets. Moreover, a complex interplay of drug resistant cells with the micro/macroenvironment and with the immune system plays a key role in dictating and maintaining the resistant phenotype. Recent studies have challenged traditional views of cancer drug resistance providing innovative perspectives, establishing new connections between drug resistant cells and their environment and indicating unexpected therapeutic strategies. In this review we discuss recent advancements in understanding the mechanisms underlying drug resistance and we report novel targeting agents able to overcome the drug resistant status, with particular focus on strategies directed against dormant cells. Research on drug resistant cancer cells will take us one step forward toward the development of novel treatment approaches iand the improvement of relapse-free survival in solid and hematological cancer patients.	[De Angelis, Maria Laura; Francescangeli, Federica; Zeuner, Ann] Ist Super Sanita, Dept Oncol & Mol Med, Rome, Italy; [La Torre, Filippo] Sapienza Univ Rome, Policlin Umberto I, Dept Surg Sci, Rome, Italy		Zeuner, A (corresponding author), Ist Super Sanita, Dept Oncol & Mol Med, Rome, Italy.	ann.zeuner@iss.it	La Torre, Filippo/AAI-7284-2020; Francescangeli, Federica/K-6500-2016; De Angelis, Maria Laura/Y-4004-2019; Zeuner, Ann/K-8607-2016; Zeuner, Ann/A-8529-2010	La Torre, Filippo/0000-0002-0787-8794; Francescangeli, Federica/0000-0002-1086-5265; De Angelis, Maria Laura/0000-0003-4220-8822; Zeuner, Ann/0000-0002-8295-3715	ERA-NET TRANSCAN grant [TRS-2015-00000096]; Italian Association for Cancer Research (AIRC) Investigator GrantFondazione AIRC per la ricerca sul cancro [20744]; Awards Sapienza University of Rome grant [C26H15ZKWL]	This work was supported by an ERA-NET TRANSCAN grant TRS-2015-00000096 to AZ, by Italian Association for Cancer Research (AIRC) Investigator Grant 20744 to AZ, and by Awards Sapienza University of Rome grant C26H15ZKWL to FL.	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Oncol.	JUL 10	2019	9								626	10.3389/fonc.2019.00626			14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	IH8AE	WOS:000474725600004	31355143	Green Published, gold	Y	N	2022-04-25	
J	Scherr, AL; Jassowicz, A; Pato, A; Elssner, C; Ismail, L; Schmitt, N; Hoffmeister, P; Neukirch, L; Gdynia, G; Goeppert, B; Schulze-Bergkamen, H; Jager, D; Kohler, BC				Scherr, Anna-Lena; Jassowicz, Adam; Pato, Anna; Elssner, Christin; Ismail, Lars; Schmitt, Nathalie; Hoffmeister, Paula; Neukirch, Lasse; Gdynia, Georg; Goeppert, Benjamin; Schulze-Bergkamen, Henning; Jaeger, Dirk; Koehler, Bruno Christian			Knockdown of Atg7 Induces Nuclear-LC3 Dependent Apoptosis and Augments Chemotherapy in Colorectal Cancer Cells	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						Atg7; LC3; autophagy; apoptosis; colorectal cancer	CHAIN EXPRESSION; AUTOPHAGY; INHIBITION; PROTEINS; DISEASE; RESISTANCE; INITIATION; DEATH	Autophagy is a catabolic process that enables cells to degrade obsolete content and refuel energy depots. In colorectal cancer (CRC) autophagy has been shown to promote tumorigenesis through energy delivery in the condition of uncontrolled proliferation. With this study, we aimed at evaluating whether autophagy sustains CRC cell viability and if it impacts therapy resistance. Initially, a colorectal cancer tissue micro array, containing mucosa (n = 10), adenoma (n = 18) and adenocarcinoma (n = 49) spots, was stained for expression of essential autophagy proteins LC3b, Atg7, p62 and Beclin-1. Subsequently, central autophagy proteins were downregulated in CRC cells using siRNA technology. Viability assays, flow cytometry and immunoblotting were performed and three-dimensional cell culture was utilized to study autophagy in a tissue mimicking environment. In our study we found an upregulation of Atg7 in CRC. Furthermore, we identified Atg7 as crucial factor within the autophagy network for CRC cell viability. Its disruption induced cell death via triggering apoptosis and in combination with conventional chemotherapy it exerted synergistic effects in inducing CRC cell death. Cell death was strictly dependent on nuclear LC3b, since simultaneous knockdown of Atg7 and LC3b completely restored viability. This study unravels a novel cell death preventing function of Atg7 in interaction with LC3b, thereby unmasking a promising therapeutic target in CRC.	[Scherr, Anna-Lena; Jassowicz, Adam; Pato, Anna; Elssner, Christin; Ismail, Lars; Schmitt, Nathalie; Hoffmeister, Paula; Jaeger, Dirk; Koehler, Bruno Christian] Univ Hosp Heidelberg, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany; [Neukirch, Lasse] Natl Ctr Tumor Dis, Clin Cooperat Unit Appl Tumor Immun, D-69120 Heidelberg, Germany; [Neukirch, Lasse] German Canc Res Ctr, D-69120 Heidelberg, Germany; [Gdynia, Georg; Goeppert, Benjamin] Univ Hosp Heidelberg, Inst Pathol, D-69120 Heidelberg, Germany; [Schulze-Bergkamen, Henning] Marien Hosp, Dept Internal Med 2, D-4648 Wesel, Germany		Kohler, BC (corresponding author), Univ Hosp Heidelberg, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany.	anna-lena.scherr@nct-heidelberg.de; adam@jassowicz.com; patoannaterezia@gmail.com; Christin.Elssner@gmx.de; lars.ismail1986@googlemail.com; nathalie.schmitt@nct-heidelberg.de; paula.hoffmeister@googlemail.com; lasse.neukirch@nct-heidelberg.de; Georg.Gdynia@med.uni-heidelberg.de; Benjamin.Goeppert@med.uni-heidelberg.de; Henning.Schulze-Bergkamen@prohomine.de; dirk.jaeger@nct-heidelberg.de; bruno.koehler@nct-heidelberg.de	Goeppert, Benjamin/AAC-2303-2022	Pato, Anna/0000-0003-1238-3662; Neukirch, Lasse/0000-0002-2055-4743	German Research Foundation (DFG)German Research Foundation (DFG) [KO5205/1-1]; German Cancer Aid (DKH)Deutsche Krebshilfe [70113593]; Brigitte and Dr. KonstanzeWegener foundation; Medical Faculty of the University Heidelberg	This study was supported by a stipend of the Medical Faculty of the University Heidelberg to ALS (Rahel-Goitein-Strauss Program) and by research grants of the Brigitte and Dr. KonstanzeWegener foundation, the German Research Foundation (DFG, grant No. KO5205/1-1) and the German Cancer Aid (DKH, grant No. 70113593) to BCK.	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J. Mol. Sci.	FEB	2020	21	3							1099	10.3390/ijms21031099			15	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	KY4PQ	WOS:000522551607026	32046105	gold, Green Published			2022-04-25	
J	Caicedo-Lopez, LH; Cuellar-Nunez, ML; Luzardo-Ocampo, I; Campos-Vega, R; Loarca-Pina, G				Caicedo-Lopez, Laura H.; Cuellar-Nunez, M. Liceth; Luzardo-Ocampo, Ivan; Campos-Vega, Rocio; Loarca-Pina, Guadalupe			Colonic metabolites from digested Moringa oleifera leaves induced HT-29 cell death via apoptosis, necrosis, and autophagy	INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION			English	Article						Moringa oleifera; apoptosis; autophagy; colorectal cancer; colonic metabolites; short-chain fatty acids		Colorectal cancer is an important concern in modern society. Risk factors such as the diet indicate the need to find healthy food products displaying additional health benefits. This study aimed to characterise and evaluate the impact of the colonic metabolites from the fermented non-digestible fraction of Moringa oleifera (MO) leaves (FNFM) on cell death mechanisms from HT-29 cells. MO leaves were digested in vitro, and the 12 h-colonic extract was obtained. FNFM mainly contained morin and chlorogenic acids (41.97 and 25.33 mu g/g sample). Butyric acid was ranked as the most important metabolite of FNFM. The FNFM exerted antiproliferative effect against HT-29 colorectal cancer cells (half lethal concentration, LC50: 5.9 mL/100 mL). Compared to untreated control, LC50 increased H2O2 production (149.43%); induced apoptosis (119.02%), autophagy (75.60%), and necrosis (87.72%). These results suggested that digested MO colonic metabolites exert antiproliferative effect against HT-29 cells, providing additional health benefits associated with MO consumption.	[Caicedo-Lopez, Laura H.; Luzardo-Ocampo, Ivan; Campos-Vega, Rocio; Loarca-Pina, Guadalupe] Univ Autonoma Queretaro, Sch Chem, Res & Grad Program Food Sci, Queretaro, Mexico; [Caicedo-Lopez, Laura H.] Univ Autonoma Queretaro, Sch Engn, Biosyst Engn Grp, Queretaro, Mexico; [Cuellar-Nunez, M. Liceth] Univ Autonoma Queretaro, Fac Med, Queretaro, Mexico		Loarca-Pina, G (corresponding author), Univ Autonoma Queretaro, Sch Chem, Res & Grad Program Food Sci, Queretaro, Mexico.	loarca@uaq.mx	Luzardo-Ocampo, Ivan/R-4350-2019; Campos-Vega, Rocio/L-3151-2016	Luzardo-Ocampo, Ivan/0000-0002-8033-3520; CAICEDO LOPEZ, LAURA HELENA/0000-0001-5184-0112; Campos-Vega, Rocio/0000-0003-4054-1250; Loarca-Pina, Guadalupe/0000-0002-8416-9617	Consejo Nacional de Ciencia y Tecnologia (CONACyT-Mexico)Consejo Nacional de Ciencia y Tecnologia (CONACyT) [582098, 384201, 278375]; Universidad Autonoma de Queretaro [231214]	This work was supported by the Consejo Nacional de Ciencia y Tecnologia (CONACyT-Mexico) under Grant [grant number: 582098, 384201, and 278375]; Universidad Autonoma de Queretaro under Grant [grant number 231214].	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J. Food Sci. Nutr.	MAY 19	2021	72	4					485	498		10.1080/09637486.2020.1849039		NOV 2020	14	Food Science & Technology; Nutrition & Dietetics	Science Citation Index Expanded (SCI-EXPANDED)	Food Science & Technology; Nutrition & Dietetics	SB4IT	WOS:000597406800001	33302731				2022-04-25	
J	Min, H; Xu, M; Chen, ZR; Zhou, JD; Huang, M; Zheng, K; Zou, XP				Min, Han; Xu, Min; Chen, Zhi-rong; Zhou, Jun-dong; Huang, Min; Zheng, Kai; Zou, Xiao-ping			Bortezomib induces protective autophagy through AMP-activated protein kinase activation in cultured pancreatic and colorectal cancer cells	CANCER CHEMOTHERAPY AND PHARMACOLOGY			English	Article						Bortezomib; Autophagy; AMPK; Apoptosis-resistance and chemo-sensitization	SIGNALING PATHWAY; STEM-CELLS; ALK KINASE; NEUROBLASTOMA; DEATH; MUTATIONS; RECEPTOR; ENERGY; GROWTH; PHOSPHORYLATION	Bortezomib, a selective and potent inhibitor of the proteasome, has demonstrated broad anti-tumor activities in many malignancies. In the current study, we aimed to understand the potential resistance factor of bortezomib in cultured pancreatic and colorectal cancer cells. We observed that bortezomib-induced protective autophagy in cultured PANC-1 pancreatic cancer cells and HT-29 colorectal cancer cells. Inhibition of autophagy by 3-methyladenine (3-MA) and chloroquine enhanced bortezomib-induced apoptosis and cytotoxicity in both PANC-1 and HT-29 cells. Activation of AMP-activated protein kinase (AMPK) was required for bortezomib-induced autophagy induction in PANC-1 and HT-29 cells, and AMPK inhibition by its inhibitor compound C (CC) or RNAi-depletion suppressed bortezomib-induced autophagy, while dramatically enhancing cancer cell apoptosis/cytotoxicity. Meanwhile, significant AMPK activation and autophagy induction were observed after bortezomib stimulation in primary cultured pancreatic cancer cells derived from a patient's tumor tissue. Both CC and 3-MA facilitated bortezomib-induced cytotoxicity in primary cultured pancreatic cancer cells. In conclusion, our data here suggest that bortezomib induces protective autophagy in pancreatic and colorectal cancer cells through activating AMPK-Ulk1 signalings. AMPK or autophagy inhibitors could be developed as an adjunct or chemo-sensitizer for bortezomib.	[Min, Han; Zou, Xiao-ping] Nanjing Med Univ, Dept Gastroenterol, Drum Tower Clin Med Coll, Nanjing 210008, Peoples R China; [Min, Han; Chen, Zhi-rong] Nanjing Med Univ, Affiliated Suzhou Hosp, Dept Gastroenterol, Suzhou 215001, Peoples R China; [Xu, Min] Wuxi Peoples Hosp, Dept GI Med, Wuxi 214000, Jiangsu, Peoples R China; [Zhou, Jun-dong; Huang, Min; Zheng, Kai] Nanjing Med Univ, Suzhou Hosp, Tumor Lab, Suzhou 215001, Peoples R China		Zou, XP (corresponding author), Nanjing Med Univ, Dept Gastroenterol, Drum Tower Clin Med Coll, Zhongshan Rd 321, Nanjing 210008, Peoples R China.	minhanmd1981@163.com; szchenzhirong@163.com; zouxiaoping795@hotmail.com			National Natural Science FoundationNational Natural Science Foundation of China (NSFC)	This research was supported by grants from the National Natural Science Foundation (to Jun-dong Zhou).	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Pharmacol.	JUL	2014	74	1					167	176		10.1007/s00280-014-2451-7			10	Oncology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	AK9PT	WOS:000338759700016	24842158				2022-04-25	
J	Tirodkar, TS; Lu, P; Bai, AP; Scheffel, MJ; Gencer, S; Garrett-Mayer, E; Bielawska, A; Ogretmen, B; Voelkel-Johnson, C				Tirodkar, Tejas S.; Lu, Ping; Bai, Aiping; Scheffel, Matthew J.; Gencer, Salih; Garrett-Mayer, Elizabeth; Bielawska, Alicja; Ogretmen, Besim; Voelkel-Johnson, Christina			Expression of Ceramide Synthase 6 Transcriptionally Activates Acid Ceramidase in a c-Jun N-terminal Kinase (JNK)-dependent Manner	JOURNAL OF BIOLOGICAL CHEMISTRY			English	Article							COLON-CANCER CELLS; SPHINGOLIPID METABOLISM; INDUCED APOPTOSIS; CARCINOMA-CELLS; TUMOR-CELLS; INDUCTION; STRESS; AUTOPHAGY; LIVER; SUPPRESSION	A family of six ceramide synthases with distinct but overlapping substrate specificities is responsible for generation of ceramides with acyl chains ranging from similar to 14-26 carbons. Ceramide synthase 6 (CerS6) preferentially generates C-14- and C-16-ceramides, and we have previously shown that down-regulation of this enzyme decreases apoptotic susceptibility. In this study, we further evaluated how increased CerS6 expression impacts sphingolipid composition and metabolism. Overexpression of CerS6 in HT29 colon cancer cells resulted in increased apoptotic susceptibility and preferential generation of C-16-ceramide, which occurred at the expense of very long chain, saturated ceramides. These changes were also reflected in sphingomyelin composition. HT-CerS6 cells had increased intracellular levels of sphingosine, which is generated by ceramidases upon hydrolysis of ceramide. qRT-PCR analysis revealed that only expression of acid ceramidase (ASAH1) was increased. The increase in acid ceramidase was confirmed by expression and activity analyses. Pharmacological inhibition of JNK (SP600125) or curcumin reduced transcriptional up-regulation of acid ceramidase. Using an acid ceramidase promoter driven luciferase reporter plasmid, we demonstrated that CerS1 has no effect on transcriptional activation of acid ceramidase and that CerS2 slightly but significantly decreased the luciferase signal. Similar to CerS6, overexpression of CerS3-5 resulted in an similar to 2-fold increase in luciferase reporter gene activity. Exogenous ceramide failed to induce reporter activity, while a CerS inhibitor and a catalytically inactive mutant of CerS6 failed to reduce it. Taken together, these results suggest that increased expression of CerS6 can mediate transcriptional activation of acid ceramidase in a JNK-dependent manner that is independent of CerS6 activity.	[Tirodkar, Tejas S.; Lu, Ping; Scheffel, Matthew J.; Voelkel-Johnson, Christina] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA; [Bai, Aiping; Gencer, Salih; Bielawska, Alicja; Ogretmen, Besim] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA; [Garrett-Mayer, Elizabeth] Med Univ S Carolina, Dept Publ Hlth, Charleston, SC 29425 USA; [Gencer, Salih] Dept Mol Biol & Genet, TR-34662 Istanbul, Turkey		Voelkel-Johnson, C (corresponding author), Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave, Charleston, SC 29425 USA.	johnsocv@musc.edu	Regan, Clinton/E-6250-2012; Gencer, Salih/AAL-5502-2020; Gencer, Salih/B-6436-2012	Garrett-Mayer, Elizabeth/0000-0003-4709-0333	MUSC; Lipidomics and Flow Cytometry Shared Resources, Hollings Cancer Center, MUSC [P30 CA138313]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 CA154778];  [CA88032];  [CA173687];  [DE016572]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA173687, P30CA138313, P01CA154778] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [R01DE016572] Funding Source: NIH RePORTER	This project was supported by MUSC intramural funds (to C. V. J.) and in part by the Lipidomics and Flow Cytometry Shared Resources, Hollings Cancer Center, MUSC (P30 CA138313).; Supported by CA88032, CA173687, and DE016572.; Supported by National Institutes of Health Grant P01 CA154778.	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J	Liu, WM; Huang, P; Kar, N; Burgett, M; Muller-Greven, G; Nowacki, AS; Distelhorst, CW; Lathia, JD; Rich, JN; Kappes, JC; Gladson, CL				Liu, Wei Michael; Huang, Ping; Kar, Niladri; Burgett, Monica; Muller-Greven, Gaelle; Nowacki, Amy S.; Distelhorst, Clark W.; Lathia, Justin D.; Rich, Jeremy N.; Kappes, John C.; Gladson, Candece L.			Lyn Facilitates Glioblastoma Cell Survival under Conditions of Nutrient Deprivation by Promoting Autophagy	PLOS ONE			English	Article							SRC FAMILY KINASES; CHRONIC LYMPHOCYTIC-LEUKEMIA; COLON-CARCINOMA CELLS; MYELOGENOUS LEUKEMIA; TYROSINE KINASE; MONITORING AUTOPHAGY; PROSTATE-CANCER; RESISTANT CELLS; TUMOR-GROWTH; DNA-DAMAGE	Members of the Src family kinases (SFK) can modulate diverse cellular processes, including division, death and survival, but their role in autophagy has been minimally explored. Here, we investigated the roles of Lyn, a SFK, in promoting the survival of human glioblastoma tumor (GBM) cells in vitro and in vivo using lentiviral vector-mediated expression of constitutively-active Lyn (CA-Lyn) or dominant-negative Lyn (DN-Lyn). Expression of either CA-Lyn or DN-Lyn had no effect on the survival of U87 GBM cells grown under nutrient-rich conditions. In contrast, under nutrient-deprived conditions (absence of supplementation with L-glutamine, which is essential for growth of GBM cells, and FBS) CA-Lyn expression enhanced survival and promoted autophagy as well as inhibiting cell death and promoting proliferation. Expression of DN-Lyn promoted cell death. In the nutrient-deprived GBM cells, CA-Lyn expression enhanced AMPK activity and reduced the levels of pS6 kinase whereas DN-Lyn enhanced the levels of pS6 kinase. Similar results were obtained in vitro using another cultured GBM cell line and primary glioma stem cells. On propagation of the transduced GBM cells in the brains of nude mice, the CA-Lyn xenografts formed larger tumors than control cells and autophagosomes were detectable in the tumor cells. The DN-Lyn xenografts formed smaller tumors and contained more apoptotic cells. Our findings suggest that on nutrient deprivation in vitro Lyn acts to enhance the survival of GBM cells by promoting autophagy and proliferation as well as inhibiting cell death, and Lyn promotes the same effects in vivo in xenograft tumors. As the levels of Lyn protein or its activity are elevated in several cancers these findings may be of broad relevance to cancer biology.	[Liu, Wei Michael; Huang, Ping; Kar, Niladri; Burgett, Monica; Muller-Greven, Gaelle; Gladson, Candece L.] Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44106 USA; [Nowacki, Amy S.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA; [Lathia, Justin D.; Rich, Jeremy N.] Cleveland Clin, Lerner Res Inst, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44106 USA; [Burgett, Monica; Muller-Greven, Gaelle] Kent State Univ, Sch Biomed Sci, Kent, OH 44242 USA; [Distelhorst, Clark W.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA; [Kappes, John C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA		Gladson, CL (corresponding author), Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44106 USA.	gladsoc@ccf.org	Rich, Jeremy/AAM-1445-2021		NIH NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA043703, CA109748, CA127620, CA152883]; University of Alabama at Birmingham (UAB) Center for AIDS Research Virology and Sequencing Cores [P30-AI-27767]; Genetically Defined Microbe and Expression Core of the UAB Mucosal HIV and Immunobiology Center [R24 DK-64400]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA152883, R01CA127620, R01CA175120, R01CA085804, R01CA109748, P30CA043703] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [P30AI027767] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R24DK064400] Funding Source: NIH RePORTER	This work was supported by NIH NCI grants CA043703 (CWD), CA109748, CA127620 and CA152883(CLG), the University of Alabama at Birmingham (UAB) Center for AIDS Research Virology and Sequencing Cores (P30-AI-27767) and the Genetically Defined Microbe and Expression Core of the UAB Mucosal HIV and Immunobiology Center (R24 DK-64400) (JCK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Shi, Y; Xu, SF; Ngoi, NYL; Hui, YJ; Ye, Z				Shi, Yin; Xu, Shengfeng; Ngoi, Natalie Y. L.; Hui, Yuanjian; Ye, Zu			Rag GTPases suppress PRL-3 degradation and predict poor clinical diagnosis of cancer patients with low PRL-3 mRNA expression	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						Rag GTPases; PRL-3; Protein stability	MTORC1	Ras-related GTP binding (Rag) GTPases are required to activate mechanistic target of rapamycin complex 1 (mTORC1), which plays a central role in cell growth and metabolism and is considered as one of the most important oncogenic pathways. Therefore, Rag GTPases have been speculated to play a pro-cancer role via mTOR induction. However, aside from stimulation of mTOR signaling, firm links connecting Rag GTPase activity and their downstream effectors with cancer progression, remain largely unreported. In this study, we reported a novel link between RagB/C and a known oncoprotein phosphatase of regenerating liver-3 (PRL-3) by screening 22 pairs of tumors and their adjacent normal tissues from gastric, liver and lung cancers, and validating our findings in cancer cell lines with ectopic RagB/C expression. RagB/C was found to enhance PRL-3 stability by modulating two major cellular protein degradation pathways: lysosomal-autophagy and ubiquitin-proteasome system (UPS). Functionally, we identified the correlation between RagB/C expression with poor clinical outcomes in breast or colon cancer patients who also showed low PRL-3 mRNA expression from data retrieved from TCGA datasets, highlighting the potential relevance of Rag GTPase and PRL-3 mRNA in combination as a prognostic clinical biomarker. (c) 2021 Published by Elsevier Inc.	[Shi, Yin] Zhejiang Univ, Inst Immunol, Sch Med, Hangzhou, Peoples R China; [Shi, Yin; Ye, Zu] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore, Singapore; [Xu, Shengfeng] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA; [Ngoi, Natalie Y. L.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Invest Canc Therapeut, Houston, TX 77030 USA; [Ngoi, Natalie Y. L.] Natl Univ Canc Inst, Dept Hematol Oncol, Singapore, Singapore; [Hui, Yuanjian] Hubei Univ Med, Taihe Hosp, Dept Gen Surg, Shiyan, Hubei, Peoples R China; [Ye, Zu] ASTAR, Inst Mol & Cell Biol, Singapore, Singapore; [Ye, Zu] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA		Shi, Y (corresponding author), Zhejiang Univ, Inst Immunol, Sch Med, Hangzhou, Peoples R China.; Ye, Z (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.	yinshi@zju.edu.cn; zye4@mdanderson.org		Xu, Shengfeng/0000-0002-5774-7549	National Natural Sci-ence Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31801161]	This work was supported by grants from National Natural Sci-ence Foundation of China (No. 31801161) to Y.S.	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J	Dai, RC; Liu, MF; Nabil, WNN; Xi, ZC; Xu, HX				Dai, Rongchen; Liu, Mengfan; Nabil, Wan Najbah Nik; Xi, Zhichao; Xu, Hongxi			Mycomedicine: A Unique Class of Natural Products with Potent Anti-tumour Bioactivities	MOLECULES			English	Review						mycomedicine; medicinal fungi; anti-cancer; polysaccharides; triterpenoids	CELL-CYCLE ARREST; GANODERMA-LUCIDUM POLYSACCHARIDE; HEPATOCELLULAR-CARCINOMA GROWTH; AGARICUS-BLAZEI MURILL; COLON-CANCER CELLS; GRIFOLA-FRONDOSA; IN-VITRO; ANTICANCER PROPERTIES; BIOLOGICAL-ACTIVITIES; MOLECULAR-MECHANISMS	Mycomedicine is a unique class of natural medicine that has been widely used in Asian countries for thousands of years. Modern mycomedicine consists of fruiting bodies, spores, or other tissues of medicinal fungi, as well as bioactive components extracted from them, including polysaccharides and, triterpenoids, etc. Since the discovery of the famous fungal extract, penicillin, by Alexander Fleming in the late 19th century, researchers have realised the significant antibiotic and other medicinal values of fungal extracts. As medicinal fungi and fungal metabolites can induce apoptosis or autophagy, enhance the immune response, and reduce metastatic potential, several types of mushrooms, such as Ganoderma lucidum and Grifola frondosa, have been extensively investigated, and anti-cancer drugs have been developed from their extracts. Although some studies have highlighted the anti-cancer properties of a single, specific mushroom, only limited reviews have summarised diverse medicinal fungi as mycomedicine. In this review, we not only list the structures and functions of pharmaceutically active components isolated from mycomedicine, but also summarise the mechanisms underlying the potent bioactivities of several representative mushrooms in the Kingdom Fungi against various types of tumour.	[Dai, Rongchen; Liu, Mengfan; Nabil, Wan Najbah Nik; Xi, Zhichao] Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China; [Nabil, Wan Najbah Nik] Minist Hlth, Pharmaceut Serv Program, Petaling Jaya 46200, Selangor, Malaysia; [Xu, Hongxi] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Shanghai 201203, Peoples R China		Xi, ZC (corresponding author), Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China.; Xu, HX (corresponding author), Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Shanghai 201203, Peoples R China.	ycy220823@gmail.com; mengfanliush@163.com; najbah@yahoo.com; xizhichao@shutcm.edu.cn; hxxu@shutcm.edu.cn	Dai, Rongchen/AAO-4747-2021; Xi, Zhichao/AAD-5842-2020; Liu, Mengfan/AAO-4758-2021; Rongchen, DAI/AAQ-8585-2021	Xi, Zhichao/0000-0001-7366-9045; Liu, Mengfan/0000-0002-5402-5102; Xu, Hongxi/0000-0001-6238-4511; Nik Nabil, Wan Najbah/0000-0001-6400-8691	National Natural Science Foundation ofChinaNational Natural Science Foundation of China (NSFC) [.81803571, 81973438]; NSFC-Joint Foundation of Yunnan Province [U1902213]; Key-Area Research and Development Program of Guangdong Province [2020B1111110003]	This researchwas funded by National Natural Science Foundation ofChina (GrantNo.81803571, 81973438); NSFC-Joint Foundation of Yunnan Province (Grant No. U1902213); Key-Area Research and Development Program of Guangdong Province (Grant No. 2020B1111110003).	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Chemistry	QP9JH	WOS:000624144700001	33669877	Green Published, gold			2022-04-25	
J	Wang, H; Wang, YA; Qian, L; Wang, X; Gu, HL; Dong, XQ; Huang, SQ; Jin, M; Ge, HL; Xu, CF; Zhang, YY				Wang, Hui; Wang, Yanan; Qian, Liu; Wang, Xue; Gu, Hailiang; Dong, Xiaoqiang; Huang, Shiqian; Jin, Min; Ge, Hailiang; Xu, Congfeng; Zhang, Yanyun			RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy	ONCOTARGET			English	Article						RNF216; BECN1; autophagy; colorectal cancer	BECLIN 1; DEGRADATION; TRIAD3A; GROWTH; SWITCH; CELLS	Originally identified as an E3 ligase regulating toll-like receptor (TLR) signaling, ring finger protein 216 (RNF216) also plays an essential role in autophagy, which is fundamental to cellular homeostasis. Autophagy dysfunction leads to an array of pathological events, including tumor formation. In this study, we found that RNF216 was upregulated in human colorectal cancer (CRC) tissues and cell lines, and was associated with progression of CRC. RNF216 promoted CRC cell proliferation and migration in vitro and in vivo, largely by enhancing proteasomal degradation of BECN1, a key autophagy regulator and tumor suppressor. RNF216 restricted CRC cell autophagy through BECN1 inhibition under nutritional starvation conditions. RNF216 knockdown increased the autophagy, limiting CRC cell proliferation and migration. Moreover, BECN1 knockdown or autophagy inhibition restored proliferation and migration of RNF216-knockdown CRC cells. Collectively, our results suggested that RNF216 promoted CRC cell proliferation and migration by negatively regulating BECN1-dependent autophagy. This makes RNF216 as a potential biomarker and novel therapeutic target for inhibiting CRC development and progression.	[Wang, Hui; Wang, Yanan; Qian, Liu; Wang, Xue; Huang, Shiqian; Jin, Min; Ge, Hailiang; Xu, Congfeng; Zhang, Yanyun] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Immunol, Inst Med Sci,SJTUSM, Shanghai, Peoples R China; [Wang, Hui; Wang, Yanan; Qian, Liu; Wang, Xue; Huang, Shiqian; Jin, Min; Ge, Hailiang; Xu, Congfeng; Zhang, Yanyun] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China; [Wang, Hui; Wang, Yanan; Qian, Liu; Wang, Xue; Huang, Shiqian; Jin, Min; Ge, Hailiang; Xu, Congfeng; Zhang, Yanyun] SJTUSM, Shanghai, Peoples R China; [Gu, Hailiang; Dong, Xiaoqiang] Soochow Univ, Affiliated Hosp 1, Dept Gen Surg, Suzhou, Peoples R China		Ge, HL; Xu, CF; Zhang, YY (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Immunol, Inst Med Sci,SJTUSM, Shanghai, Peoples R China.; Ge, HL; Xu, CF; Zhang, YY (corresponding author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China.; Ge, HL; Xu, CF; Zhang, YY (corresponding author), SJTUSM, Shanghai, Peoples R China.	ghl@shsmu.edu.cn; cxu@shsmu.edu.cn; yyzhang@sibs.ac.cn	Xu, Congfeng/E-4806-2013	Xu, Congfeng/0000-0002-8009-4865	Ministry of Science and Technology of ChinaMinistry of Science and Technology, China [2015CB943303, 2014CB943303]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81502607, 81502506, 31570905, 31300708, 81471217]; Program of Science and Technology Commission of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [15JC1402900, 13ZR1423200, 14ZR1446300]	This study was supported by the Ministry of Science and Technology of China (2015CB943303, 2014CB943303), National Natural Science Foundation of China (81502607, 81502506, 31570905, 31300708 and 81471217), the Program of Science and Technology Commission of Shanghai Municipality (15JC1402900, 13ZR1423200 and 14ZR1446300).	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J	Bahreyni-Toossi, MT; Dolat, E; Khanbabaei, H; Zafari, N; Azimian, H				Bahreyni-Toossi, Mohammad-Taghi; Dolat, Elham; Khanbabaei, Hashem; Zafari, Navid; Azimian, Hosein			microRNAs: Potential glioblastoma radiosensitizer by targeting radiation-related molecular pathways	MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS			English	Review						Radiosensitivity; Radiation therapy; Ionizing radiation; Glioblastoma; Cancer; microRNA	GLIOMA STEM-CELLS; BREAST-CANCER CELLS; ROS PRODUCTION; TUMOR-GROWTH; ENHANCES RADIOSENSITIVITY; AUTOPHAGY INHIBITION; COLON-CANCER; U87MG CELLS; DNA-REPAIR; EXPRESSION	Glioblastoma (GBM) is the most lethal type of primary brain tumor. Currently, even with optimal and multimodal cancer therapies, the survival rate of GBM patients remains poor. One reason for inadequate response of GBM tumors to radiotherapy is radioresistance (RR). Thus, there is a critical need for new insights about GBM treatment to increase the chance of treatment. microRNAs (miRNAs) are important regulatory molecules that can effectively control GBM radiosensitivity (RS) by affecting radiation-related signal transduction pathways such as apoptosis, proliferation, DNA repair and cell cycle regulation. miRNAs provide new clinical perspectives for developing effective GBM treatments. A growing body of literature has demonstrated that GBM RS can be modified by modulating the expression of miRNAs such as miR-7, miR-10b, miR-124, miR-128, miR-320, miR-21, miR-203, and miR-153. This paper highlights the miRNAs and the underlying molecular mechanisms that are involved in the RS of GBM. Besides highlighting the role of miRNAs in different signaling pathways, we explain the mechanisms that affect RS of GBM for modulating radiation response at the clinical level.	[Bahreyni-Toossi, Mohammad-Taghi; Azimian, Hosein] Mashhad Univ Med Sci, Med Phys Res Ctr, Buali Sq,Ferdousi Sq,POB 9196773117, Mashhad, Razavi Khorasan, Iran; [Dolat, Elham; Zafari, Navid] Mashhad Univ Med Sci, Fac Med, Dept Med Phys, Mashhad, Razavi Khorasan, Iran; [Khanbabaei, Hashem] Ahvaz Jundishapur Univ Med Sci, Fac Med, Med Phys Dept, Ahvaz, Iran		Azimian, H (corresponding author), Mashhad Univ Med Sci, Med Phys Res Ctr, Buali Sq,Ferdousi Sq,POB 9196773117, Mashhad, Razavi Khorasan, Iran.; Zafari, N (corresponding author), Mashhad Univ Med Sci, Fac Med, Dept Med Phys, Mashhad, Razavi Khorasan, Iran.	ZafariGN941@mums.ac.ir; AzimianH@mums.ac.ir	Azimian, Hosein/N-4866-2018	Azimian, Hosein/0000-0003-2951-8228; Dolat, Elham/0000-0002-3207-0850	Iran National Science Foundation (INSF)Iran National Science Foundation (INSF)	The authors would like to thank the Iran National Science Foundation (INSF) for financial support of this work.	Abraki S. 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Res.-Fundam. Mol. Mech. Mutagen.	NOV	2019	816								111679	10.1016/j.mrfmmm.2019.111679			9	Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology	JS7YO	WOS:000500519700008	31715522				2022-04-25	
J	Koustas, E; Sarantis, P; Kyriakopoulou, G; Papavassiliou, AG; Karamouzis, MV				Koustas, Evangelos; Sarantis, Panagiotis; Kyriakopoulou, Georgia; Papavassiliou, Athanasios G.; Karamouzis, Michalis, V			The Interplay of Autophagy and Tumor Microenvironment in Colorectal Cancer-Ways of Enhancing Immunotherapy Action	CANCERS			English	Review						Autophagy; colorectal cancer; immunotherapy; tumor stroma; tumor microenvironment	MISMATCH-REPAIR DEFICIENCY; REGULATORY T-CELLS; MICROSATELLITE INSTABILITY; SUPPRESSOR-CELLS; PROTEIN BECLIN-1; PD-L2 EXPRESSION; STROMAL CELLS; MYELOID CELLS; NEUTROPHILS; ACTIVATION	Autophagy as a primary homeostatic and catabolic process is responsible for the degradation and recycling of proteins and cellular components. The mechanism of autophagy has a crucial role in several cellular functions and its dysregulation is associated with tumorigenesis, tumor-stroma interactions, and resistance to cancer therapy. A growing body of evidence suggests that autophagy is also a key regulator of the tumor microenvironment and cellular immune response in different types of cancer, including colorectal cancer (CRC). Furthermore, autophagy is responsible for initiating the immune response especially when it precedes cell death. However, the role of autophagy in CRC and the tumor microenvironment remains controversial. In this review, we identify the role of autophagy in tumor microenvironment regulation and the specific mechanism by which autophagy is implicated in immune responses during CRC tumorigenesis and the context of anticancer therapy.	[Koustas, Evangelos; Sarantis, Panagiotis; Kyriakopoulou, Georgia; Papavassiliou, Athanasios G.; Karamouzis, Michalis, V] Natl & Kapodistrian Univ Athens, Med Sch, Dept Biol Chem, Mol Oncol Unit, Athens 11527, Greece; [Karamouzis, Michalis, V] Natl & Kapodistrian Univ Athens, Med Sch, Laiko Gen Hosp, Dept Internal Med 1, Athens 11527, Greece		Karamouzis, MV (corresponding author), Natl & Kapodistrian Univ Athens, Med Sch, Dept Biol Chem, Mol Oncol Unit, Athens 11527, Greece.; Karamouzis, MV (corresponding author), Natl & Kapodistrian Univ Athens, Med Sch, Laiko Gen Hosp, Dept Internal Med 1, Athens 11527, Greece.	vang.koustas@gmail.com; psarantis@bioacademy.gr; gpkyriakopoulou@yahoo.com; papavas@med.uoa.gr; mkaramouz@med.uoa.gr	Sarantis, Panagiotis/AAF-4774-2021; Koustas, Evangelos/ABE-9336-2020; Karamouzis, Michalis/AAD-2860-2020	Sarantis, Panagiotis/0000-0001-5848-7905; Papavassiliou, Athanasios/0000-0001-5803-4527; Karamouzis, Michalis/0000-0003-1369-8201			Amaravadi RK, 2012, AUTOPHAGY, V8, P1383, DOI 10.4161/auto.20958; 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J	Gullulu, O; Hehlgans, S; Rodel, C; Fokas, E; Rodel, F				Guelluelue, Oemer; Hehlgans, Stephanie; Roedel, Claus; Fokas, Emmanouil; Roedel, Franz			Tumor Suppressor Protein p53 and Inhibitor of Apoptosis Proteins in Colorectal Cancer-A Promising Signaling Network for Therapeutic Interventions	CANCERS			English	Review						cIAP1; 2; colorectal carcinoma; inhibitor of apoptosis protein family; Survivin; TP53; XIAP; BRUCE; LIVIN		Simple Summary Tumor suppressor 53 (p53) is a multifunctional protein that regulates cell cycle, DNA repair, apoptosis and metabolic pathways. In colorectal cancer (CRC), mutations of the gene occur in 60% of patients and are associated with a more aggressive tumor phenotype and resistance to anti-cancer therapy. In addition, inhibitor of apoptosis (IAP) proteins are distinguished biomarkers overexpressed in CRC that impact on a diverse set of signaling pathways associated with the regulation of apoptosis/autophagy, cell migration, cell cycle and DNA damage response. As these mechanisms are further firmly controlled by p53, a transcriptional and post-translational regulation of IAPs by p53 is expected to occur in cancer cells. Here, we aim to review the molecular regulatory mechanisms between IAPs and p53 and discuss the therapeutic potential of targeting their interrelationship by multimodal treatment options. Despite recent advances in the treatment of colorectal cancer (CRC), patient's individual response and clinical follow-up vary considerably with tumor intrinsic factors to contribute to an enhanced malignancy and therapy resistance. Among these markers, upregulation of members of the inhibitor of apoptosis protein (IAP) family effects on tumorigenesis and radiation- and chemo-resistance by multiple pathways, covering a hampered induction of apoptosis/autophagy, regulation of cell cycle progression and DNA damage response. These mechanisms are tightly controlled by the tumor suppressor p53 and thus transcriptional and post-translational regulation of IAPs by p53 is expected to occur in malignant cells. By this, cellular IAP1/2, X-linked IAP, Survivin, BRUCE and LIVIN expression/activity, as well as their intracellular localization is controlled by p53 in a direct or indirect manner via modulating a multitude of mechanisms. These cover, among others, transcriptional repression and the signal transducer and activator of transcription (STAT)3 pathway. In addition, p53 mutations contribute to deregulated IAP expression and resistance to therapy. This review aims at highlighting the mechanistic and clinical importance of IAP regulation by p53 in CRC and describing potential therapeutic strategies based on this interrelationship.	[Guelluelue, Oemer; Hehlgans, Stephanie; Roedel, Claus; Fokas, Emmanouil; Roedel, Franz] Univ Hosp Frankfurt, Dept Radiotherapy & Oncol, Theodor Stern Kai 7, D-60590 Frankfurt, Germany; [Roedel, Claus; Fokas, Emmanouil; Roedel, Franz] Goethe Univ Frankfurt, Frankfurt Canc Inst FCI, Theodor Stern Kai 7, D-60590 Frankfurt, Germany; [Roedel, Claus; Fokas, Emmanouil; Roedel, Franz] German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany; [Roedel, Claus; Fokas, Emmanouil; Roedel, Franz] German Canc Consortium DKTK, Partner Site, D-60590 Frankfurt, Germany		Rodel, F (corresponding author), Univ Hosp Frankfurt, Dept Radiotherapy & Oncol, Theodor Stern Kai 7, D-60590 Frankfurt, Germany.; Rodel, F (corresponding author), Goethe Univ Frankfurt, Frankfurt Canc Inst FCI, Theodor Stern Kai 7, D-60590 Frankfurt, Germany.; Rodel, F (corresponding author), German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.; Rodel, F (corresponding author), German Canc Consortium DKTK, Partner Site, D-60590 Frankfurt, Germany.	oemer.guelluelue@kgu.de; stephanie.hehlgans@kgu.de; claus.roedel@kgu.de; emmanouil.fokas@kgu.de; franz.roedel@kgu.de		Rodel, Franz/0000-0001-6057-1022; Gullulu, Omer/0000-0003-0218-7721	German Research Foundation (DFG) (Graduate school GRK 1657)German Research Foundation (DFG); German Federal Ministry of Education and Research (BMBF)Federal Ministry of Education & Research (BMBF) [GREWISalpha: 02NUK050D]	This research was funded by the German Research Foundation (DFG) (Graduate school GRK 1657, projects 2B) and the German Federal Ministry of Education and Research (BMBF), grant number GREWISalpha: 02NUK050D.	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J	Wu, J; Wu, JJ; Yang, LJ; Wei, LX; Zou, DJ				Wu, Jie; Wu, Jun-jie; Yang, Lin-jun; Wei, Li-xin; Zou, Da-jin			Rosiglitazone protects against palmitate-induced pancreatic beta-cell death by activation of autophagy via 5 '-AMP-activated protein kinase modulation	ENDOCRINE			English	Article						Rosiglitazone; Autophagy; Palmitate; AMPK	ENDOPLASMIC-RETICULUM STRESS; COLON-CANCER CELL; MOLECULAR-MECHANISMS; INSULIN-RESISTANCE; INDUCED APOPTOSIS; RECEPTOR-GAMMA; MASS; LIPOTOXICITY; INHIBITION; TOXICITY	Promoting beta-cell survival is crucial for the prevention of beta-cell failure in diabetes. Thiazolidinediones, a widely used drug to improve insulin sensitivity in clinical practice, is found to have a protective effect on islet beta-cell. To date, the mechanism underlying the protective role of thiazolidinedione on beta-cell survival remain largely unknown. Activation of autophagy was detected by transmission electron microscopy, western blot, and GFP-LC3 transfection. Cell viability was examined by WST-8. Cell apoptosis was demonstrated by DAPI and Annexin V/PI staining. Colony formation assay was used to detect long-term cell viability. We demonstrated that rosiglitazone-treated beta-cells were more resistant to palmitate-induced apoptosis. The conversion of LC3-I to LC3-II and accumulated autophagosomes were found to be upregulated in rosiglitazone-treated cells. Inhibition of autophagy augmented palmitate-induced apoptosis with rosiglitazone treatment, suggesting that autophagy plays an important role in the survival function of rosiglitazone on beta-cells. Furthermore, we showed that rosiglitazone could induce AMP-activated protein kinase (AMPK) phosphorylation and reduce p70S6 kinase phosphorylation. Inhibition of AMPK impaired autophagy activation and enhanced palmitate-induced apoptosis during rosiglitazone treatment. These findings reveal that rosiglitazone-induced autophagy contributes to its protective function on beta-cells during palmitate treatment.	[Wu, Jie; Zou, Da-jin] Second Mil Med Univ, Chang Hai Hosp, Dept Endocrinol, Shanghai 200438, Peoples R China; [Wu, Jie] Tongji Univ, Tong Ji Hosp, Dept Endocrinol, Shanghai, Peoples R China; [Wu, Jie] Fudan Univ, Sch Life Sci, Key Lab Contemporary Anthropol, Natl Minist Educ, Shanghai 200433, Peoples R China; [Yang, Lin-jun] Second Mil Med Univ, Chang Hai Hosp, Dept Oncol, Shanghai 200438, Peoples R China; [Wei, Li-xin] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Tumor Immunol, Shanghai 200438, Peoples R China; [Wei, Li-xin] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Gene Therapy Ctr, Shanghai 200438, Peoples R China		Zou, DJ (corresponding author), Second Mil Med Univ, Chang Hai Hosp, Dept Endocrinol, 168 Changhai Rd, Shanghai 200438, Peoples R China.	jielin1080@gmail.com; zwjd22@medmail.com.cn			Special Funds for National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81070619]; Commission of Science and Technology of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [08411967100]	This project was supported by the Special Funds for National Natural Science Foundation of China (Grant No. 81070619), the Commission of Science and Technology of Shanghai Municipality (No. 08411967100).	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J	Yoshioka, A; Miyata, H; Doki, Y; Yamasaki, M; Sohma, I; Gotoh, K; Takiguchi, S; Fujiwara, Y; Uchiyama, Y; Monden, M				Yoshioka, Akiko; Miyata, Hiroshi; Doki, Yuichiro; Yamasaki, Makoto; Sohma, Itsuro; Gotoh, Kunihito; Takiguchi, Shuji; Fujiwara, Yoshiyuki; Uchiyama, Yasuo; Monden, Morito			LC3, an autophagosome marker, is highly expressed in gastrointestinal cancers	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						light chain 3; autophagy; cancer development; gastrointestinal cancer; esophageal cancer	MONITORING AUTOPHAGY; RAT HEPATOCYTES; CELL-SURVIVAL; DEATH; YEAST; TUMORIGENESIS; INHIBITION; DISSECTION; RADIATION; PATHWAYS	Autophagy is a bulk protein and organelle degradation process essential for cell maintenance and viability. Microtubule-associated protein I light chain 3 (LC3), the mammalian homologue of yeast Atg8, is involved in autophagosome formation during autophagy. The aim of this study was to investigate LC3 expression in gastrointestinal cancers to elucidate the role of autophagy in human cancer development. We evaluated LC3 expression by immunohistochemistry in 163 gastrointestinal cancers including 106 esophageal, 38 gastric and 19 colorectal cancers. Seventy precancerous intraepithelial neoplasias were found in esophageal cancer specimens. LC3 expression was compared with Ki-67 staining and expression of carbonic anhydrase (CA) IX, a hypoxic marker. LC3 was expressed in the cytoplasm of cancer cells, but not in noncancerous epithelial cells. A high expression of LC3 was observed in 53% of esophageal, 58% of gastric and 63% of colorectal cancers. LC3 immunoreactive score gradually increased during early esophageal carcinogenesis in low- and high-grade intraepithelial neoplasia and T1 carcinoma, while it did not change in later cancer progression (T2-T4 carcinomas). In early esophageal carcinogenesis, LC3 expression correlated with Ki-67 labeling index (p=0.0001), but showed no significant association with CAIX expression. In esophageal cancers, LC3 expression did not correlate with various clinicopathological factors, including survival. LC3 is upregulated in various gastrointestinal cancers and partly associated with Ki-67 index. Our results suggest that LC3 expression is advantageous to cancer development especially in early-phase carcinogenesis.	[Yoshioka, Akiko; Miyata, Hiroshi; Doki, Yuichiro; Yamasaki, Makoto; Sohma, Itsuro; Gotoh, Kunihito; Takiguchi, Shuji; Fujiwara, Yoshiyuki; Monden, Morito] Osaka Univ, Dept Surg Gastroenterol, Grad Sch Med, Suita, Osaka 5650871, Japan; [Gotoh, Kunihito; Uchiyama, Yasuo] Osaka Univ, Dept Cell Biol & Neurosci, Grad Sch Med, Suita, Osaka 5650871, Japan		Miyata, H (corresponding author), Osaka Univ, Dept Surg Gastroenterol, Grad Sch Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.	hmiyata@surg2.med.osaka-u.ac.jp					Aita VM, 1999, GENOMICS, V59, P59, DOI 10.1006/geno.1999.5851; Alva AS, 2004, CELL DEATH DIFFER, V11, P1046, DOI 10.1038/sj.cdd.4401445; Amaravadi RK, 2007, J CLIN INVEST, V117, P326, DOI 10.1172/JCI28833; ASHFORD TP, 1962, J CELL BIOL, V12, P198, DOI 10.1083/jcb.12.1.198; Beasley NJP, 2001, CANCER RES, V61, P5262; Blommaart EFC, 1997, HISTOCHEM J, V29, P365, DOI 10.1023/A:1026486801018; Cuervo AM, 2004, TRENDS CELL BIOL, V14, P70, DOI 10.1016/j.tcb.2003.12.002; Degenhardt K, 2006, CANCER CELL, V10, P51, DOI 10.1016/j.ccr.2006.06.001; Edinger AL, 2003, CANCER CELL, V4, P422, DOI 10.1016/S1535-6108(03)00306-4; Elmore SP, 2001, FASEB J, V15, P2286, DOI 10.1096/fj.01-0206fje; Hemelaar J, 2003, J BIOL CHEM, V278, P51841, DOI 10.1074/jbc.M308762200; Inbal B, 2002, J CELL BIOL, V157, P455, DOI 10.1083/jcb.200109094; Jin SK, 2007, AUTOPHAGY, V3, P28, DOI 10.4161/auto.3269; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; Kato K, 2002, ONCOGENE, V21, P6082, DOI 10.1038/sj.onc.1205737; Klionsky DJ, 2007, AUTOPHAGY, V3, P181, DOI 10.4161/auto.3678; Klionsky DJ, 2000, SCIENCE, V290, P1717, DOI 10.1126/science.290.5497.1717; Klionsky DJ, 2003, DEV CELL, V5, P539, DOI 10.1016/S1534-5807(03)00296-X; Kondo Y, 2005, NAT REV CANCER, V5, P726, DOI 10.1038/nrc1692; Levine B, 2005, CELL, V120, P159, DOI 10.1016/j.cell.2005.01.005; Levine B, 2007, NATURE, V446, P745, DOI 10.1038/446745a; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Lu ZH, 2005, ARCH HISTOL CYTOL, V68, P71, DOI 10.1679/aohc.68.71; Martinet W, 2006, J HISTOCHEM CYTOCHEM, V54, P85, DOI 10.1369/jhc.5A6743.2005; Meijer AJ, 2004, INT J BIOCHEM CELL B, V36, P2445, DOI 10.1016/j.biocel.2004.02.002; Meijer AJ, 2004, BIOCHEM BIOPH RES CO, V313, P397, DOI 10.1016/j.bbrc.2003.07.012; Miyata H, 2000, CLIN CANCER RES, V6, P4859; Mizushima N, 2001, J CELL BIOL, V152, P657, DOI 10.1083/jcb.152.4.657; Mizushima N, 2004, INT J BIOCHEM CELL B, V36, P2491, DOI 10.1016/j.biocel.2004.02.005; Mizushima N, 2004, MOL BIOL CELL, V15, P1101, DOI 10.1091/mbc.E03-09-0704; Munafo DB, 2001, J CELL SCI, V114, P3619; Ogier-Denis E, 2003, BBA-REV CANCER, V1603, P113, DOI 10.1016/S0304-419X(03)00004-0; Ohsumi Y, 2001, NAT REV MOL CELL BIO, V2, P211, DOI 10.1038/35056522; Paglin S, 2001, CANCER RES, V61, P439; Petiot A, 2000, J BIOL CHEM, V275, P992, DOI 10.1074/jbc.275.2.992; Pouyssegur J, 2006, NATURE, V441, P437, DOI 10.1038/nature04871; Qu XP, 2007, CELL, V128, P931, DOI 10.1016/j.cell.2006.12.044; Rusten TE, 2004, DEV CELL, V7, P179, DOI 10.1016/j.devcel.2004.07.005; Sobin L H, 2002, TNM CLASSIFICATION M, V6th; Tanida I, 2004, INT J BIOCHEM CELL B, V36, P2503, DOI 10.1016/j.biocel.2004.05.009; TSUKADA M, 1993, FEBS LETT, V333, P169, DOI 10.1016/0014-5793(93)80398-E; Uchiyama Y, 2001, ARCH HISTOL CYTOL, V64, P233, DOI 10.1679/aohc.64.233; Yamamoto H, 2003, GASTROENTEROLOGY, V125, P556, DOI 10.1016/S0016-5085(03)00904-1	43	163	167	0	17	PROFESSOR D A SPANDIDOS	ATHENS	1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE	1019-6439			INT J ONCOL	Int. J. Oncol.	SEP	2008	33	3					461	468		10.3892/ijo_00000028			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	352TE	WOS:000259519500005	18695874	Bronze			2022-04-25	
J	Kreis, NN; Louwen, F; Yuan, J				Kreis, Nina-Naomi; Louwen, Frank; Yuan, Juping			The Multifaceted p21 (Cip1/Waf1/CDKN1A) in Cell Differentiation, Migration and Cancer Therapy	CANCERS			English	Review						p21; CDKN1A; differentiation; migration; metastasis; anti-cancer therapy	DEPENDENT KINASE INHIBITOR; NUCLEOTIDE EXCISION-REPAIR; EPITHELIAL-MESENCHYMAL TRANSITION; CYTOPLASMIC P21(WAF1/CIP1) EXPRESSION; SMALL-MOLECULE INHIBITORS; HUMAN COLON-CANCER; BREAST-CANCER; CDK INHIBITORS; DNA-REPLICATION; GENE-EXPRESSION	Loss of cell cycle control is characteristic of tumorigenesis. The protein p21 is the founding member of cyclin-dependent kinase inhibitors and an important versatile cell cycle protein. p21 is transcriptionally controlled by p53 and p53-independent pathways. Its expression is increased in response to various intra- and extracellular stimuli to arrest the cell cycle ensuring genomic stability. Apart from its roles in cell cycle regulation including mitosis, p21 is involved in differentiation, cell migration, cytoskeletal dynamics, apoptosis, transcription, DNA repair, reprogramming of induced pluripotent stem cells, autophagy and the onset of senescence. p21 acts either as a tumor suppressor or as an oncogene depending largely on the cellular context, its subcellular localization and posttranslational modifications. In the present review, we briefly mention the general functions of p21 and summarize its roles in differentiation, migration and invasion in detail. Finally, regarding its dual role as tumor suppressor and oncogene, we highlight the potential, difficulties and risks of using p21 as a biomarker as well as a therapeutic target.	[Kreis, Nina-Naomi; Louwen, Frank; Yuan, Juping] Goethe Univ Frankfurt, Univ Hosp, Dept Gynecol & Obstet, Theodor Stern Kai 7, D-60590 Frankfurt, Germany		Kreis, NN (corresponding author), Goethe Univ Frankfurt, Univ Hosp, Dept Gynecol & Obstet, Theodor Stern Kai 7, D-60590 Frankfurt, Germany.	Nina-Naomi.Kreis@kgu.de	Kreis, Nina-Naomi/AAF-5407-2019	Kreis, Nina-Naomi/0000-0003-4304-0160; Yuan, Juping/0000-0003-0694-0565	Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)German Research Foundation (DFG) [390921723]	This research was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-project number 390921723.	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J	Vidhyapriya, P; Divya, D; Bala, M; Sakthivel, N				Vidhyapriya, P.; Divya, D.; Bala, Manimaran; Sakthivel, N.			Photoactivated [Mn(CO)(3)Br(mu-bpcpd)](2) induces apoptosis in cancer cells via intrinsic pathway	JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY			English	Article						Carbon Monoxide Releasing Molecule; Apoptosis; Targeted Therapy; Photoactivation	MONOXIDE-RELEASING MOLECULE; CARBON-MONOXIDE; CORM-3 RU(CO)(3)CL(GLYCINATE); TRICARBONYL COMPLEXES; MITOCHONDRIAL PATHWAY; CYTOTOXICITY; MANGANESE(I); RESPIRATION; GENERATION; AUTOPHAGY	Carbon monoxide releasing molecules (CORMs) are organometallic/organic compounds that release carbon monoxide (CO) spontaneously or upon activation. PhotoCORMs are capable of releasing CO on light based activation. This group of molecules is used in photodynamic therapy due to their ability to release CO in a controlled manner. In the present investigation, the release of CO from [Mn(CO)(3)Br(mu-bpcpd)](2) (MnCORM) upon irradiation at lambda(max) 365 nm was assessed spectrophotometrically using myoglobin assay and confirmed by liquid FT-IR spectroscopic analysis. Further, the cytotoxic potential of MnCORM on normal cells (HEK 293) and cancer cell lines such as lung (A549), cervical (HeLa), breast (MDA MB-231) and colon (HCT-15) was evaluated. The IC50 values of MnCORM were found to be 21.37 +/- 1.72, 24.12 +/- 1.03, 21.89 +/- 0.59 and 13.69 +/- 0.91 mu M on cervical (HeLa), lung (A549), colon (HCT-15) and breast (MDA MB-231) cancer cells respectively. An inquest into the nature of cell death was confirmed based on the nuclear and cytological examinations, flow cytometric analyses and protein expression studies. The AO/EB dual staining and cytological evaluation of the treated cells revealed that the cell death might be due to apoptosis. The flow cytometric analysis of propidium iodide (PI) stained cells showed a significant amount of sub-G1 hypodiploid cells due to MnCORM treatment. The MnCORM-induced apoptosis was mediated through the generation of reactive oxygen species (ROS), specifically superoxide radicals leading to loss of mitochondrial membrane potential. The intrinsic pathway of apoptosis was elucidated based on the expression studies of pro-apoptotic and apoptotic proteins such as bcl-2, bax, cyt c, cleaved caspase-3, cleaved caspase-9 and cleaved PARP. Due to its innate potential to release CO upon photo activation and its ability to induce apoptosis via intrinsic pathway, the MnCORM molecule could be exploited for controlled release and photodynamic cancer therapy.	[Vidhyapriya, P.; Sakthivel, N.] Pondicherry Univ, Dept Biotechnol, Pondicherry 605014, India; [Divya, D.; Bala, Manimaran] Pondicherry Univ, Dept Chem, Pondicherry 605014, India		Sakthivel, N (corresponding author), Pondicherry Univ, Sch Life Sci, Dept Biotechnol, Pondicherry 605014, India.	manimaran.che@pondiuni.edu.in; puns2005@gmail.com		D, Divya/0000-0002-8127-2678	DBTDepartment of Biotechnology (DBT) India; CSIRCouncil of Scientific & Industrial Research (CSIR) - India	The authors thank DBT for providing Junior Research Fellowship to P. Vidhyapriya and are also thankful to CSIR for financial support. The authors acknowledge the facilities provided through Central Instrument Facility (CIF) of Pondicherry University and DST-FIST and UGC-SAP Programmes coordinated by Prof. N. Sakthivel.	ARPANSA N. S. 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Photochem. Photobiol. B-Biol.	NOV	2018	188						28	41		10.1016/j.jphotobiol.2018.08.021			14	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	GZ2TN	WOS:000449241400005	30195977				2022-04-25	
J	Wang, YZ; Lina, L; Xu, L; Yang, Z; Qian, Z; Zhou, J; Suoni, L				Wang, Yuzhen; Lina, Li; Xu, Li; Yang, Zhai; Qian, Zhang; Zhou, Jing; Suoni, Li			Arctigenin enhances the sensitivity of cisplatin resistant colorectal cancer cell by activating autophagy	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						Arctigenin; Cisplatin; Colorectal cancer; Autophagy; SW480; SW620	MULTIDRUG-RESISTANCE; PREVENTION	Arctigenin is the active content of arctium lappa that present anti-cancer abilities in various carcinomas. However, its role and underlying mechanism in drug-resistant colorectal cancer cells has not been addressed. The present study used SW480 and SW620 to established cisplatin-resistant colorectal cancer cell lines, and explored the impact of arctigenin on these cells. Arctigenin at 100 mu M significantly inhibited cell proliferation of cisplatin treated R-SW480 and R-SW620 cells as compared with cells treated with cisplatin alone. Arctigenin elevates cell apoptosis, up-regulated pro-apoptotic protein cleaved-caspase-3 and caspase-9 expression level in cisplatin treated R-SW480 and R-SW620 cells. Additionally, arctigenin triggered autophagy and promoted LC3-II and p65 expression, while inhibited LC3-lexpression. Arctigenin impeded the IC50 of not only cisplatin but also oxaliplatin, doxorubicin and Paclitaxel of R-SW480 and R-SW620 cells. More importantly, the mRNA expression of multi drug resistance 1 (MDR1) and protein expression of pgp were significantly inhibited by arctigenin administration. Taken together, arctigenin has the potential in sensitize colorectal cancer cells by activating autophagy, which induced cell apoptosis and inhibited cell growth. Our study revealed that arctigenin has the potential for colorectal cancer treatment and may be useful in adjuvant chemotherapy. (C) 2019 Elsevier Inc. All rights reserved.	[Wang, Yuzhen; Lina, Li; Xu, Li; Yang, Zhai; Qian, Zhang; Zhou, Jing; Suoni, Li] Shaanxi Prov Tumor Hosp, Dept Internal Med, 309 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China		Wang, YZ (corresponding author), Shaanxi Prov Tumor Hosp, Dept Internal Med, 309 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China.	wangyzhos@163.com					Bhat P, 2018, BIOCHEM PHARMACOL, V147, P170, DOI 10.1016/j.bcp.2017.11.021; Brenner H, 2014, LANCET, V383, P1490, DOI 10.1016/S0140-6736(13)61649-9; Carlotto J, 2016, INT J BIOL MACROMOL, V91, P954, DOI 10.1016/j.ijbiomac.2016.06.033; Cocker HA, 2001, CLIN CANCER RES, V7, P3193; Deng ZW, 2019, MED SCI MONITOR, V25, P2386, DOI 10.12659/MSM.915866; Du Y, 2017, DRUG DES DEV THER, V11, P1255, DOI 10.2147/DDDT.S134529; El-Kott AF, 2015, CURR THER RES CLIN E, V77, P73, DOI 10.1016/j.curtheres.2015.05.001; Feng Q, 2018, FRONT IMMUNOL, V9, DOI 10.3389/fimmu.2018.01881; Han YH, 2017, AM J CHINESE MED, V45, P1309, DOI 10.1142/S0192415X17500720; He YH, 2018, BIOMED PHARMACOTHER, V108, P403, DOI 10.1016/j.biopha.2018.08.158; Huang SQ, 2019, EVID-BASED COMPL ALT, V2019, DOI 10.1155/2019/8423037; Huang YJ, 2019, BIOMOLECULES, V9, DOI 10.3390/biom9080306; Koulenti D., 2019, MICROORGANISMS, V7; Kuipers EJ, 2015, NAT REV DIS PRIMERS, V1, DOI 10.1038/nrdp.2015.65; Li QC, 2016, J BUON, V21, P87; Maxwell T, 2018, INT J ONCOL, V52, P1339, DOI 10.3892/ijo.2018.4271; McQuade RM, 2017, CURR MED CHEM, V24, P1537, DOI 10.2174/0929867324666170111152436; Morse MA, 2020, ONCOLOGIST, V25, P33, DOI 10.1634/theoncologist.2019-0176; Ravanan P, 2017, LIFE SCI, V188, P53, DOI 10.1016/j.lfs.2017.08.029; Sharma AK, 2008, J CONTROL RELEASE, V131, P220, DOI 10.1016/j.jconrel.2008.07.031; Sonowal H, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-03284-w; Wang EJ, 2019, MOLECULES, V24, DOI 10.3390/molecules24162968; Wisselink DD, 2019, CRIT REV ONCOL HEMAT, V142, P119, DOI 10.1016/j.critrevonc.2019.06.014; Yadav SS, 2019, LIFE SCI, V220, P169, DOI 10.1016/j.lfs.2019.02.005; Yan JH, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-019-1355-0; Yao HX, 2019, EXP THER MED, V17, P4363, DOI 10.3892/etm.2019.7501; Yoon SB, 2019, J MICROBIOL BIOTECHN, V29, P571, DOI 10.4014/jmb.1901.01061; Zhang ZM, 2017, TUMOR BIOL, V39, DOI 10.1177/1010428317705575	28	16	17	0	17	ACADEMIC PRESS INC ELSEVIER SCIENCE	SAN DIEGO	525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA	0006-291X	1090-2104		BIOCHEM BIOPH RES CO	Biochem. Biophys. Res. Commun.	NOV 26	2019	520	1					20	26		10.1016/j.bbrc.2019.09.086			7	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	KB3OU	WOS:000506410000004	31564411				2022-04-25	
J	Lai, YY; Lim, DN; Tan, PH; Leung, TKC; Yip, GWC; Bay, BH				Lai, Yiyang; Lim, Daina; Tan, Puay-Hoon; Leung, Thomas King-Chor; Yip, George Wai-Cheong; Bay, Boon-Huat			Silencing the Metallothionein-2A Gene Induces Entosis in Adherent MCF-7 Breast Cancer Cells	ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY			English	Article						metallothionein-2A; breast cancer; entosis; cell-in-cell; electron microscopy	CANNIBALISM; EXPRESSION; CARCINOMA; CYTOLOGY; DEATH	The presence of a live cell cohabiting within another cell has fascinated scientists for many decades. Far from being a spurious event, many have attempted to uncover the molecular mechanism underlying this phenomenon. In this study, we observed anchorage-dependent MCF-7 cells internalizing neighboring epithelial cells (entosis) after siRNA-mediated silencing of the Metallothionein-2A (MT-2A) gene. MTs belong to a family of low-molecular weight proteins, which bind metal ions endogenously and its over-expression has been reported in a variety of cancers that include breast, prostate, and colon. We provide microscopic evidence at light and ultrastructural levels of the occurrence of entosis after altering MT expression in a subpopulation of MCF-7 breast cancer cells by silencing the MT-2A gene. Our results demonstrate that adheren junctions may play important roles in the formation of cell-in-cell cytostructure after MT-2A. gene downregulation and the entotic process does not appear to involve genes associated with autophagy. Interiorized cells often underwent lysosomal degradation within the cytoplasmic body of the engulfing cell. It would appear that a subset of breast cancer cells could die via entosis after MT-2A gene silencing. Anat Rec, 293:1685-1691, 2010. (C) 2010 Wiley-Liss, Inc.	[Lai, Yiyang; Lim, Daina; Yip, George Wai-Cheong; Bay, Boon-Huat] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anat, Singapore 117597, Singapore; [Tan, Puay-Hoon] Singapore Gen Hosp, Dept Pathol, Singapore 169608, Singapore; [Leung, Thomas King-Chor] Natl Univ Singapore, Inst Mol & Cell Biol, GSK IMCB Grp, Singapore 117548, Singapore		Bay, BH (corresponding author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anat, 4 Med Dr,Blk MD 10, Singapore 117597, Singapore.	antbaybh@nus.edu.sg			Singapore National Medical Research CouncilNational Medical Research Council, Singapore [NMRC/1019/2005, NMRC/1081/2006]; National University of SingaporeNational University of Singapore	Grant sponsor: Singapore National Medical Research Council; Grant numbers: NMRC/1019/2005; NMRC/1081/2006.; The authors would like to thank Song-Lin Bay, Yajun Wu and Yee-Gek Chan for skilful technical assistance. Yiyang Lai is a recipient of a Research Scholarship from the National University of Singapore.	Abodief WT, 2006, CYTOPATHOLOGY, V17, P304, DOI 10.1111/j.1365-2303.2006.00326.x; BROUWER M, 1984, CANCER RES, V44, P2947; Cherian MG, 2003, MUTAT RES-FUND MOL M, V533, P201, DOI 10.1016/j.mrfmmm.2003.07.013; do Amaral JB, 2010, CELL BIOL INT, V34, P267, DOI 10.1042/CBI20090024; Fais S, 2007, CANCER LETT, V258, P155, DOI 10.1016/j.canlet.2007.09.014; HUMBLE JG, 1956, BRIT J HAEMATOL, V2, P283, DOI 10.1111/j.1365-2141.1956.tb06700.x; Ip WKE, 2009, IMMUNOL REV, V230, P9, DOI 10.1111/j.1600-065X.2009.00789.x; Jin RX, 2002, CARCINOGENESIS, V23, P81, DOI 10.1093/carcin/23.1.81; Kojima SI, 1998, ACTA CYTOL, V42, P1365, DOI 10.1159/000332169; Kroemer G, 2009, CELL DEATH DIFFER, V16, P3, DOI 10.1038/cdd.2008.150; Lewis WH, 1925, ANAT REC, V31, P43, DOI 10.1002/ar.1090310106; Lim D, 2009, CANCER LETT, V276, P109, DOI 10.1016/j.canlet.2008.10.038; Mididoddi S, 1996, TOXICOL LETT, V85, P17, DOI 10.1016/0378-4274(96)03632-6; Ng WK, 2003, ACTA CYTOL, V47, P56, DOI 10.1159/000326476; Overholtzer M, 2008, NAT REV MOL CELL BIO, V9, P796, DOI 10.1038/nrm2504; Overholtzer M, 2007, CELL, V131, P966, DOI 10.1016/j.cell.2007.10.040; Pedersen MO, 2009, PROG HISTOCHEM CYTO, V44, P29, DOI 10.1016/j.proghi.2008.10.001; Rozen S, 2000, Methods Mol Biol, V132, P365; Tai SK, 2003, AM J PATHOL, V163, P2009, DOI 10.1016/S0002-9440(10)63559-6; Tsolaki AG, 2009, ADV EXP MED BIOL, V653, P185; White E, 2007, CELL, V131, P840, DOI 10.1016/j.cell.2007.11.015; Wu YT, 2008, AUTOPHAGY, V4, P457, DOI 10.4161/auto.5662; Xia P, 2008, CELL RES, V18, P705, DOI 10.1038/cr.2008.64	23	19	19	0	14	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1932-8486	1932-8494		ANAT REC	Anat. Rec.	OCT	2010	293	10					1685	1691		10.1002/ar.21215			7	Anatomy & Morphology	Science Citation Index Expanded (SCI-EXPANDED)	Anatomy & Morphology	668LX	WOS:000283272600006	20652934				2022-04-25	
J	Xu, HY; Jiang, BH; Meng, L; Ren, TT; Zeng, Y; Wu, J; Qu, LK; Shou, CC				Xu, Huiyu; Jiang, Beihai; Meng, Lin; Ren, Tingting; Zeng, Yan; Wu, Jian; Qu, Like; Shou, Chengchao			N-alpha-Acetyltransferase 10 protein inhibits apoptosis through RelA/p65-regulated MCL1 expression	CARCINOGENESIS			English	Article							FACTOR-KAPPA-B; DOWN-REGULATION; POOR-PROGNOSIS; KB ACTIVATION; CANCER-CELLS; TARGET	N-alpha-Acetyltransferase 10 protein (Naa10p/ARD1), the catalytic subunit of N-acetyltransferase A, catalyzes both N-alpha-acetylation and epsilon-acetylation, as well as autoacetylation. Naa10p is involved in controlling cell proliferation, apoptosis, autophagy and neuronal development. Our group and others had reported prognostic value of Naa10p expression in various types of cancer. Despite the efforts to elucidate the biological function of Naa10p, it remains controversial regarding its roles in tumor development. Herein, we report that depletion of Naa10p inhibited the growth of xenograft tumors in nude mice. Microarray analysis identified MCL1 gene as one of targets downstream of Naa10p. Naa10p positively regulated MCL1 expression, as exogenous Naa10p promoted MCL1 expression, whereas Naa10p silencing decreased MCL1 expression. Ablation of Naa10p sensitized cancer cells to stimuli-induced apoptosis, and the anti-apoptotic function of Naa10p was, at least in part, mediated by MCL1. Mechanistically, we found a physical interaction between Naa10p and RelA/p65. Transcriptional activation of the MCL1 gene required the recruitment of Naa10p RelA/p65 complex to the p65-binding site of MCL1 promoter region. We also demonstrated a positive correlation between MCL1 and Naa10p messenger RNA levels in both colon cancer and lung cancer tissues. These results indicate that Naa10p inhibits apoptosis through Naa10p RelA/p65-dependent MCL1 transcriptional activation.	[Xu, Huiyu; Jiang, Beihai; Meng, Lin; Ren, Tingting; Zeng, Yan; Wu, Jian; Qu, Like; Shou, Chengchao] Peking Univ, Canc Hosp & Inst, Dept Biochem & Mol Biol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China		Shou, CC (corresponding author), Peking Univ, Canc Hosp & Inst, Dept Biochem & Mol Biol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China.	qulike@bjcancer.org; scc@bjcancer.org			National 973 Program of ChinaNational Basic Research Program of China [2009CB521805]; National 863 Program of ChinaNational High Technology Research and Development Program of China [2006AA02A402-B07]; National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81071658]	National 973 Program of China (2009CB521805), National 863 Program of China (2006AA02A402-B07) and National Nature Science Foundation of China (81071658).	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J	Alotaibi, M; Sharma, K; Saleh, T; Povirk, LF; Hendrickson, EA; Gewirtz, DA				Alotaibi, Moureq; Sharma, Khushboo; Saleh, Tareq; Povirk, Lawrence F.; Hendrickson, Eric A.; Gewirtz, David A.			Radiosensitization by PARP Inhibition in DNA Repair Proficient and Deficient Tumor Cells: Proliferative Recovery in Senescent Cells	RADIATION RESEARCH			English	Article							DOUBLE-STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; PROSTATE-CANCER RECURRENCE; DEPENDENT PROTEIN-KINASE; ACCELERATED SENESCENCE; LUNG-CANCER; CYTOTOXIC AUTOPHAGY; DAMAGE-RESPONSE; SINGLE-STRAND; HOMOLOGOUS RECOMBINATION	Radiotherapy continues to be a primary modality in the treatment of cancer. In addition to promoting apoptosis, radiation-induced DNA damage can promote autophagy and senescence, both of which can theoretically function to prolong tumor survival. In this work, we tested the hypothesis that autophagy and/or senescence could be permissive for DNA repair, thereby facilitating tumor cell recovery from radiation-induced growth arrest and/or cell death. In addition, studies were designed to elucidate the involvement of autophagy and senescence in radiosensitization by PARP inhibitors and the re-emergence of a proliferating tumor cell population. In the context of this work, the relationship between radiation-induced autophagy and senescence was also determined. Studies were performed using DNA repair-proficient HCT116 colon carcinoma cells and a repair-deficient ligase IV-/- isogenic cell line. Exposure to radiation promoted a parallel induction of autophagy and senescence that was strongly correlated with the extent of persistent H2AX phosphorylation in both cell lines, however, inhibition of autophagy failed to suppress senescence, indicating that the two responses were dissociable. Exposure to radiation resulted in a transient arrest in the HCT116 cells while arrest was prolonged in the ligase IV-/- cells, however, both cell lines ultimately recovered proliferative function, which may reflect maintenance of DNA repair capacity. The PARP inhibitors, olaparib and niraparib, increased the extent of persistent DNA damage induced by radiation exposure as well as the extent of both autophagy and senescence. Neither cell line underwent significant apoptosis by radiation exposure alone or in the presence of the PARP inhibitors. Inhibition of autophagy failed to attenuate radiosensitization, indicating that autophagy was not involved in the action of the PARP inhibitors. As with radiation alone, despite sensitization by PARP inhibition, proliferative recovery was evident within a period of 10-20 days. While inhibition of DNA repair via PARP inhibition may initially sensitize tumor cells to radiation via the promotion of senescence, this strategy does not appear to interfere with proliferative recovery, which could ultimately contribute to disease recurrence. (C) 2016 by Radiation Research Society	[Alotaibi, Moureq; Sharma, Khushboo; Saleh, Tareq; Povirk, Lawrence F.; Gewirtz, David A.] Virginia Commonwealth Univ, Sch Med, Dept Pharmacol & Toxicol, Med Coll Virginia Campus, Richmond, VA 23298 USA; [Gewirtz, David A.] Virginia Commonwealth Univ, Massey Canc Ctr, 401 Coll St, Richmond, VA 23298 USA; [Alotaibi, Moureq] King Saud Univ, Coll Pharm, Dept Pharmacol & Toxicol, Riyadh 11451, Saudi Arabia; [Hendrickson, Eric A.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA		Gewirtz, DA (corresponding author), Virginia Commonwealth Univ, Massey Canc Ctr, 401 Coll St, Richmond, VA 23298 USA.	david.gewirtz@vcuhealth.org	Saleh, Tareq/AGY-9225-2022	Saleh, Tareq/0000-0002-2878-1107	National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA40615, CA166264, CA154461, CA190492]; National Institutes of General Medical SciencesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [GM088351]; Office of the Assistant Secretary of Defense for Health Affairs through the Breast Cancer Research Program [W81XWH-14-1-0088]; Massey Center Support Grant [P30 CA016059]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA190492, R01CA040615, R01CA154461, P30CA016059, R01CA166264] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM088351] Funding Source: NIH RePORTER	This work was supported by the National Cancer Institute [grant nos. CA40615 (LFP), CA166264 ( LFP), CA154461 (EAH) and CA190492 (EAH)], the National Institutes of General Medical Sciences [grant no. GM088351 (EAH)] and the Office of the Assistant Secretary of Defense for Health Affairs through the Breast Cancer Research Program [grant no. W81XWH-14-1-0088 (DAG)], and Massey Center Support Grant P30 CA016059.	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Res.	MAR	2016	185	3					229	245		10.1667/RR14202.1			17	Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging	Science Citation Index Expanded (SCI-EXPANDED)	Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging	DN0KY	WOS:000376754000003	26934368	Green Accepted			2022-04-25	
J	Jiang, Q				Jiang, Qing			Natural forms of vitamin E and metabolitesregulation of cancer cell death and underlying mechanisms	IUBMB LIFE			English	Review						sphingolipids; cancer prevention; apoptosis; autophagy; ceramides; tocopherols; tocotrienols; long-chain carboxychromanol; inflammation; food; colon cancer; prostate cancer; breast cancer; biology; medicine	NF-KAPPA-B; E DELTA-TOCOTRIENOL; LONG-CHAIN CARBOXYCHROMANOLS; STEM-LIKE CELLS; GAMMA-TOCOPHEROL; PROSTATE-CANCER; INDUCED APOPTOSIS; ALPHA-TOCOPHEROL; INDUCE APOPTOSIS; MOUSE MODEL	The disappointing results from large clinical studies of -tocopherol (T), the major form of vitamin E in tissues, for prevention of chronic diseases including cancer have cast doubt on not only T but also other forms of vitamin E regarding their role in preventing carcinogenesis. However, basic research has shown that specific forms of vitamin E such as -tocopherol (T), -tocopherol (T), -tocotrienol (TE) and -tocotrienol (TE) can inhibit the growth and induce death of many types of cancer cells, and are capable of suppressing cancer development in preclinical cancer models. For these activities, these vitamin E forms are much stronger than T. Further, recent research revealed novel anti-inflammatory and anticancer effects of vitamin E metabolites including 13-carboxychromanols. This review focuses on anti-proliferation and induction of death in cancer cells by vitamin E forms and metabolites, and discuss mechanisms underlying these anticancer activities. The existing in vitro and in vivo evidence indicates that T, T, tocotrienols and 13-carboxychromanols have anti-cancer activities via modulating key signaling or mediators that regulate cell death and tumor progression, such as eicosanoids, NF-B, STAT3, PI3K, and sphingolipid metabolism. These results provide useful scientific rationales and mechanistic understanding for further translation of basic discoveries to the clinic with respect to potential use of these vitamin E forms and metabolites for cancer prevention and therapy. (c) 2018 IUBMB Life, 71(4):495-506, 2019	[Jiang, Qing] Purdue Univ, Dept Nutr Sci, 700 W State St,Stone Hall G1A, W Lafayette, IN 47907 USA		Jiang, Q (corresponding author), Purdue Univ, Dept Nutr Sci, 700 W State St,Stone Hall G1A, W Lafayette, IN 47907 USA.	qjiang@purdue.edu		Jiang, Qing/0000-0002-0579-8280	National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01ES023349];  [P30CA023168]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA023168] Funding Source: NIH RePORTER	The sole author is responsible for all aspects of the paper. This work was in part supported by a grant R01ES023349 (QJ) from National Institutes of Health and a pilot grant from Purdue University Center for Cancer Research, P30CA023168.	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Yap WN, 2010, PHARMACOLOGY, V85, P248, DOI 10.1159/000278205; Yap WN, 2008, BRIT J CANCER, V99, P1832, DOI 10.1038/sj.bjc.6604763; Ye CX, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0122712; Yu H, 2014, NAT REV CANCER, V14, P736, DOI 10.1038/nrc3818; Yu WP, 1999, NUTR CANCER, V33, P26, DOI 10.1080/01635589909514744; Yue SH, 2014, CELL METAB, V19, P393, DOI 10.1016/j.cmet.2014.01.019; Zhang JS, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0057779	120	27	28	0	12	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1521-6543	1521-6551		IUBMB LIFE	IUBMB Life	APR	2019	71	4			SI		495	506		10.1002/iub.1978			12	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	HP4TU	WOS:000461669800010	30548200	Bronze			2022-04-25	
J	Zhang, CR; Jiang, J; Wang, LQ; Zheng, LY; Xu, JK; Qi, XL; Huang, HY; Lu, JP; Li, KN; Wang, H				Zhang, Chunrui; Jiang, Jing; Wang, Liqiang; Zheng, Liyu; Xu, Jiankai; Qi, Xiaolin; Huang, Huiying; Lu, Jianping; Li, Kongning; Wang, Hong			Identification of Autophagy-Associated Biomarkers and Corresponding Regulatory Factors in the Progression of Colorectal Cancer	FRONTIERS IN GENETICS			English	Article						autophagy; colorectal cancer; regulatory network; RNA-binding proteins; biomarkers	CELL-DEATH; EXPRESSION; RESOURCE; GENES; SUSCEPTIBILITY; RECURRENCE; PROGNOSIS; SURVIVAL	Autophagy is a self-degradation process that maintains homeostasis against stress in cells. Autophagy dysfunction plays a central role in the development of tumors, such as colorectal cancer (CRC). In this study, autophagy-related differentially expressed genes, their downstream functions, and upstream regulatory factors including RNA-binding proteins (RBP) involved in programmed cell death in the CRC were investigated. Transcription factors (TFs) and miRNAs have been shown to mainly regulate autophagy genes. Interestingly, we found that some of the RBP in the CRC, such as DDX17, SETDB1, and POLR3A, play an important regulatory role in maintaining autophagy at a basal level during growth by acting as TFs that regulate autophagy. Promoter methylations showed negative regulations on differentially expressed autophagy gene (DEAG), while copy number variations revealed a positive role in them. A proportional hazards regression analysis indicated that using autophagy-related prognostic signature can divide patients into high-risk and low-risk groups. Autophagy associated FDA-approved drugs were studied by a prognostic network. This would contribute to the identifications of new potential molecular therapeutic targets for CRC.	[Zhang, Chunrui; Wang, Liqiang; Zheng, Liyu; Xu, Jiankai; Huang, Huiying; Lu, Jianping; Li, Kongning] Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Peoples R China; [Zhang, Chunrui] Chinese Acad Sci, Inst Genet & Dev Biol, Beijing, Peoples R China; [Jiang, Jing] Harbin Med Univ, Affiliated Hosp 2, Obstet & Gynecol Dept, Harbin, Peoples R China; [Qi, Xiaolin; Li, Kongning; Wang, Hong] Hainan Med Univ, Minist Educ, Key Lab Trop Translat Med, Haikou, Hainan, Peoples R China; [Qi, Xiaolin; Li, Kongning; Wang, Hong] Hainan Med Univ, Coll Biomed Informat & Engn, Haikou, Hainan, Peoples R China		Lu, JP; Li, KN (corresponding author), Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Peoples R China.; Li, KN; Wang, H (corresponding author), Hainan Med Univ, Minist Educ, Key Lab Trop Translat Med, Haikou, Hainan, Peoples R China.; Li, KN; Wang, H (corresponding author), Hainan Med Univ, Coll Biomed Informat & Engn, Haikou, Hainan, Peoples R China.	lujianping1992@163.com; likongning@hainmc.edu.cn; wanghong@hainmc.edu.cn	Li, Kongning/L-6188-2015	Li, Kongning/0000-0002-4928-6922; ZHANG, CHUNRUI/0000-0002-8170-5509	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31501075, 31301094, 31900493]; Natural Science Foundation of Heilongjiang ProvinceNatural Science Foundation of Heilongjiang Province [B201302]; Postdoctoral Foundation of Heilongjiang Province [LBH-Z18167]	This work was supported by the National Natural Science Foundation of China (31501075, 31301094, and 31900493), the Natural Science Foundation of Heilongjiang Province (B201302), and the Postdoctoral Foundation of Heilongjiang Province (LBH-Z18167).	Arntzen MO, 2013, J PROTEOME RES, V12, P2206, DOI 10.1021/pr4000703; Barretina J, 2012, NATURE, V483, P603, DOI 10.1038/nature11003; Boglev Y, 2013, PLOS GENET, V9, DOI 10.1371/journal.pgen.1003279; Catalina-Rodriguez O, 2012, ONCOTARGET, V3, P1220; Chatterji P, 2018, TRENDS MOL MED, V24, P490, DOI 10.1016/j.molmed.2018.03.008; Chen Y, 2014, GENET MOL RES, V13, P3228, DOI 10.4238/2014.April.25.8; Chin L, 2008, NATURE, V455, P1061, DOI 10.1038/nature07385; Chisanga D, 2016, NUCLEIC ACIDS RES, V44, pD969, DOI 10.1093/nar/gkv1097; Chou CH, 2018, NUCLEIC ACIDS RES, V46, pD296, DOI 10.1093/nar/gkx1067; Eaden J, 2003, ALIMENT PHARM THER, V18, P15, DOI 10.1046/j.1365-2036.18.s2.3.x; Garay-Lugo N, 2016, IMMUNOPHARM IMMUNOT, V38, P353, DOI 10.1080/08923973.2016.1208221; GEORGIADES Y, 1988, SCI TOTAL ENVIRON, V77, P215, DOI 10.1016/0048-9697(88)90057-5; Gerstberger S, 2014, NAT REV GENET, V15, P829, DOI 10.1038/nrg3813; Guo JQ, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0140745; Hao HB, 2017, MED MOL MORPHOL, V50, P76, DOI 10.1007/s00795-016-0150-7; Harrow J, 2012, GENOME RES, V22, P1760, DOI 10.1101/gr.135350.111; Hu Y, 2018, GENE CHROMOSOME CANC, V57, P140, DOI 10.1002/gcc.22512; Huang DW, 2009, NUCLEIC ACIDS RES, V37, P1, DOI 10.1093/nar/gkn923; Jiang L, 2017, METAB ENG, V43, P198, DOI 10.1016/j.ymben.2016.11.004; Katheder NS, 2017, NATURE, V541, P417, DOI 10.1038/nature20815; Kim HY, 2015, INTEST RES, V13, P233, DOI 10.5217/ir.2015.13.3.233; Kudinov AE, 2017, CLIN CANCER RES, V23, P2143, DOI 10.1158/1078-0432.CCR-16-2728; Lin G, 2014, BRIT J CANCER, V111, P375, DOI 10.1038/bjc.2014.281; Lossos IS, 2004, NEW ENGL J MED, V350, P1828, DOI 10.1056/NEJMoa032520; Mei Y, 2016, BIOCHEMISTRY-US, V55, P1945, DOI 10.1021/acs.biochem.5b01264; New J, 2019, MOL CARCINOGEN, V58, P1400, DOI 10.1002/mc.23023; Prasad TSK, 2009, NUCLEIC ACIDS RES, V37, pD767, DOI 10.1093/nar/gkn892; Rovito D, 2015, BBA-GEN SUBJECTS, V1850, P2185, DOI 10.1016/j.bbagen.2015.08.004; Roy S, 2010, SEMIN IMMUNOPATHOL, V32, P383, DOI 10.1007/s00281-010-0213-0; Smith JJ, 2010, GASTROENTEROLOGY, V138, P958, DOI 10.1053/j.gastro.2009.11.005; Tan YQ, 2016, MEDIAT INFLAMM, V2016, DOI 10.1155/2016/4867368; Thorburn A, 2014, MOL PHARMACOL, V85, P830, DOI 10.1124/mol.114.091850; Vlachos IS, 2015, NUCLEIC ACIDS RES, V43, pD153, DOI 10.1093/nar/gku1215; Wang H, 2016, ONCOTARGET, V7, P51174, DOI 10.18632/oncotarget.9433; Wang YF, 2015, INT J CLIN EXP MED, V8, P12661; Williams FP, 2019, BIOL CHEM, V400, P1443, DOI 10.1515/hsz-2019-0158; Xiao FF, 2009, NUCLEIC ACIDS RES, V37, pD105, DOI 10.1093/nar/gkn851; Yang MP, 2015, ONCOTARGET, V6, P7084, DOI 10.18632/oncotarget.3054; Zhou B, 2018, J CELL BIOCHEM, V119, P9730, DOI 10.1002/jcb.27290; Zhou KR, 2017, NUCLEIC ACIDS RES, V45, pD43, DOI 10.1093/nar/gkw965; Zhou M, 2016, SCI REP-UK, V6, DOI 10.1038/srep31038	41	2	2	3	4	FRONTIERS MEDIA SA	LAUSANNE	AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND		1664-8021		FRONT GENET	Front. Genet.	MAR 18	2020	11								245	10.3389/fgene.2020.00245			11	Genetics & Heredity	Science Citation Index Expanded (SCI-EXPANDED)	Genetics & Heredity	KZ7YN	WOS:000523475900001	32265986	Green Published, gold			2022-04-25	
J	Lin, WS; Leland, JV; Ho, CT; Pan, MH				Lin, Wei-Sheng; Leland, Jane Valorie; Ho, Chi-Tang; Pan, Min-Hsiung			Occurrence, Bioavailability, Anti-inflammatory, and Anticancer Effects of Pterostilbene	JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY			English	Review						pterostilbene; bioavailability; chemoprevention; anti-inflammation; anticancer	SIGNAL-TRANSDUCTION PATHWAYS; CANCER STEM-CELLS; IN-VITRO; COLON CARCINOGENESIS; RESVERATROL METABOLITES; MOLECULAR-MECHANISMS; TRANS-RESVERATROL; CYCLE ARREST; KAPPA-B; APOPTOSIS	Supplementation with natural compounds found in fruits and vegetables has long been associated with a reduced risk of several types of cancer. Pterostilbene is a natural stilbenoid and a dimethylated analogue of resveratrol which is found primarily in blueberries. Pterostilbene exhibits a range of pharmacological properties, particularly anti-inflammatory and anticancer effects. Due to two methoxy groups in its skeleton, pterostilbene is more lipophilic than resveratrol and thus possesses higher intestinal permeability and cellular uptake and enhanced stability. Moreover, pterostilbene exhibits less toxicity and fewer adverse effects, providing it with superior potential in cancer chemoprevention and chemotherapy applications. Numerous research studies have demonstrated that pterostilbene possesses detoxification activities, mediating the anti-inflammation response, regulating the cell cycle, augmenting apoptosis, enhancing autophagy, and inhibiting tumor angiogenesis, invasion, and metastasis by modulating signal transduction pathways which block multiple stages of carcinogenesis. In this review, we illustrate that pterostilbene is a natural compound having bioavailability. The extensive metabolism of pterostilbene will be discussed. We also summarize recent research on pterostilbene's anti-inflammatory and anticancer properties in the multistage carcinogenesis process and related molecular mechanism and conclude that it should contribute to improved cancer management.	[Lin, Wei-Sheng; Pan, Min-Hsiung] Natl Taiwan Univ, Inst Food Sci & Technol, Taipei 10617, Taiwan; [Leland, Jane Valorie] Leland Global Enterprises LLC, Wilmette, IL 60091 USA; [Pan, Min-Hsiung] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 40402, Taiwan; [Pan, Min-Hsiung] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung 41354, Taiwan; [Ho, Chi-Tang] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08901 USA		Pan, MH (corresponding author), Natl Taiwan Univ, Inst Food Sci & Technol, Taipei 10617, Taiwan.; Pan, MH (corresponding author), China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 40402, Taiwan.; Pan, MH (corresponding author), Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung 41354, Taiwan.; Ho, CT (corresponding author), Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08901 USA.	ho@aesop.rutgers.edu; mhpan@ntu.edu.tw	Pan, Min-Hsiung/AAT-8865-2021	Pan, Min-Hsiung/0000-0002-5188-7030; Ho, Chi-Tang/0000-0001-8273-2085	Ministry of Science and Technology [108-2321-B-002-020, 108-2320-B-002-016-MY3]	This study was supported by the Ministry of Science and Technology (Grants 108-2321-B-002-020 and 108-2320-B-002-016-MY3).	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Agric. Food Chem.	NOV 18	2020	68	46					12788	12799		10.1021/acs.jafc.9b07860			12	Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Agriculture; Chemistry; Food Science & Technology	OW5JM	WOS:000592922700005	32064876				2022-04-25	
J	Ghafouri-Fard, S; Abak, A; Anamag, FT; Shoorei, H; Fattahi, F; Javadinia, SA; Basiri, A; Taheri, M				Ghafouri-Fard, Soudeh; Abak, Atefe; Tondro Anamag, Farhad; Shoorei, Hamed; Fattahi, Faranak; Javadinia, Seyed Alireza; Basiri, Abbas; Taheri, Mohammad			5-Fluorouracil: A Narrative Review on the Role of Regulatory Mechanisms in Driving Resistance to This Chemotherapeutic Agent	FRONTIERS IN ONCOLOGY			English	Review						lncRNA; miRNA; fluorouracil; expression; biomarker	HEPATOCELLULAR-CARCINOMA CELLS; HUMAN COLORECTAL-CANCER; HISTONE DEACETYLASE; MULTIDRUG-RESISTANCE; 5-FU RESISTANCE; DOWN-REGULATION; PROLIFERATION; AUTOPHAGY; COMBINATION; SENSITIVITY	5-fluorouracil (5-FU) is among the mostly administrated chemotherapeutic agents for a wide variety of neoplasms. Non-coding RNAs have a central impact on the determination of the response of patients to 5-FU. These transcripts via modulation of cancer-related pathways, cell apoptosis, autophagy, epithelial-mesenchymal transition, and other aspects of cell behavior can affect cell response to 5-FU. Modulation of expression levels of microRNAs or long non-coding RNAs may be a suitable approach to sensitize tumor cells to 5-FU treatment via modulating multiple biological signaling pathways such as Hippo/YAP, Wnt/beta-catenin, Hedgehog, NF-kB, and Notch cascades. Moreover, there is an increasing interest in targeting these transcripts in various kinds of cancers that are treated by 5-FU. In the present article, we provide a review of the function of non-coding transcripts in the modulation of response of neoplastic cells to 5-FU.	[Ghafouri-Fard, Soudeh] Shahid Beheshti Univ Med Sci, Res Inst Dent Sci, Sch Dent, Dent Res Ctr, Tehran, Iran; [Abak, Atefe] Tabriz Univ Med Sci, Dept Med Genet, Fac Med, Tabriz, Iran; [Tondro Anamag, Farhad] Tabriz Univ Med Sci, Fac Med, Tabriz, Iran; [Shoorei, Hamed] Birjand Univ Med Sci, Dept Anat Sci, Fac Med, Birjand, Iran; [Fattahi, Faranak] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA; [Fattahi, Faranak] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA; [Javadinia, Seyed Alireza] Sabzevar Univ Med Sci, Cellular & Mol Res Ctr, Sabzevar, Iran; [Basiri, Abbas; Taheri, Mohammad] Shahid Beheshti Univ Med Sci, Urol & Nephrol Res Ctr, Tehran, Iran		Taheri, M (corresponding author), Shahid Beheshti Univ Med Sci, Urol & Nephrol Res Ctr, Tehran, Iran.	mohammad.taheri@sbmu.ac.ir	Shoorei, Hamed/J-5929-2019; Basiri, Abbas/AAW-3718-2021	Shoorei, Hamed/0000-0002-7762-5362; 			Akao Y, 2011, CANCER LETT, V300, P197, DOI 10.1016/j.canlet.2010.10.006; 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Oncol.	APR 19	2021	11								658636	10.3389/fonc.2021.658636			21	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	RW1WW	WOS:000646315300001	33954114	gold, Green Published			2022-04-25	
J	Lemke, D; Pledl, HW; Zorn, M; Jugold, M; Green, E; Blaes, J; Low, S; Hertenstein, A; Ott, M; Sahm, F; Steffen, AC; Weiler, M; Winkler, F; Platten, M; Dong, Z; Wick, W				Lemke, Dieter; Pledl, Hans-Werner; Zorn, Markus; Jugold, Manfred; Green, Ed; Blaes, Jonas; Loew, Sarah; Hertenstein, Anne; Ott, Martina; Sahm, Felix; Steffen, Ann-Catherine; Weiler, Markus; Winkler, Frank; Platten, Michael; Dong, Zhen; Wick, Wolfgang			Slowing down glioblastoma progression in mice by running or the anti-malarial drug dihydroartemisinin? Induction of oxidative stress in murine glioblastoma therapy	ONCOTARGET			English	Article						dihydroartemisinin; glioblastoma; physical exercises (PE); therapy; physical exercise	TUMOR-BEARING RATS; CELLS IN-VITRO; GLIOMA-CELLS; PHYSICAL-ACTIVITY; BREAST-CANCER; STEM-CELLS; RECURRENT GLIOBLASTOMA; EXERCISE PROGRAM; TEMOZOLOMIDE; AUTOPHAGY	Influencing cancer metabolism by lifestyle changes is an attractive strategy as - if effective - exercise-induced problems may be less severe than those induced by classical anti-cancer therapies. Pursuing this idea, clinical trials evaluated the benefit of e.g. different diets such as the ketogenic diet, intermittent caloric restriction and physical exercise (PE) in the primary and secondary prevention of different cancer types. PE proved to be beneficial in the context of breast and colon cancer. Glioblastoma has a dismal prognosis, with an average overall survival of about one year despite maximal safe resection, concomitant radiochemotherapy with temozolomide followed by adjuvant temozolomide therapy. Here, we focused on the influence of PE as an isolated and adjuvant treatment in murine GB therapy. PE did not reduce toxic side effects of chemotherapy in mice administered in a dose escalating scheme as shown before for starvation. Although regular treadmill training on its own had no obvious beneficial effects, its combination with temozolomide was beneficial in the treatment of glioblastoma-bearing mice. As PE might partly act through the induction of reactive oxygen species, dihydroartemisinin - an approved anti-malarial drug which induces oxidative stress in glioma cells - was further evaluated in vitro and in vivo. Dihydroartemisinin showed anti-glioma activity by promoting autophagy, reduced the clonogenic survival and proliferation capacity of glioma cells, and prolonged the survival of tumor bearing mice. Using the reactive oxygen species scavenger n-acetyl-cysteine these effects were in part reversible, suggesting that dihydroartemisinin partly acts through the generation of reactive oxygen species.	[Lemke, Dieter; Pledl, Hans-Werner; Green, Ed; Blaes, Jonas; Loew, Sarah; Hertenstein, Anne; Ott, Martina; Sahm, Felix; Steffen, Ann-Catherine; Weiler, Markus; Winkler, Frank; Platten, Michael; Wick, Wolfgang] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany; [Lemke, Dieter; Pledl, Hans-Werner; Blaes, Jonas; Loew, Sarah; Hertenstein, Anne; Steffen, Ann-Catherine; Weiler, Markus; Winkler, Frank; Wick, Wolfgang] German Canc Res Ctr, Clin Cooperat Unit Neurooncol, Heidelberg, Germany; [Lemke, Dieter; Pledl, Hans-Werner; Loew, Sarah; Hertenstein, Anne; Weiler, Markus; Winkler, Frank; Platten, Michael; Wick, Wolfgang] Heidelberg Univ, German Canc Res Ctr DKFZ, Neurol Clin, Heidelberg, Germany; [Lemke, Dieter; Pledl, Hans-Werner; Loew, Sarah; Hertenstein, Anne; Weiler, Markus; Winkler, Frank; Platten, Michael; Wick, Wolfgang] Heidelberg Univ, German Canc Res Ctr DKFZ, Natl Ctr Tumor Dis, Heidelberg, Germany; [Zorn, Markus] German Canc Res Ctr, Cent Lab Heidelberg Univ Hosp, Heidelberg, Germany; [Jugold, Manfred] German Canc Res Ctr, Core Facil Small Anim Imaging Ctr, Heidelberg, Germany; [Green, Ed; Ott, Martina; Platten, Michael] German Canc Res Ctr, Clin Cooperat Unit Neuroimmunol & Brain Tumor Imm, Heidelberg, Germany; [Sahm, Felix] Heidelberg Univ, Inst Pathol, Dept Neuropathol, German Canc Res Ctr DKFZ, Heidelberg, Germany; [Sahm, Felix] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, Heidelberg, Germany; [Dong, Zhen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Neurosurg, Wuhan, Peoples R China		Wick, W (corresponding author), German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.; Wick, W (corresponding author), German Canc Res Ctr, Clin Cooperat Unit Neurooncol, Heidelberg, Germany.; Wick, W (corresponding author), Heidelberg Univ, German Canc Res Ctr DKFZ, Neurol Clin, Heidelberg, Germany.; Wick, W (corresponding author), Heidelberg Univ, German Canc Res Ctr DKFZ, Natl Ctr Tumor Dis, Heidelberg, Germany.; Dong, Z (corresponding author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Neurosurg, Wuhan, Peoples R China.	dongz@tjh.tjmu.edu.cn; wolfgang.wick@med.uni-heidelberg.de	Platten, Michael/F-2902-2013; Sahm, Felix/W-8050-2019; Wick, Wolfgang/AAA-2545-2020; Dong, Zhen/K-8432-2015	Platten, Michael/0000-0002-4746-887X; Sahm, Felix/0000-0001-5441-1962; Wick, Wolfgang/0000-0002-6171-634X; Dong, Zhen/0000-0002-8801-9966; Winkler, Frank/0000-0003-4892-6104	German Research FoundationGerman Research Foundation (DFG) [SFB938 TPK]	Supported by German Research Foundation (SFB938 TPK) to M.P. and W.W.	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J	Christodoulou, EG; Yang, H; Lademann, F; Pilarsky, C; Beyer, A; Schroeder, M				Christodoulou, Eleni G.; Yang, Hai; Lademann, Franziska; Pilarsky, Christian; Beyer, Andreas; Schroeder, Michael			Detection of COPB2 as a KRAS synthetic lethal partner through integration of functional genomics screens	ONCOTARGET			English	Article						KRAS; synthetic lethal partner; ranking; rank aggregation; functional screens	RNA INTERFERENCE; COLORECTAL-CANCER; RAS; REVEALS; AUTOPHAGY; IDENTIFICATION; INHIBITION; CARCINOMA; TUMORS; CELLS	Mutated KRAS plays an important role in many cancers. Although targeting KRAS directly is difficult, indirect inactivation via synthetic lethal partners (SLPs) is promising. Yet to date, there are no SLPs from high-throughput RNAi screening, which are supported by multiple screens. Here, we address this problem by aggregating and ranking data over three independent high-throughput screens. We integrate rankings by minimizing the displacement and by considering established methods such as RIGER and RSA. Our meta analysis reveals COPB2 as a potential SLP of KRAS with good support from all three screens. COPB2 is a coatomer subunit and its knock down has already been linked to disabled autophagy and reduced tumor growth. We confirm COPB2 as SLP in knock down experiments on pancreas and colorectal cancer cell lines. Overall, consistent integration of high throughput data can generate candidate synthetic lethal partners, which individual screens do not uncover. Concretely, we reveal and confirm that COPB2 is a synthetic lethal partner of KRAS and hence a promising cancer target. Ligands inhibiting COPB2 may, therefore, be promising new cancer drugs.	[Christodoulou, Eleni G.; Beyer, Andreas; Schroeder, Michael] Tech Univ Dresden, Biotechnol Ctr, Dresden, Germany; [Christodoulou, Eleni G.] Natl Canc Ctr Singapore, Dept Med Oncol, Singapore, Singapore; [Yang, Hai; Pilarsky, Christian] Univ Klinikum Erlangen, Translat Res Ctr, Chirurg Klin, Erlangen, Germany; [Lademann, Franziska; Pilarsky, Christian] Tech Univ Dresden, Med Fak Carl Gustav Carus, Dresden, Germany; [Beyer, Andreas] Univ Cologne, Cellular Networks & Syst Biol, Cologne, Germany		Beyer, A; Schroeder, M (corresponding author), Tech Univ Dresden, Biotechnol Ctr, Dresden, Germany.; Beyer, A (corresponding author), Univ Cologne, Cellular Networks & Syst Biol, Cologne, Germany.	andreas.beyer@uni-koeln.de; ms@biotec.tu-dresden.de	Beyer, Andreas/A-3352-2009; Beyer, Andreas/AAQ-5519-2020	Beyer, Andreas/0000-0002-3891-2123; Beyer, Andreas/0000-0002-3891-2123; Pilarsky, Christian/0000-0002-7968-3283; Lademann, Franziska/0000-0003-1059-5506			Bailey P, 2016, NATURE, V531, P47, DOI 10.1038/nature16965; Barbie DA, 2009, NATURE, V462, P108, DOI 10.1038/nature08460; Beyer A, 2007, NAT REV GENET, V8, P699, DOI 10.1038/nrg2144; Biankin AV, 2012, NATURE, V491, P399, DOI 10.1038/nature11547; Birmingham A, 2009, NAT METHODS, V6, P569, DOI 10.1038/nmeth.1351; BOS JL, 1989, CANCER RES, V49, P4682; Brannon AR, 2014, GENOME BIOL, V15, DOI 10.1186/s13059-014-0454-7; Burada F, 2015, WORLD J GASTRO ONCOL, V7, P271, DOI 10.4251/wjgo.v7.i11.271; Cerami E., 2012, CANC DISCOVERY, V2; Claerhout S, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0039400; Deer EL, 2010, PANCREAS, V39, P425, DOI 10.1097/MPA.0b013e3181c15963; Dietlein F, 2015, CELL, V162, P146, DOI 10.1016/j.cell.2015.05.053; Downward J, 2003, NAT REV CANCER, V3, P11, DOI 10.1038/nrc969; Dwork C., 2001, SYST RES, V13, P86; Franceschini A, 2014, P NATL ACAD SCI USA, V111, P4548, DOI 10.1073/pnas.1402353111; Gao JJ, 2013, SCI SIGNAL, V6, DOI 10.1126/scisignal.2004088; Gelmon KA, 2011, LANCET ONCOL, V12, P852, DOI 10.1016/S1470-2045(11)70214-5; Giannakis M, 2016, CELL REP, V15, P857, DOI 10.1016/j.celrep.2016.03.075; Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013; Hernandez-Valladares M, 2015, SCI REP-UK, V5, DOI 10.1038/srep17307; Ihle NT, 2012, JNCI-J NATL CANCER I, V104, P228, DOI 10.1093/jnci/djr523; Jackson AL, 2003, NAT BIOTECHNOL, V21, P635, DOI 10.1038/nbt831; Kim HS, 2013, CELL, V155, P552, DOI 10.1016/j.cell.2013.09.041; Konig R, 2007, NAT METHODS, V4, P847, DOI 10.1038/NMETH1089; Luo B, 2008, P NATL ACAD SCI USA, V105, P20380, DOI 10.1073/pnas.0810485105; Luo J, 2009, CELL, V137, P835, DOI 10.1016/j.cell.2009.05.006; Mitchell A, 2015, NUCLEIC ACIDS RES, V43, pD213, DOI 10.1093/nar/gku1243; Muzny DM, 2012, NATURE, V487, P330, DOI 10.1038/nature11252; Ostrem JM, 2013, NATURE, V503, P548, DOI 10.1038/nature12796; Pihur V, 2009, BMC BIOINFORMATICS, V10, DOI 10.1186/1471-2105-10-62; Razi M, 2009, J CELL BIOL, V185, P305, DOI 10.1083/jcb.200810098; Reinhardt HC, 2009, CELL CYCLE, V8, P3112, DOI 10.4161/cc.8.19.9626; Ruckert F, 2012, J SURG RES, V172, P29, DOI 10.1016/j.jss.2011.04.021; Safran M, 2010, GENECARDS VERSION 3; Sakitani K, 2015, BMC CANCER, V15, DOI 10.1186/s12885-015-1789-5; Schaaf G, 2010, CANCER RES, V70, P762, DOI 10.1158/0008-5472.CAN-09-2532; Scholl C, 2009, CELL, V137, P821, DOI 10.1016/j.cell.2009.03.017; Seshagiri S, 2012, NATURE, V488, P660, DOI 10.1038/nature11282; Singh A, 2005, FASEB J, V19, P161, DOI 10.1096/fj.04-2584hyp; Singh A, 2009, CANCER CELL, V15, P489, DOI 10.1016/j.ccr.2009.03.022; Steckel M, 2012, CELL RES, V22, P1227, DOI 10.1038/cr.2012.82; Tanida Isei, 2008, V445, P77, DOI 10.1007/978-1-59745-157-4_4; Unniyampurath U, 2016, INT J MOL SCI, V17, DOI 10.3390/ijms17030291; van Dam EM, 2006, INT J BIOCHEM CELL B, V38, P1841, DOI 10.1016/j.biocel.2006.04.006; Wang Y, 2010, ONCOGENE, V29, P4658, DOI 10.1038/onc.2010.218; Ward AF, 2012, BLOOD, V120, P3397, DOI 10.1182/blood-2012-05-378596; Weidle UH, 2011, CANCER GENOM PROTEOM, V8, P159; Witkiewicz AK, 2015, NAT COMMUN, V6, DOI 10.1038/ncomms7744; Yang A, 2014, CANCER DISCOV, V4, P905, DOI 10.1158/2159-8290.CD-14-0362; Young A, 2009, ADV CANCER RES, V102, P1, DOI 10.1016/S0065-230X(09)02001-6	50	4	5	0	4	IMPACT JOURNALS LLC	ORCHARD PARK	6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA		1949-2553		ONCOTARGET	Oncotarget	MAY 23	2017	8	21					34283	34297		10.18632/oncotarget.16079			15	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	EV8RY	WOS:000402051700027	28415695	Green Published, Green Submitted, gold			2022-04-25	
J	Xie, XL; Liu, YB; Liu, YP; Du, BL; Li, Y; Han, M; Li, BH				Xie, Xiao-Li; Liu, Ya-Bin; Liu, Yue-Ping; Du, Bin-Liang; Li, Yang; Han, Mei; Li, Bing-Hui			Reduced expression of SM22 is correlated with low autophagy activity in human colorectal cancer	PATHOLOGY RESEARCH AND PRACTICE			English	Article						SM22; Autophagy; p62; Colorectal cancer	SMOOTH-MUSCLE-CELLS; PROSTATE-CANCER; TRANSGELIN; PROTEIN; P62; SUPPRESSOR; BREAST; TUMORIGENESIS; ALPHA; P53	Colorectal cancer (CRC) is a common malignancy with a high incidence and mortality rate. Recent studies have pointed to deregulation of autophagy as a novel pathogenesis of human malignancy. SM22 is considered as a tumor suppressor. The aim of the present study was to evaluate the correlation of the SM22 expression level with the autophagy activity and the clinical characteristics in human CRC tissues. The expressions of SM22 and p62, a biomarker of autophagy activity, in paired tumor and adjacent non-tumor tissues from 43 patients with colorectal cancer were detected by western blot and immunohistochemical staining, respectively. The results showed that the SM22 level decreased significantly in 81.4% CRC tissues, while the expression of p62 increased in 79.1% cases. There was a negative correlation between p62 and SM22 expressions in colorectal cancer tissues (p = 0.004). Similarly, the negative correlation between 5M22 and p62 was verified in human CRC cell lines. The data suggest that the autophagy activity decreased in human CRC, which was associated with reduction in SM22 expression. However, the expression of SM22 was not associated with the gender, tumor site and Duke's stage of the patients. In conclusion, our findings suggest that the disruption of SM22 may be involved in tumorigenesis in CRC. The autophagic activity may be suppressed in human CRC, and SM22 may act as a positive regulator in the processes of autophagy. (C) 2013 Elsevier GmbH. All rights reserved.	[Xie, Xiao-Li; Han, Mei] Hebei Med Univ, Coll Basic Med, Key Lab Med Biotechnol Hebei Prov,Minist Educ, Dept Biochem & Mol Biol,Key Lab Neural & Vasc Bio, Shijiazhuang 050017, Peoples R China; [Liu, Ya-Bin; Du, Bin-Liang; Li, Yang; Li, Bing-Hui] Hebei Med Univ, Affiliated Hosp 4, Dept Surg, Shijiazhuang 050017, Peoples R China; [Liu, Yue-Ping] Hebei Med Univ, Affiliated Hosp 4, Dept Pathol, Shijiazhuang 050017, Peoples R China		Han, M (corresponding author), Hebei Med Univ, Coll Basic Med, Key Lab Med Biotechnol Hebei Prov,Minist Educ, Dept Biochem & Mol Biol,Key Lab Neural & Vasc Bio, Shijiazhuang 050017, Peoples R China.	hanmei@hebmu.edu.cn; lbh58@hebmu.edu.cn		liu, yabin/0000-0003-4970-7069			Assinder SJ, 2009, INT J BIOCHEM CELL B, V41, P482, DOI 10.1016/j.biocel.2008.02.011; Bjorkoy G, 2005, J CELL BIOL, V171, P603, DOI 10.1083/jcb.200507002; Bozkurt KK, 2012, PATHOL RES PRACT, V208, P133, DOI 10.1016/j.prp.2011.12.015; Dong LH, 2010, ARTERIOSCL THROM VAS, V30, P683, DOI 10.1161/ATVBAHA.109.200501; Duran A, 2008, CANCER CELL, V13, P343, DOI 10.1016/j.ccr.2008.02.001; Gerolymos M, 2011, NEPHRON CLIN PRACT, V119, pC74, DOI 10.1159/000324655; Gimona M, 2003, MOL BIOL CELL, V14, P2482, DOI 10.1091/mbc.E02-11-0743; Han M, 2009, LIFE SCI, V84, P394, DOI 10.1016/j.lfs.2008.11.017; Ichimura Y, 2010, SEMIN IMMUNOPATHOL, V32, P431, DOI 10.1007/s00281-010-0220-1; Jaakkola PM, 2009, AUTOPHAGY, V5, P410, DOI 10.4161/auto.5.3.7823; Mascaux C, 2003, EUR RESPIR J, V21, P753, DOI 10.1183/09031936.03.00090202; Mathew R, 2011, CURR OPIN GENET DEV, V21, P113, DOI 10.1016/j.gde.2010.12.008; Mathew R, 2009, CELL, V137, P1062, DOI 10.1016/j.cell.2009.03.048; Mizushima N, 2007, AUTOPHAGY, V3, P542, DOI 10.4161/auto.4600; Mizushima N, 2010, CELL, V140, P313, DOI 10.1016/j.cell.2010.01.028; Prasad PD, 2010, CELL TISSUE RES, V339, P337, DOI 10.1007/s00441-009-0902-y; Rosenfeldt MT, 2011, CARCINOGENESIS, V32, P955, DOI 10.1093/carcin/bgr031; Roy S, 2010, SEMIN IMMUNOPATHOL, V32, P383, DOI 10.1007/s00281-010-0213-0; Shields JM, 2002, J BIOL CHEM, V277, P9790, DOI 10.1074/jbc.M110086200; Su YX, 2005, CLIN IMMUNOL, V116, P118, DOI 10.1016/j.clim.2005.04.004; Thompson O, 2012, BMC CELL BIOL, V13, DOI 10.1186/1471-2121-13-1; Wulfkuhle JD, 2002, CANCER RES, V62, P6740; Yang ZM, 2007, MOL ENDOCRINOL, V21, P343, DOI 10.1210/me.2006-0104; Yeo M, 2010, CANCER-AM CANCER SOC, V116, P2581, DOI 10.1002/cncr.25003; Yu HY, 2008, FASEB J, V22, P1778, DOI 10.1096/fj.07-083857; Zhang JCL, 2001, MOL CELL BIOL, V21, P1336, DOI 10.1128/MCB.2001.21.4.1336-1344.2001; Zhang ZW, 2010, ASIAN J ANDROL, V12, P186, DOI 10.1038/aja.2009.76; Zhao L, 2009, MODERN PATHOL, V22, P786, DOI 10.1038/modpathol.2009.29	28	10	12	0	2	ELSEVIER GMBH, URBAN & FISCHER VERLAG	JENA	OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY	0344-0338			PATHOL RES PRACT	Pathol. Res. Pract.		2013	209	4					237	243		10.1016/j.prp.2013.02.007			7	Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Pathology	152PN	WOS:000319543700007	23538046				2022-04-25	
J	Barone, R; Bavisotto, CC; Rappa, F; Gargano, ML; Macaluso, F; Paladino, L; Vitale, AM; Alfano, S; Campanella, C; Gorska, M; Di Felice, V; Cappello, F; Venturella, G; Gammazza, AM				Barone, Rosario; Caruso Bavisotto, Celeste; Rappa, Francesca; Gargano, Maria Letizia; Macaluso, Filippo; Paladino, Letizia; Vitale, Alessandra Maria; Alfano, Stefano; Campanella, Claudia; Gorska, Magdalena; Di Felice, Valentina; Cappello, Francesco; Venturella, Giuseppe; Marino Gammazza, Antonella			JNK pathway and heat shock response mediate the survival of C26 colon carcinoma bearing mice fed with the mushroom Pleurotus eryngii var. eryngii without affecting tumor growth or cachexia	FOOD & FUNCTION			English	Article								In the last few years, there has been emerging interest in developing treatments against human diseases using natural bioactive content. Here, the powder of the edible mushroom Pleurotus eryngii var. eryngii was mixed with the normal diet of mice bearing C26 colon carcinoma. Interestingly, it was evidenced by a significant increase in the survival rate of C26 tumor-bearing mice accompanied by a significant increase in Hsp90 and Hsp27 protein levels in the tumors. These data were paralleled by a decrease in Hsp60 levels. The mushroom introduced in the diet induced the inhibition of the transcription of the pro-inflammatory cytokines IL-6 and IL-1 exerting an anti-inflammatory action. The effects of the mushroom were mediated by the activation of c-Jun NH2-terminal kinases as a result of metabolic stress induced by the micronutrients introduced in the diet. In the tumors of C26 bearing mice fed with Pleurotus eryngii there was also a decreased expression of the mitotic regulator survivin and the anti-apoptotic factor Bcl-xL as well as an increase in the expression levels of Atg7, a protein that drives autophagy. In our hypothesis the interplay of these molecules favored the survival of the mice fed with the mushroom. These data are promising for the introduction of Pleurotus eryngii as a dietary supplement or as an adjuvant in anti-cancer therapy.	[Barone, Rosario; Caruso Bavisotto, Celeste; Rappa, Francesca; Paladino, Letizia; Vitale, Alessandra Maria; Alfano, Stefano; Campanella, Claudia; Di Felice, Valentina; Cappello, Francesco; Marino Gammazza, Antonella] Univ Palermo, Dept Biomed Neurosci & Adv Diagnost, Palermo, Italy; [Gargano, Maria Letizia; Venturella, Giuseppe] Univ Palermo, Dept Agr Food & Forest Sci, Palermo, Italy; [Gargano, Maria Letizia] Univ Bari Aldo Moro, Dept Agr & Environm Sci, Bari, Italy; [Gargano, Maria Letizia; Venturella, Giuseppe] Italian Soc Med Mushrooms, Pisa, Italy; [Macaluso, Filippo] eCampus Univ, Novedrate, CO, Italy; [Gorska, Magdalena] Med Univ Gdansk, Dept Med Chem, Gdansk, Poland		Gammazza, AM (corresponding author), Univ Palermo, Dept Biomed Neurosci & Adv Diagnost, Palermo, Italy.	antonella.marinogammazza@unipa.it	Vitale, Alessandra Maria/ABD-7894-2021; barone, rosario/ABA-6758-2021; Di Felice, Valentina/AAG-3740-2021; Gargano, Maria Letizia/G-8251-2015	Di Felice, Valentina/0000-0002-4132-1260; Gargano, Maria Letizia/0000-0002-0511-5363; Paladino, Letizia/0000-0001-8037-7761; Vitale, Alessandra Maria/0000-0002-7566-4309			Al-Kandari N, 2019, MOLECULES, V24, DOI 10.3390/molecules24183333; Aulino P, 2010, BMC CANCER, V10, DOI 10.1186/1471-2407-10-363; Aung TN, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18030656; Barone R, 2017, J CELL PHYSIOL, V232, P1086, DOI 10.1002/jcp.25511; Barone R, 2016, SCI REP-UK, V6, DOI 10.1038/srep19781; Bavisotto CC, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20184496; Bavisotto CC, 2017, J INORG BIOCHEM, V170, P8, DOI 10.1016/j.jinorgbio.2017.02.004; Bayisotto CC, 2020, FRONT MOL BIOSCI, V7, DOI 10.3389/fmolb.2020.00095; Cappello F, 2005, BMC CANCER, V5, DOI 10.1186/1471-2407-5-139; Cappello F, 2006, CANCER-AM CANCER SOC, V107, P2417, DOI 10.1002/cncr.22265; Carmi Y, 2009, J IMMUNOL, V183, P4705, DOI 10.4049/jimmunol.0901511; Cateni F, 2020, INT J MED MUSHROOMS, V22, P431, DOI 10.1615/IntJMedMushrooms.2020034539; Cateni F, 2018, INT J MED MUSHROOMS, V20, P717, DOI [10.1615/IntJMedMushrooms.2018027011, 10.1615/intjmedmushrooms.2018027011]; 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APR 7	2021	12	7					3083	3095		10.1039/d0fo03171b			13	Biochemistry & Molecular Biology; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Food Science & Technology	RM3XC	WOS:000639596100021	33720221				2022-04-25	
J	Yang, YP; Zhu, F; Wang, QM; Ding, Y; Ying, RB; Zeng, LH				Yang, Youping; Zhu, Feng; Wang, Qingmei; Ding, Yan; Ying, Rongbiao; Zeng, Linghui			Inhibition of EZH2 and EGFR produces a synergistic effect on cell apoptosis by increasing autophagy in gastric cancer cells	ONCOTARGETS AND THERAPY			English	Article						EZH2; EGFR; autophagy; mTOR signaling; gastric cancer	COLON-CANCER; EXPRESSION; PROTEIN; GROWTH; GEFITINIB; THERAPY; FAMILY; TUMOR; PANEL	Background: Numerous reports have shown that a combination of two or more drugs leads to better cancer treatment. Inhibitors of zeste homology 2 and epidermal growth factor receptor have been widely used in cancer treatments. However, the mechanisms of the combined use of these two drugs remain elusive. Methods: Sul forhodamine B assays and Alexa Fluor (R)-488 Annexin V/Dead Cell Apoptosis Kit were used to detect the cell proliferation and cell apoptosis in vitro, respectively. Western blotting analysis was used to detect the relative protein expression, and xenografted tumor was generated in nude mice to evaluate the effect in vivo. Results: Treatment with either Gefitinib ranging from 0 to 12.5 mu M or GSK126 ranging from 0 to 8.3 mu M caused adore-dependent decrease in the cell survival fraction, and the combination of Gefitinib at 12.5 mu M and GSK126 at 8.3 mu M caused further significant decrease. The combination indexes were 0.061, 0.591, 0.713, and 0.371 for MGC803, A549, PC-3, and MDB-MA-231, respectively. In MGC803 cells, the combination of GSK126 and Gefitinib synergistically induced cell apoptosis (56.2%), which was markedly higher as compared to either drug alone (7.6% and 10.6%, P<0.05). Treatment with either Gefitinib or GSK126 alone induced a significant increase in cell apoptosis in LC3-II and p-ULK, whereas the combination of the two induced a further increase. Pretreatment with an autophagy inhibitor, 3-methyladenine, prevented the apoptosis induced by the combined use of Gefitinib and GSK126. In addition, the combined use of Gefitinib and GSK126 also inhibited the activation of mammalian target of rapamycin signaling pathway. Furthermore, the combined use of GSK126 and Gefitinib synergistically inhibited xenografted tumor proliferation. Conclusion: The combined use of GSK126 and Gefitinib exerts a synergic effect on tumor growth inhibition both in vitro and in vivo through inducing autophagy and promoting apoptosis. Therefore, GSK126 and Gefitinib in combination may be considered as a potential strategy in treating solid tumor clinically.	[Yang, Youping] First Peoples Hosp Wenling City, Dept Pathol, Wenling City 317500, Zhejiang, Peoples R China; [Yang, Youping; Ding, Yan; Ying, Rongbiao] Taizhou Canc Hosp, Dept Surg Oncol, Wenling City 317500, Zhejiang, Peoples R China; [Zhu, Feng; Wang, Qingmei; Zeng, Linghui] Zhejiang Univ City Coll, Dept Pharmacol, 50 Huzhou Rd, Hangzhou 310015, Zhejiang, Peoples R China		Zeng, LH (corresponding author), Zhejiang Univ City Coll, Dept Pharmacol, 50 Huzhou Rd, Hangzhou 310015, Zhejiang, Peoples R China.	zenglh@zucc.edu.cn			Foundation of Zhejiang Health Bureau [2015 KYA148, 2015RCB004]; Zhejiang Provincial Foundation of National Science [LY12H16005]	Research reported in this publication was supported by the Foundation of Zhejiang Health Bureau (2015 KYA148, 2015RCB004) and Zhejiang Provincial Foundation of National Science (LY12H16005).	Azad N, 2013, NAT REV CLIN ONCOL, V10, P256, DOI 10.1038/nrclinonc.2013.42; Booth LA, 2014, CELL SIGNAL, V26, P549, DOI 10.1016/j.cellsig.2013.11.028; Charalampakis N, 2018, CANCER MED-US, V7, P123, DOI 10.1002/cam4.1274; Chen YT, 2016, CANCER CHEMOTH PHARM, V77, P757, DOI 10.1007/s00280-016-2990-1; Chou TC, 2010, CANCER RES, V70, P440, DOI 10.1158/0008-5472.CAN-09-1947; Dhillon S, 2015, TARGET ONCOL, V10, P153, DOI 10.1007/s11523-015-0358-9; Girgert R, 2017, ONCOL REP, V37, P1212, DOI 10.3892/or.2016.5306; Grinshtein N, 2016, ONCOTARGET, V7, P59360, DOI 10.18632/oncotarget.10661; Jiang T, 2016, ONCOTARGET, V7, P4584, DOI 10.18632/oncotarget.6612; Katona BW, 2014, CANCER BIOL THER, V15, P1677, DOI 10.4161/15384047.2014.972776; Khan M, 2015, LAB INVEST, V95, P1278, DOI 10.1038/labinvest.2015.104; Kim KH, 2016, NAT MED, V22, P128, DOI 10.1038/nm.4036; Koppens MAJ, 2016, ONCOTARGET, V7, P69816, DOI 10.18632/oncotarget.12002; McCabe MT, 2012, NATURE, V492, P108, DOI 10.1038/nature11606; Morishita A, 2014, WORLD J GASTROENTERO, V20, P4536, DOI 10.3748/wjg.v20.i16.4536; Oral O, 2016, HISTOL HISTOPATHOL, V31, P479, DOI 10.14670/HH-11-714; Pei JJ, 2016, AUTOPHAGY, V12, P1738, DOI 10.1080/15548627.2016.1196318; Petraglia Francesca, 2018, Oncotarget, V9, P25630, DOI 10.18632/oncotarget.25428; Prahallad A, 2012, NATURE, V483, P100, DOI 10.1038/nature10868; Ravegnini G, 2017, AUTOPHAGY, V13, P452, DOI 10.1080/15548627.2016.1256522; Riely GJ, 2008, LUNG CANCER, V60, pS19, DOI 10.1016/S0169-5002(08)70101-6; Rogawski DS, 2016, FUTURE MED CHEM, V8, P1589, DOI 10.4155/fmc-2016-0071; Rubin BP, 2010, AUTOPHAGY, V6, P1190, DOI 10.4161/auto.6.8.13430; Rubinstein AD, 2011, MOL CELL, V44, P698, DOI 10.1016/j.molcel.2011.10.014; Rusnak DW, 2007, CELL PROLIFERAT, V40, P580, DOI 10.1111/j.1365-2184.2007.00455.x; Song ZD, 2017, EUR J MED CHEM, V133, P329, DOI 10.1016/j.ejmech.2017.03.083; Valentini AM, 2008, CURR OPIN MOL THER, V10, P124; Wieduwilt MJ, 2008, CELL MOL LIFE SCI, V65, P1566, DOI 10.1007/s00018-008-7440-8; Zeng DL, 2017, ONCOTARGET, V8, P3396, DOI 10.18632/oncotarget.13773; Zhu J, 2017, CELL DEATH DIS, V8, DOI 10.1038/cddis.2017.488	30	16	17	1	2	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1178-6930			ONCOTARGETS THER	OncoTargets Ther.		2018	11						8455	8463		10.2147/OTT.S186498			9	Biotechnology & Applied Microbiology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	HD0UU	WOS:000452225100001	30555238	Green Published, Green Submitted, gold			2022-04-25	
J	Asakura, K; Izumi, Y; Yamamoto, M; Yamauchi, Y; Kawai, K; Serizawa, A; Mizushima, T; Ohmura, M; Kawamura, M; Wakui, M; Adachi, T; Nakamura, M; Suematsu, M; Nomori, H				Asakura, Keisuke; Izumi, Yotaro; Yamamoto, Michiko; Yamauchi, Yoshikane; Kawai, Kenji; Serizawa, Akihiko; Mizushima, Tomoko; Ohmura, Mitsuyo; Kawamura, Masafumi; Wakui, Masatoshi; Adachi, Takeshi; Nakamura, Masato; Suematsu, Makoto; Nomori, Hiroaki			The Cytostatic Effects of Lovastatin on ACC-MESO-1 Cells	JOURNAL OF SURGICAL RESEARCH			English	Article						statins; mesothelioma; autophagic changes	PHOSPHOLIPASE C-EPSILON; BREAST-CANCER CELLS; MALIGNANT MESOTHELIOMA; RHO-GTPASES; INDUCED AUTOPHAGY; NITRIC-OXIDE; IN-VIVO; INHIBITION; ACTIVATION; STATINS	Background. Malignant pleural mesothelioma is known to be widely resistant to therapy, and new treatment strategies are needed. Statins are small molecules that suppress the production of multiple hydrophobic substrates in the mevalonate pathway. Although still controversial, statins may decrease the risk of certain cancers such as colon cancer, lung cancer, and prostate cancer. Since the evaluations of the direct effect of statins on malignant mesothelioma are still few, the present study was done to evaluate the effects of lovastatin on ACC-MESO-1 cells in vivo and to investigate the potential mechanisms involved in vitro. Materials and Methods. The in vivo effect of lovastatin was evaluated using an NOD/SCID/gamma null (NOG) mouse model of human malignant mesothelioma using ACC-MESO-1 cells. Lovastatin was also applied to ACC-MESO-1 cells in vitro and the effects were observed. Results. Lovastatin administration reduced primary tumor and metastasis in the NOG mouse model of human malignant mesothelioma. In vitro studies showed that lovastatin administration induced cytostatic effects as per reduced cell viability and cell migration in ACC-MESO-1 cells. These effects were suggested to be dependent on autophagic changes rather than apoptosis. Furthermore, induction of autophagic changes by lovastatin in ACC-MESO-1 cells was independent of mTOR, and was considered to be dependent at least in part on Rac/phospholipase C/inositol 1,4,5-triphosphate axis. Conclusions. These results suggest that it may be possible to utilize statins, or other pharmacological agents that are known to induce mTOR-independent autophagy, as an adjunct to standard treatments in malignant mesothelioma. (C) 2011 Elsevier Inc. All rights reserved.	[Izumi, Yotaro] Keio Univ, Div Gen Thorac Surg, Sch Med, Dept Surg,Shinjuku Ku, Tokyo 1608582, Japan; [Asakura, Keisuke; Yamamoto, Michiko; Ohmura, Mitsuyo; Suematsu, Makoto] Keio Univ, Sch Med, Dept Biochem, Tokyo 1608582, Japan; [Wakui, Masatoshi] Keio Univ, Sch Med, Dept Lab Med, Tokyo 1608582, Japan; [Kawai, Kenji; Mizushima, Tomoko; Nakamura, Masato] Cent Inst Expt Anim, Kanagawa, Japan; [Serizawa, Akihiko] Tokai Univ Hosp, Div Diagnost Pathol, Kanagawa, Japan; [Adachi, Takeshi] Natl Def Med Sch, Dept Internal Med 1, Div Cardiol, Tokorozawa, Saitama, Japan; [Nakamura, Masato] Tokai Univ, Sch Med, Dept Pathol & Regenerat Med, Kanagawa 2591100, Japan		Izumi, Y (corresponding author), Keio Univ, Div Gen Thorac Surg, Sch Med, Dept Surg,Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.	yotaroizumi@a2.keio.jp	Suematsu, Makoto/O-5762-2018; Suematsu, Makoto/I-8135-2013; Yamauchi, Yoshikane/I-1952-2019	Suematsu, Makoto/0000-0002-7165-6336; Suematsu, Makoto/0000-0002-7165-6336; Yamauchi, Yoshikane/0000-0002-3374-2399; Asakura, Keisuke/0000-0002-4491-3456	Ministry of Education, Culture, Sports, Science, and Technology-JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [19790981]; Ministry of Education, Culture, Sports, Science and TechnologyMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT); School of Medicine, Keio University; Nateglinide Memorial Toyoshima Research and Education Fund	The authors thank Kei Tsujioka, Takayo Oba, Division of General Thoracic Surgery, and Kyoko Ishiwata, Department of Biochemistry, for their excellent technical assistance. This work was supported in part by grant in aid from the Ministry of Education, Culture, Sports, Science, and Technology-Japan to KA (no. 19790981), in part by Global COE Program for Metabolomics Systems Biology from the Ministry of Education, Culture, Sports, Science and Technology to MS, in part by School of Medicine, Keio University fund for the promotion of science to MW and YI, and in part by Nateglinide Memorial Toyoshima Research and Education Fund to TA.	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Surg. Res.	OCT	2011	170	2					E197	E209		10.1016/j.jss.2011.06.037			13	Surgery	Science Citation Index Expanded (SCI-EXPANDED)	Surgery	823NH	WOS:000295128600001	21816418				2022-04-25	
J	Delmas, D; Solary, E; Latruffe, N				Delmas, D.; Solary, E.; Latruffe, N.			Resveratrol, a Phytochemical Inducer of Multiple Cell Death Pathways: Apoptosis, Autophagy and Mitotic Catastrophe	CURRENT MEDICINAL CHEMISTRY			English	Review						Apoptosis; cancer; chemosensitization; lipid rafts; phagocytosis; resveratrol	NF-KAPPA-B; BREAST-CANCER CELLS; PROTEIN-KINASE-C; INHIBITS CYCLOOXYGENASE-2 TRANSCRIPTION; CHEMOPREVENTIVE AGENT RESVERATROL; FAS-INDEPENDENT APOPTOSIS; NATURAL-PRODUCT PRESENT; DRUG-INDUCED APOPTOSIS; COLON-CARCINOMA CELLS; NITRIC-OXIDE SYNTHASE	Cancers are the largest cause of mortality and morbidity in industrialized countries. In the field of the medicinal chemistry of natural products, numerous studies have reported interesting properties of trans-resveratrol as a chemopreventing agent against cancers, inflammation, and viral infection. Tumor growth inhibition has been linked to the ability of resveratrol to arrest cell cycle progression and to trigger cell death. This review focuses on the pathways that mediate resveratrol-induced cell death. Resveratrol impacts on the mitochondrial functions (respiratory chain, oncoproteins, gene expression, etc), in which p53 protein can be involved and its acetylated or phosphorylated forms. This polyphenol also affects death receptor distribution in ceramide-enriched membrane platforms which serve to trap and cluster receptor molecules, and facilitates the formation of a death-inducing signaling complex in the cell. To induce apoptosis, resveratrol also activates the ceramide / sphingomyelin pathway, which promotes ceramide generation and the downstream activation of kinase cascades. Resveratrol can activate alternative pathways to cell death such as those leading to autophagy, senescence or mitotic catastrophe. Furthermore, numerous attempts have been made using resveratrol analogs to improve the molecule's ability to block cell proliferation and induce cell death. Moreover, structural modification of natural phenolics is expected to produce analogs that may be useful tools to study the structure-activity relationships. Lastly, in various cancer types, resveratrol behaves as a chemosensitizer that lowers the threshold of cell death induction by classical anticancer agents and counteracts tumor cell chemoresistance.	[Delmas, D.] Fac Sci, INSERM, U866, UMR866, F-21000 Dijon, France; [Delmas, D.; Latruffe, N.] Univ Bourgogne, Fac Sci Gabriel, Ctr Rech Biochim Metab & Nutr LBMN, F-21000 Dijon, France; [Solary, E.] Univ Bourgogne, Fac Med, Ctr Rech Canc & Differenciat, F-21000 Dijon, France		Delmas, D (corresponding author), Fac Sci, INSERM, U866, UMR866, 6 Blvd Gabriel, F-21000 Dijon, France.	ddelmas@u-bourgogne.fr	Delmas, Dominique/AAD-9749-2019	Delmas, Dominique/0000-0003-3576-0248; Delmas, Dominique/0000-0002-8911-8499; Solary, Eric/0000-0002-8629-1341	Conseil Regional de BourgogneRegion Bourgogne-Franche-Comte; Ligue contre le Cancer, comite grand-est	We thank Dr. Dominic Batt for reading the English. This study was supported by the "Conseil Regional de Bourgogne" and the "Ligue contre le Cancer, comite grand-est".	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Med. Chem.	MAR	2011	18	8					1100	1121		10.2174/092986711795029708			22	Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy	743AS	WOS:000288988100001	21291372				2022-04-25	
J	Coutermarsh-Ott, S; Simmons, A; Capria, V; LeRoith, T; Wilson, JE; Heid, B; Philipson, CW; Qin, QZ; Hontecillas-Magarzo, R; Bassaganya-Riera, J; Ting, JPY; Dervisis, N; Allen, IC				Coutermarsh-Ott, Sheryl; Simmons, Alysha; Capria, Vittoria; LeRoith, Tanya; Wilson, Justin E.; Heid, Bettina; Philipson, Casandra W.; Qin, Qizhi; Hontecillas-Magarzo, Raquel; Bassaganya-Riera, Josep; Ting, Jenny P-Y; Dervisis, Nikolaos; Allen, Irving C.			NLRX1 suppresses tumorigenesis and attenuates histiocytic sarcoma through the negative regulation of NF-lambda B signaling	ONCOTARGET			English	Article						NLR; Nod-like receptor; urethane; cancer; inflammation	NONSMALL CELL LUNG; TUMOR-SUPPRESSOR; COLON TUMORIGENESIS; I INTERFERON; CANCER; PROTEIN; GROWTH; INFLAMMATION; ACTIVATION; PATHWAY	Histiocytic sarcoma is an uncommon malignancy in both humans and veterinary species. Research exploring the pathogenesis of this disease is scarce; thus, diagnostic and therapeutic options for patients are limited. Recent publications have suggested a role for the NLR, NLRX1, in acting as a tumor suppressor. Based on these prior findings, we hypothesized that NLRX1 would function to inhibit tumorigenesis and thus the development of histiocytic sarcoma. To test this, we utilized Nlrx1(-/-) mice and a model of urethane-induced tumorigenesis. Nlrx1(-/-) mice exposed to urethane developed splenic histiocytic sarcoma that was associated with significant up-regulation of the NF-lambda B signaling pathway. Additionally, development of these tumors was also significantly associated with the increased regulation of genes associated with AKT signaling, cell death and autophagy. Together, these data show that NLRX1 suppresses tumorigenesis and reveals new genetic pathways involved in the pathobiology of histiocytic sarcoma.	[Coutermarsh-Ott, Sheryl; Simmons, Alysha; Capria, Vittoria; LeRoith, Tanya; Heid, Bettina; Qin, Qizhi; Allen, Irving C.] Virginia Tech, VA MD Reg Coll Vet Med, Dept Biol Sci & Pathobiol, Blacksburg, VA 24061 USA; [Wilson, Justin E.; Ting, Jenny P-Y] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA; [Philipson, Casandra W.; Hontecillas-Magarzo, Raquel; Bassaganya-Riera, Josep] Virginia Tech, Virginia Bioinformat Inst, Nutr Immunol & Mol Med Lab, Blacksburg, VA USA; [Dervisis, Nikolaos] Virginia Tech, VA MD Reg Coll Vet Med, Dept Small Anim Clin Sci, Blacksburg, VA USA		Allen, IC (corresponding author), Virginia Tech, VA MD Reg Coll Vet Med, Dept Biol Sci & Pathobiol, Blacksburg, VA 24061 USA.	icallen@vt.edu	Dervisis, Nikolaos/K-8931-2016; Philipson, Casandra/AAY-5746-2021	Dervisis, Nikolaos/0000-0003-2869-1483; LeRoith, Tanya/0000-0002-1196-6949	Virginia Maryland College of Veterinary Medicine through the IRC pilot grant program; National Institute of Allergy and Infectious Diseases Animal Model Research for Veterinarians (AMRV) training grant [T32-OD010430]; OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [T32OD010430] Funding Source: NIH RePORTER	This work was supported by the Virginia Maryland College of Veterinary Medicine through the IRC pilot grant program (I.C.A.). Student work on this publication was supported by the National Institute of Allergy and Infectious Diseases Animal Model Research for Veterinarians (AMRV) training grant (T32-OD010430) (S.C.O.). We would also like to recognize the Virginia Tech Initiative for Maximizing Student Development (VT-IMSD) Program and the Virginia Tech Maximizing Academic Opportunities Program for student support throughout this project. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or any other funding agency.	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J	Badziul, D; Jakubowicz-Gil, J; Paduch, R; Glowniak, K; Gawron, A				Badziul, Dorota; Jakubowicz-Gil, Joanna; Paduch, Roman; Glowniak, Kazimierz; Gawron, Antoni			Combined treatment with quercetin and imperatorin as a potent strategy for killing HeLa and Hep-2 cells	MOLECULAR AND CELLULAR BIOCHEMISTRY			English	Article						Cancer; Cell death; Imperatorin; Quercetin	HEAT-SHOCK PROTEINS; MOLECULAR CHAPERONES; ANGELICA-DAHURICA; CANCER PREVENTION; HUMAN COLON; APOPTOSIS; DEATH; ACTIVATION; AUTOPHAGY; INDUCTION	The aim of the present study was to assess the effect of quercetin and imperatorin administered separately and in combination on apoptosis and autophagy induction in human cervical carcinoma HeLa cells and laryngeal carcinoma Hep-2 cells cultured in vitro. Conducted MTT measurements proved that quercetin and imperatorin displayed a strong antiproliferative activity manifested in markedly reduction of HeLa and Hep-2 cells viability as a result of treatment with 50 mu M of each compound. Further cell staining assays revealed that concentration mentioned above generated the highest percentage of apoptotic cells especially in the case of application of both drugs for 48 h. Simultaneous quercetin and imperatorin administration induced apoptosis remarkably stronger than treatment with single drugs. Experiments at the molecular level confirmed these results accompanied with the decreased Hsp27 and Hsp72 expression and, in addition, with increased caspases activity. Autophagy was not observed and no significant changes in the expression of beclin-1 were noticed. Additionally, experiments were performed on the above-mentioned cell lines with blocked Hsp27 and Hsp72 expression. In these cells, no significant changes in the sensitivity to apoptosis induction upon quercetin and imperatorin treatment were observed. The present study has provided evidence supporting the potential of the combination of quercetin and imperatorin drugs as a novel tool to be used in anticancer therapy. Our results have also demonstrated that blocking of the Hsp27 and Hsp72 gene expression is not enough to sensitize cancer cells to programmed cell death induction in HeLa and Hep-2 cells.	[Badziul, Dorota; Jakubowicz-Gil, Joanna; Gawron, Antoni] Marie Curie Sklodowska Univ, Dept Comparat Anat & Anthropol, Inst Biol, PL-20033 Lublin, Poland; [Paduch, Roman] Marie Curie Sklodowska Univ, Dept Virol & Immunol, Inst Microbiol & Biotechnol, PL-20033 Lublin, Poland; [Glowniak, Kazimierz] Med Univ Lublin, Dept Pharmacognosy, Med Plant Unit, PL-20093 Lublin, Poland		Badziul, D (corresponding author), Marie Curie Sklodowska Univ, Dept Comparat Anat & Anthropol, Inst Biol, Akad 19, PL-20033 Lublin, Poland.	dorota.badziul@wp.pl	Jakubowicz-Gil, Joanna/AAK-3561-2020	Jakubowicz-Gil, Joanna/0000-0003-2077-804X; Glowniak, Kazimierz/0000-0003-4333-0053; Badziul, Dorota/0000-0002-5044-0843; Paduch, Roman/0000-0001-9779-7252			Appendino G, 2004, J NAT PROD, V67, P532, DOI 10.1021/np0340652; Arya R, 2007, J BIOSCIENCES, V32, P595, DOI 10.1007/s12038-007-0059-3; Badziul D, 2014, PHARMACOL REP, V66, P292, DOI 10.1016/j.pharep.2013.10.003; BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3; Broker LE, 2005, CLIN CANCER RES, V11, P3155, DOI 10.1158/1078-0432.CCR-04-2223; Burz C, 2009, ACTA ONCOL, V48, P811, DOI 10.1080/02841860902974175; Calderwood SK, 2006, TRENDS BIOCHEM SCI, V31, P164, DOI 10.1016/j.tibs.2006.01.006; Chou CC, 2010, ARCH PHARM RES, V33, P1181, DOI 10.1007/s12272-010-0808-y; Ciocca DR, 2005, CELL STRESS CHAPERON, V10, P86, DOI 10.1379/CSC-99r.1; Egert S, 2008, J NUTR, V138, P1615, DOI 10.1093/jn/138.9.1615; Elmore S, 2007, TOXICOL PATHOL, V35, P495, DOI 10.1080/01926230701320337; Erlund I, 2004, NUTR RES, V24, P851, DOI 10.1016/j.nutres.2004.07.005; Garrido C, 2006, CELL CYCLE, V5, P2592, DOI 10.4161/cc.5.22.3448; Gibellini L, 2011, EVID-BASED COMPL ALT, V2011, P1, DOI 10.1093/ecam/neq053; Graner MW, 2007, J NEUROSCI, V27, P11214, DOI 10.1523/JNEUROSCI.3588-07.2007; Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013; Jakubowicz-Gil J, 2005, BIOCHEM PHARMACOL, V69, P1343, DOI 10.1016/j.bcp.2005.01.022; Jakubowicz-Gil J, 2014, NEUROTOX RES, V26, P64, DOI 10.1007/s12640-013-9452-x; Jakubowicz-Gil J, 2013, TUMOR BIOL, V34, P2367, DOI 10.1007/s13277-013-0785-0; Jakubowicz-Gil J, 2012, FOLIA HISTOCHEM CYTO, V50, P381, DOI [10.5603/FHC.2012.0052, 10.5603/19747]; Jakubowicz-Gil J, 2008, ACTA NEUROBIOL EXP, V68, P463; Jakubowicz-Gill J, 2008, ACTA NEUROBIOL EXP, V68, P139; Jankowska A, 1997, FOLIA HISTOCHEM CYTO, V35, P97; Jolly C, 2000, JNCI-J NATL CANCER I, V92, P1564, DOI 10.1093/jnci/92.19.1564; KASUGAI S, 1990, JPN J PHARMACOL, V52, P95, DOI 10.1254/jjp.52.95; Kim YK, 2007, PHYTOTHER RES, V21, P288, DOI 10.1002/ptr.2043; LAEMMLI UK, 1970, NATURE, V227, P680, DOI 10.1038/227680a0; LAROCCA LM, 1991, BRIT J HAEMATOL, V79, P562, DOI 10.1111/j.1365-2141.1991.tb08082.x; Lee JC, 2003, EXP CELL RES, V291, P386, DOI 10.1016/S0014-4827(03)00410-5; Lee TJ, 2006, CANCER LETT, V240, P234, DOI 10.1016/j.canlet.2005.09.013; Levine B, 2005, J CLIN INVEST, V115, P2679, DOI 10.1172/JCI26390; Liang WN, 2011, MOL MED REP, V4, P1017, DOI 10.3892/mmr.2011.533; Luo KW, 2011, CHEMOTHERAPY, V57, P449, DOI 10.1159/000331641; Luszczki JJ, 2007, EUR J PHARMACOL, V574, P133, DOI 10.1016/j.ejphar.2007.07.008; Mizushima N, 2007, GENE DEV, V21, P2861, DOI 10.1101/gad.1599207; Mosser DD, 2004, ONCOGENE, V23, P2907, DOI 10.1038/sj.onc.1207529; Murakami A, 2008, CANCER LETT, V269, P315, DOI 10.1016/j.canlet.2008.03.046; Neergheen VS, 2010, TOXICOLOGY, V278, P229, DOI 10.1016/j.tox.2009.10.010; Pandey P, 2000, ONCOGENE, V19, P1975, DOI 10.1038/sj.onc.1203531; Rahman SNSA, 2013, EVID-BASED COMPL ALT, V2013, DOI 10.1155/2013/257108; Ramos S, 2007, J NUTR BIOCHEM, V18, P427, DOI 10.1016/j.jnutbio.2006.11.004; Ravikumar B, 2010, PHYSIOL REV, V90, P1383, DOI 10.1152/physrev.00030.2009; Rocchi P, 2006, BJU INT, V98, P1082, DOI 10.1111/j.1464-410X.2006.06425.x; Sancho R, 2004, J BIOL CHEM, V279, P37349, DOI 10.1074/jbc.M401993200; Senol FS, 2011, PHYTOCHEM LETT, V4, P462, DOI 10.1016/j.phytol.2011.08.016; Sherman M, 2007, ANN NY ACAD SCI, V1113, P192, DOI 10.1196/annals.1391.030; Shi YG, 2002, MOL CELL, V9, P459, DOI 10.1016/S1097-2765(02)00482-3; Sigurdsson S, 2004, Z NATURFORSCH C, V59, P523; Singletary K, 2008, CANCER EPIDEM BIOMAR, V17, P1596, DOI 10.1158/1055-9965.EPI-07-2917; Son YO, 2004, EUR J PHARMACOL, V502, P195, DOI 10.1016/j.ejphar.2004.09.012; Stetler RA, 2010, PROG NEUROBIOL, V92, P184, DOI 10.1016/j.pneurobio.2010.05.002; Sukhramani P. 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Cell. Biochem.	JUL	2014	392	1-2					213	227		10.1007/s11010-014-2032-4			15	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	AI9EW	WOS:000337233900020	24682729	Green Published			2022-04-25	
J	Thackeray, JT; Pietzsch, S; Stapel, B; Ricke-Hoch, M; Lee, CW; Bankstahl, JP; Scherr, M; Heineke, J; Scharf, G; Haghikia, A; Bengel, FM; Hilfiker-Kleiner, D				Thackeray, James T.; Pietzsch, Stefan; Stapel, Britta; Ricke-Hoch, Melanie; Lee, Chun-Wei; Bankstahl, Jens P.; Scherr, Michaela; Heineke, Jorg; Scharf, Gesine; Haghikia, Arash; Bengel, Frank M.; Hilfiker-Kleiner, Denise			Insulin supplementation attenuates cancer-induced cardiomyopathy and slows tumor disease progression	JCI INSIGHT			English	Article							HEART-FAILURE; PERIPARTUM CARDIOMYOPATHY; THERAPEUTIC TARGET; METABOLIC SYNDROME; DIABETES-MELLITUS; SIGNAL TRANSDUCER; GLUCOSE-UPTAKE; 2 PARTS; CACHEXIA; EXPRESSION	Advanced cancer induces fundamental changes in metabolism and promotes cardiac atrophy and heart failure. We discovered systemic insulin deficiency in cachectic cancer patients. Similarly, mice with advanced B16F10 melanoma (B16F10-TM) or colon 26 carcinoma (C26-TM) displayed decreased systemic insulin associated with marked cardiac atrophy, metabolic impairment, and function. B16F10 and C26 tumors decrease systemic insulin via high glucose consumption, lowering pancreatic insulin production and producing insulin-degrading enzyme. As tumor cells consume glucose in an insulin-independent manner, they shift glucose away from cardiomyocytes. Since cardiomyocytes in both tumor models remained insulin responsive, low-dose insulin supplementation by subcutaneous implantation of insulin-releasing pellets improved cardiac glucose uptake, atrophy, and function, with no adverse side effects. In addition, by redirecting glucose to the heart in addition to other organs, the systemic insulin treatment lowered glucose usage by the tumor and thereby decreased tumor growth and volume. Insulin corrected the cancerinduced reduction in cardiac Akt activation and the subsequent overactivation of the proteasome and autophagy. Thus, cancer-induced systemic insulin depletion contributes to cardiac wasting and failure and may promote tumor growth. Low-dose insulin supplementation attenuates these processes and may be supportive in cardio-oncologic treatment concepts.	[Thackeray, James T.; Bankstahl, Jens P.; Bengel, Frank M.] Hannover Med Sch, Dept Nucl Med, Hannover, Germany; [Pietzsch, Stefan; Stapel, Britta; Ricke-Hoch, Melanie; Heineke, Jorg; Scharf, Gesine; Haghikia, Arash; Hilfiker-Kleiner, Denise] Hannover Med Sch, Dept Cardiol & Angiol, Div Mol Cardiol, Hannover, Germany; [Lee, Chun-Wei; Scherr, Michaela] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany; [Haghikia, Arash] Charite, Dept Cardiol, Campus Benjamin Franklin, Berlin, Germany		Hilfiker-Kleiner, D (corresponding author), Hannover Med Sch, Abt Kardiol & Angiol, Carl Neuberg Str 1, D-30625 Hannover, Germany.	hilfiker.denise@mh-hannover.de	Bengel, Frank/AAR-7353-2020; Haghikia, Arash/F-1348-2016; Thackeray, James/R-9350-2018	Dittrich, Gesine/0000-0002-9053-078X; Bengel, Frank/0000-0003-4529-7963	Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR); German Research Association (DFG)German Research Foundation (DFG) [HI-842/101, KFO 311]	The authors thank Martina Kasten, Silvia Gutzke, Sergej Erschow, Mirco M~ller, Birgit Brandt, ChunWei Lee, Silvia Eilert, Alexander Kanwischer, and Petra Felsch for excellent technical assistance. JTT is supported by a fellowship from the Canadian Institutes of Health Research. This work was supported by the German Research Association (DFG) (HI-842/10-1, KFO311, Rebirth II).	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J	Zhang, JW; Zhang, SS; Song, JR; Sun, K; Zong, C; Zhao, QD; Liu, WT; Li, R; Wu, MC; Wei, LX				Zhang, Jian-wei; Zhang, Shan-shan; Song, Jian-rui; Sun, Kai; Zong, Chen; Zhao, Qiu-dong; Liu, Wen-ting; Li, Rong; Wu, Meng-chao; Wei, Li-xin			Autophagy inhibition switches low-dose camptothecin-induced premature senescence to apoptosis in human colorectal cancer cells	BIOCHEMICAL PHARMACOLOGY			English	Article						Human colorectal cancer cells; Low-dose chemotherapy; DNA damage response; Autophagy; Senescence; Apoptosis	DOUBLE-STRAND BREAKS; TUMOR-CELLS; DNA-DAMAGE; CELLULAR SENESCENCE; IN-VITRO; CHEMOTHERAPY; P53; CHECKPOINT; DATABASE; THERAPY	Recently, several studies indicated that senescent tumor cells are resistant to apoptosis in chemotherapy. They may return to cell cycle, thus act as stumbling blocks in anticancer treatments. In the present study, we found that, in human colorectal cancer cells, low-dose camptothecin (CPT) simultaneously induced autophagy and premature senescence through AMPK-TSC2-mTOR pathway and ATM-Chk2-p53-p21 pathway respectively. What's important is the suppression of autophagy substantially increased apoptosis and greatly attenuated senescence possibly by blocking p53/p21 pathway, which suggests that autophagy plays an indispensable role in sustaining cell senescence caused by low-dose CPT. The combination of low-dose CPT and autophagy inhibitor, a way to lead senescent cells to die, would be potentially valuable in cancer therapy. (C) 2014 Elsevier Inc. All rights reserved.	[Zhang, Jian-wei; Zhang, Shan-shan; Song, Jian-rui; Sun, Kai; Zong, Chen; Zhao, Qiu-dong; Liu, Wen-ting; Li, Rong; Wu, Meng-chao; Wei, Li-xin] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Tumor Immunol & Gene Therapy Ctr, Shanghai 200438, Peoples R China; [Song, Jian-rui] Univ Michigan, Dept Cell Biol, Ann Arbor, MI 48109 USA; [Song, Jian-rui] Univ Michigan, Dept Dev Biol, Ann Arbor, MI 48109 USA; [Sun, Kai] Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Med Sci Res Ctr, Shanghai 200030, Peoples R China		Wei, LX (corresponding author), Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Tumor Immunol & Gene Therapy Ctr, 225 Changhai Rd, Shanghai 200438, Peoples R China.	weilixin_smmu@163.com			Key Basic Research Project of China [2012CBA01303, 2011CB966200, 2010CB945600, 2011CB965100]; Key project of National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81030041]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31171321, 81101622, 81372330]; Special Funds for National key Sci-Tech Sepcial Project of China [2012ZX10002-016, 2012ZX10002011-011]; Shanghai Science and Technology CommitteeShanghai Science & Technology Committee [10ZR1439600, 11ZR1449500]; Shanghai Municipal Health Bureau [20114004]; Science Fund for Creative Research Groups, National Natural Science Foundation of China (NSFC), China [81221061]	This project was supported by Key Basic Research Project of China (Grant NO.2012CBA01303, 2011CB966200, 2010CB945600, 2011CB965100); Key project of National Natural Science Foundation of China (Grant NO. 81030041); National Natural Science Foundation of China (Grant NO. 31171321, 81101622, 81372330); Special Funds for National key Sci-Tech Sepcial Project of China (Grant NO. 2012ZX10002-016, 2012ZX10002011-011); Shanghai Science and Technology Committee (Grant NO. 10ZR1439600, 11ZR1449500); Shanghai Municipal Health Bureau (Grant NO.20114004) and Science Fund for Creative Research Groups, National Natural Science Foundation of China (NSFC), China (Grant NO. 81221061).	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Pharmacol.	AUG 1	2014	90	3					265	275		10.1016/j.bcp.2014.05.009			11	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	AL6FV	WOS:000339228900008	24858802				2022-04-25	
J	Masuelli, L; Di Stefano, E; Fantini, M; Mattera, R; Benvenuto, M; Marzocchella, L; Sacchetti, P; Focaccetti, C; Bernardini, R; Tresoldi, I; Izzi, V; Mattei, M; Frajese, GV; Lista, F; Modesti, A; Bei, R				Masuelli, Laura; Di Stefano, Enrica; Fantini, Massimo; Mattera, Rosanna; Benvenuto, Monica; Marzocchella, Laura; Sacchetti, Pamela; Focaccetti, Chiara; Bernardini, Roberta; Tresoldi, Ilaria; Izzi, Valerio; Mattei, Maurizio; Frajese, Giovanni Vanni; Lista, Florigio; Modesti, Andrea; Bei, Roberto			Resveratrol potentiates the in vitro and in vivo anti-tumoral effects of curcumin in head and neck carcinomas	ONCOTARGET			English	Article						polyphenols; head and neck cancer; curcumin; resveratrol	SQUAMOUS-CELL CARCINOMA; FACTOR-KAPPA-B; MULTIPLE ERBB RECEPTORS; ORAL-CANCER CELLS; BCL-X-L; DIETARY POLYPHENOLS; INDUCED AUTOPHAGY; DOWN-REGULATION; CLINICAL-TRIAL; COLON-CANCER	The survival rate of head and neck squamous cell carcinomas (HNSCC) patients has not considerably changed over the last two decades. Polyphenols inhibit the growth of cancer cells. We determined whether the combination of Resveratrol (RES) and Curcumin (CUR) enhanced their in vitro and in vivo antitumor activities on HNSCC cell lines compared to the single compounds. We provide evidence that RES potentiated the apoptotic effect and reduced the IC50 of CUR on HNSCC cell lines. The model of compounds interaction indicated the onset of an additive effect of the two compounds compared to the single treatment after decrease of their concentrations. RES+CUR compared to CUR increased the PARP-1 cleavage, the Bax/Bcl-2 ratio, the inhibition of ERK1 and ERK2 phosphorylation, and the expression of LC3 II simultaneously with the formation of autophagic vacuoles. RES and CUR induced cytoplasmic NF-kappa B accumulation. RES+CUR administrations were safe in BALB/c mice and reduced the growth of transplanted salivary gland cancer cells (SALTO) more efficiently than CUR. Overall, combinations of CUR and RES was more effective in inhibiting in vivo and in vitro cancer growth than the treatment with CUR. Additional studies will be needed to define the therapeutic potential of these compounds in combination.	[Masuelli, Laura; Di Stefano, Enrica; Mattera, Rosanna; Sacchetti, Pamela] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy; [Fantini, Massimo; Benvenuto, Monica; Marzocchella, Laura; Tresoldi, Ilaria; Izzi, Valerio; Modesti, Andrea; Bei, Roberto] Univ Roma Tor Vergata, Dept Clin Sci & Translat Med, Rome, Italy; [Focaccetti, Chiara; Bernardini, Roberta; Mattei, Maurizio] Univ Roma Tor Vergata, STA, Rome, Italy; [Frajese, Giovanni Vanni] Univ Roma, Dipartimento Sci Motorie Umane & Salute, Foro Italico, Italy; [Lista, Florigio] Ctr Studi & Ric Sanita & Vet Esercito, Rome, Italy		Bei, R (corresponding author), Univ Roma La Sapienza, Dept Expt Med, Piazzale Aldo Moro 5, I-00185 Rome, Italy.	bei@med.uniroma2.it	Bei, Roberto/W-8023-2019; Bernardini, Roberta/AAC-1301-2019; Masuelli, Laura/AGW-4259-2022; Benvenuto, Monica/K-2685-2016; Focaccetti, Chiara/AAD-9378-2019; Izzi, Valerio/Q-5720-2019; Mattei, Maurizio/AAC-1303-2019	Bernardini, Roberta/0000-0002-1675-0645; Benvenuto, Monica/0000-0002-2520-1306; Focaccetti, Chiara/0000-0002-7334-3966; Izzi, Valerio/0000-0002-9960-4917; Mattei, Maurizio/0000-0002-0814-8873; MASUELLI, Laura/0000-0001-8174-8034; Fantini, Massimo/0000-0002-8164-2587	PRIN, Ricerca Universitaria "Sapienza"	This study was supported by a grant from PRIN (R.B.), Ricerca Universitaria "Sapienza" 2012 (L.M.). The authors wish to thank Barbara Bulgarini for help in manuscript preparation. SALTO cells were kindly provided by Prof. Federica Cavallo (University of Turin) and Prof. Patrizia Nanni (University of Bologna).	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Shureiqi I, 2011, CANCER PREV RES, V4, P296, DOI 10.1158/1940-6207.CAPR-11-0060; Tsao R, 2010, NUTRIENTS, V2, P1231, DOI 10.3390/nu2121231; Tsvetkov P, 2005, P NATL ACAD SCI USA, V102, P5535, DOI 10.1073/pnas.0501828102; Vander Broek R, 2011, ORAL ONCOL, p[00714, S1368]; Walle T, 2004, DRUG METAB DISPOS, V32, P1377, DOI 10.1124/dmd.104.000885; Woo JH, 2003, CARCINOGENESIS, V24, P1199, DOI 10.1093/carcin/bgg082; Zlotogorski A, 2013, ORAL ONCOL, V49, P502, DOI 10.1016/j.oraloncology.2013.02.011	66	72	76	1	10	IMPACT JOURNALS LLC	ORCHARD PARK	6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA		1949-2553		ONCOTARGET	Oncotarget	NOV 15	2014	5	21					10745	10762		10.18632/oncotarget.2534			18	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	AZ2AL	WOS:000348036900041	25296980	Green Published, gold, Green Submitted			2022-04-25	
J	Ha, YJ; Kim, CW; Roh, SA; Cho, DH; Park, JL; Kim, SY; Kim, JH; Choi, EK; Kim, YS; Kim, JC				Ha, Ye J.; Kim, Chan W.; Roh, Seon A.; Cho, Dong H.; Park, Jong L.; Kim, Seon Y.; Kim, Jong H.; Choi, Eun K.; Kim, Yong S.; Kim, Jin C.			Epigenetic Regulation of KLHL34 Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients	INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS			English	Article							SEXUAL FUNCTION; RADIOTHERAPY; INHIBITION; AUTOPHAGY	Purpose: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). Methods and Materials: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC. In the second step, the methylation status of selected sites was analyzed by pyrosequencing in 67 LARC patients, including 24 patients analyzed in the first step. Finally, colorectal cancer cell clones with stable KLHL34 knockdown were generated and tested for cellular sensitivity to radiation. Results: Genome-wide screening identified 7 hypermethylated CpG sites (DZIP1 cg24107021, DZIP1 cg26886381, ZEB1 cg04430381, DKK3 cg041006961, STL cg00991794, KLHL34 cg01828474, and ARHGAP6 cg07828380) associated with preoperative CRT responses. Radiosensitivity in patients with hypermethylated KLHL34 cg14232291 was confirmed by pyrosequencing in additional cohorts. Knockdown of KLHL34 significantly reduced colony formation (KLHL34 sh#1: 20.1%, P = .0001 and KLHL34 sh#2: 15.8%, P = .0002), increased the cytotoxicity (KLHL34 sh#1: 14.8%, P = .019 and KLHL34 sh#2: 17.9%, P = .007) in LoVo cells, and increased radiation-induced caspase-3 activity and the sub-G1 population of cells. Conclusions: The methylation status of KLHL34 cg14232291 may be a predictive candidate of sensitivity to preoperative CRT, although further validation is needed in large cohorts using various cell types. (C) 2015 Elsevier Inc.	[Ha, Ye J.; Kim, Chan W.; Roh, Seon A.; Kim, Jin C.] Univ Ulsan, Coll Med, Dept Surg, Seoul 138736, South Korea; [Kim, Jong H.; Choi, Eun K.] Univ Ulsan, Dept Radiat Oncol, Seoul 138736, South Korea; [Ha, Ye J.; Roh, Seon A.; Cho, Dong H.; Choi, Eun K.; Kim, Yong S.; Kim, Jin C.] Asan Med Ctr, Asan Inst Life Sci, Seoul, South Korea; [Ha, Ye J.; Roh, Seon A.; Cho, Dong H.; Choi, Eun K.; Kim, Yong S.; Kim, Jin C.] Asan Med Ctr, Inst Innovat Canc Res, Seoul, South Korea; [Cho, Dong H.] Kyung Hee Univ, Grad Sch East West Med Sci, Seoul, South Korea; [Park, Jong L.; Kim, Seon Y.; Kim, Yong S.] Med Genom Res Ctr, Korea Res Inst Bioscience & Biotechnol, Daejeon, South Korea		Kim, JC (corresponding author), Univ Ulsan, Coll Med, Dept Surg, 88 Olymp Ro 43 Gil, Seoul 138736, South Korea.	yongsung@kribb.re.kr; jckim@amc.seoul.kr			Asan Institute for Life Sciences [2014-69]; National Research Foundation [NRF-2013R1A2A1A03070986]; Ministry of Science, ICT and Future Planning, the Korea Health 21 RD Project [HI06C0868, HI13C1750]; Center for Development and Commercialization of Anti-Cancer Therapeutics, Ministry of Health and Welfare, Republic of Korea [HI10C2014]	Supported by grants (to J.C. Kim) from the Asan Institute for Life Sciences (2014-69), the National Research Foundation (NRF-2013R1A2A1A03070986), Ministry of Science, ICT and Future Planning, the Korea Health 21 R&D Project (HI06C0868 and HI13C1750), and the Center for Development and Commercialization of Anti-Cancer Therapeutics (HI10C2014), Ministry of Health and Welfare, Republic of Korea.	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J. Radiat. Oncol. Biol. Phys.	MAR 1	2015	91	3					650	658		10.1016/j.ijrobp.2014.11.013			9	Oncology; Radiology, Nuclear Medicine & Medical Imaging	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Radiology, Nuclear Medicine & Medical Imaging	CA8YJ	WOS:000349206600025	25680604				2022-04-25	
J	Poluzzi, C; Casulli, J; Goyal, A; Mercer, TJ; Neill, T; Iozzo, RV				Poluzzi, Chiara; Casulli, Joshua; Goyal, Atul; Mercer, Thomas J.; Neill, Thomas; Iozzo, Renato V.			Endorepellin Evokes Autophagy in Endothelial Cells	JOURNAL OF BIOLOGICAL CHEMISTRY			English	Article							HEPARAN-SULFATE PROTEOGLYCAN; FIBROBLAST-GROWTH-FACTOR; PERLECAN PROTEIN CORE; BASEMENT-MEMBRANE PROTEOGLYCANS; DENSITY-LIPOPROTEIN-RECEPTOR; COLON CARCINOMA-CELLS; IMPRINTED GENE; CANCER GROWTH; TUMOR-GROWTH; ALPHA(2)BETA(1) INTEGRINS	Endorepellin, the C-terminal fragment of the heparan sulfate proteoglycan perlecan, possesses angiostatic activity via dual receptor antagonism, through concurrent binding to the alpha 2 beta 1 integrin and vascular endothelial growth factor receptor 2 (VEGFR2). Here, we discovered that soluble endorepellin induced autophagy in endothelial cells by modulating the expression of Beclin 1, LC3, and p62, three established autophagic markers. Moreover, endorepellin evoked expression of the imprinted tumor suppressor gene Peg3 and its co-localization with Beclin 1 and LC3 in autophagosomes, suggesting a major role for this gene in endothelial cell autophagy. Mechanistically, endorepellin induced autophagy by down-regulating VEGFR2 via the two LG1/2 domains, whereas the C-terminal LG3 domain, the portion responsible for binding the alpha 2 beta 1 integrin, was ineffective. Endorepellin also induced transcriptional activity of the BECN1 promoter in endothelial cells, and the VEGFR2-specific tyrosine kinase inhibitor, SU5416, blocked this effect. Finally, we found a correlation between endorepellin-evoked inhibition of capillary morphogenesis and enhanced autophagy. Thus, we have identified a new role for this endogenous angiostatic fragment in inducing autophagy through a VEGFR2-dependent but alpha 2 beta 1 integrin-independent pathway. This novel mechanism specifically targets endothelial cells and could represent a promising new strategy to potentiate the angiostatic effect of endorepellin and perhaps other angiostatic matrix proteins.	[Iozzo, Renato V.] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA; Thomas Jefferson Univ, Canc Cell Biol & Signaling Program, Kimmel Canc Ctr, Philadelphia, PA 19107 USA		Iozzo, RV (corresponding author), Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, 1020 Locust St,Ste 336 JAH, Philadelphia, PA 19107 USA.	renato.iozzo@jefferson.edu	Poluzzi, Chiara/T-3376-2019; Iozzo, Renato/AAS-1980-2020	Casulli, Joshua/0000-0002-3733-7614; Iozzo, Renato/0000-0002-5908-5112	National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [RO1 CA3948, RO1 CA47282, RO1 CA164462, T32 AA07463]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA039481, R01CA047282, R01CA164462, P30CA056036] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISMUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [T32AA007463] Funding Source: NIH RePORTER	This work was supported, in whole or in part, by National Institutes of Health Grants RO1 CA3948, RO1 CA47282, and RO1 CA164462 (to R. V. I.).; Supported by National Institutes of Health Training Grant T32 AA07463.	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Biol. Chem.	JUN 6	2014	289	23					16114	16128		10.1074/jbc.M114.556530			15	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	AJ8ON	WOS:000337965700019	24737315	Green Published, hybrid			2022-04-25	
J	Liu, ML; Zhang, Q; Yuan, X; Jin, L; Wang, LL; Fang, TT; Wang, WB				Liu, Mu-Lin; Zhang, Qiao; Yuan, Xiao; Jin, Long; Wang, Li-Li; Fang, Tao-Tao; Wang, Wen-Bin			Long noncoding RNA RP4 functions as a competing endogenous RNA through miR-7-5p sponge activity in colorectal cancer	WORLD JOURNAL OF GASTROENTEROLOGY			English	Article						Colorectal cancer; long noncoding RNA RP4; SH3GLB1; miR-7-5p; competing endogenous RNA	MYC-DRIVEN LYMPHOMAGENESIS; CELL-PROLIFERATION; APOPTOSIS; PROGRESSION; MITOPHAGY; AUTOPHAGY	AIM To investigate the role of long noncoding RNA (lncRNA) RP4 in colorectal cancer. METHODS Lentivirus-mediated lncRNA RP4 overexpression and knockdown were performed in the colorectal cancer cell line SW480. Cell proliferation, tumor growth, and early apoptosis were evaluated by a cell counting kit-8 assay, an in vivo xenograft tumor model, and annexin V/propidium iodide staining, respectively. Analysis of the lncRNA RP4 mechanism involved assessment of the association of its expression with miR-7-5p and the SH3GLB1 gene. Western blot analysis was also performed to assess the effect of lncRNA RP4 on the autophagy-mediated cell death pathway and phosphatidylinositol-3-kinase (PI3K)/Akt signaling. RESULTS Cell proliferation, tumor growth, and early apoptosis in SW480 cells were negatively regulated by lncRNA RP4. Functional experiments indicated that lncRNA RP4 directly upregulated SH3GLB1 expression by acting as a competing endogenous RNA (ceRNA) for miR-7-5p. This interaction led to activation of the autophagy-mediated cell death pathway and de-repression of PI3K and Akt phosphorylation in colorectal cancer cells in vivo. CONCLUSION Our results demonstrated that lncRNA RP4 is a ceRNA that plays an important role in the pathogenesis of colorectal cancer, and could be a potential therapeutic target for colorectal cancer treatment.	[Liu, Mu-Lin; Jin, Long; Wang, Li-Li; Fang, Tao-Tao] Bengbu Med Coll, Affiliated Hosp 1, Dept Gastrointestinal Surg, Bengbu 233004, Anhui, Peoples R China; [Zhang, Qiao] Xinxiang Med Univ, Affiliated Hosp 1, Dept Gen Surg, Xinxiang 453100, Henan, Peoples R China; [Yuan, Xiao; Wang, Wen-Bin] Anhui Med Univ, Affiliated Hosp 4, Dept Gen Surg, 372 Tunxi Rd, Hefei 230022, Anhui, Peoples R China		Wang, WB (corresponding author), Anhui Med Univ, Affiliated Hosp 4, Dept Gen Surg, 372 Tunxi Rd, Hefei 230022, Anhui, Peoples R China.	surdoctor@163.com			Scientific Research Foundation of Anhui Education Department [KJ2017A219]; Scientific Research Foundation of Academic Leader of Anhui Province [2016H105]; education talent Foundation of universities of Anhui Education Department [gxbjZD2016070]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81500373]; Natural Science Foundation of Anhui ProvinceNatural Science Foundation of Anhui Province [1608085MH193]	Supported by Scientific Research Foundation of Anhui Education Department, No. KJ2017A219 to Liu ML; Scientific Research Foundation of Academic Leader of Anhui Province, No. 2016H105 to Liu ML; education talent Foundation of universities of Anhui Education Department, No. gxbjZD2016070 to Liu ML; National Natural Science Foundation of China, No. 81500373 to Wang WB; and Natural Science Foundation of Anhui Province, No. 1608085MH193 to Wang WB.	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Gastroenterol.	MAR 7	2018	24	9					1004	1012		10.3748/wjg.v24.i9.1004			9	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	FY3BM	WOS:000426692100005	29531464	Green Published, hybrid, Green Submitted			2022-04-25	
J	Tsai, HY; Ho, CT; Chen, YK				Tsai, Hui-Yun; Ho, Chi-Tang; Chen, Yu-Kuo			Biological actions and molecular effects of resveratrol, pterostilbene, and 3 '-hydroxypterostilbene	JOURNAL OF FOOD AND DRUG ANALYSIS			English	Review						3 '-hydroxypterostilbene; bioavailability; biological actions; pterostilbene; resveratrol; stilbenes	IMPROVES GLYCEMIC CONTROL; ACTIVATED PROTEIN-KINASE; CELL-CYCLE ARREST; COLON CARCINOGENESIS; CALORIC RESTRICTION; GENE-EXPRESSION; DOWN-REGULATION; CANCER CELLS; LIFE-SPAN; APOPTOSIS	Stilbenes are a class of polyphenolic compounds, naturally found in a wide variety of dietary sources such as grapes, berries, peanuts, red wine, and some medicinal plants. There are several well-known stilbenes including trans-resveratrol, pterostilbene, and 3'-hydroxypterostilbene. The core chemical structure of stilbene compounds is 1,2-diphenylethylene. Recently, stilbenes have attracted extensive attention and interest due to their wide range of health-beneficial effects such as anti-inflammation, -carcinogenic, -diabetes, and -dyslipidemia activities. Moreover, accumulating in vitro and in vivo studies have reported that stilbene compounds act as inducers of multiple cell-death pathways such as apoptosis, cell cycle arrest, and autophagy for chemopreventive and chemotherapeutic agents in several types of cancer cells. The aim of this review is to highlight recent molecular findings and biological actions of trans-resveratrol, pterostilbene, and 3'-hydroxypterostilbene. Copyright (C) 2016, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC.	[Tsai, Hui-Yun; Ho, Chi-Tang] Rutgers State Univ, Dept Food Sci, 65 Dudley Rd, New Brunswick, NJ 08901 USA; [Chen, Yu-Kuo] Natl Pingtung Univ Sci & Technol, Dept Food Sci, 1 Shuefu Rd, Pingtung 91201, Taiwan		Ho, CT (corresponding author), Rutgers State Univ, Dept Food Sci, 65 Dudley Rd, New Brunswick, NJ 08901 USA.; Chen, YK (corresponding author), Natl Pingtung Univ Sci & Technol, Dept Food Sci, 1 Shuefu Rd, Pingtung 91201, Taiwan.	ho@aesop.rutgers.edu; chenyk@mail.npust.edu.tw		Chen, Yu-Kuo/0000-0002-8031-8312			Azzolini M, 2014, MOL NUTR FOOD RES, V58, P2122, DOI 10.1002/mnfr.201400244; Bagul PK, 2015, BIOCHEM BIOPH RES CO, V468, P221, DOI 10.1016/j.bbrc.2015.10.126; Baur JA, 2006, NATURE, V444, P337, DOI 10.1038/nature05354; Bhakkiyalakshmi E, 2014, BRIT J PHARMACOL, V171, P1747, DOI 10.1111/bph.12577; Bhatt JK, 2012, NUTR RES, V32, P537, DOI 10.1016/j.nutres.2012.06.003; Chakraborty A, 2012, MOL CELL ENDOCRINOL, V355, P25, DOI 10.1016/j.mce.2012.01.009; Chakraborty A, 2010, TOXICOL IN VITRO, V24, P1215, DOI 10.1016/j.tiv.2010.02.007; 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Food Drug Anal.	JAN	2017	25	1					134	147		10.1016/j.jfda.2016.07.004			14	Food Science & Technology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Food Science & Technology; Pharmacology & Pharmacy	EJ4IM	WOS:000393180200015	28911531	gold	Y	N	2022-04-25	
J	Fu, YY; Gu, QQ; Luo, L; Xu, JC; Luo, YP; Xia, F; Han, FH; Hong, L; Yin, XM; Huang, ZY; Li, M				Fu, Yuanyuan; Gu, Qianqian; Luo, Li; Xu, Jiecheng; Luo, Yuping; Xia, Fan; Han, Fanghai; Hong, Liang; Yin, Xiao-Ming; Huang, Zhiying; Li, Min			New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function	CANCERS			English	Article						ATG4B; autophagy; colorectal cancer; dual-function inhibitor; lysosome inhibition; new anti-cancer strategy	AUTOPHAGY; CELLS; CHLOROQUINE; DISCOVERY; PROTEIN; TARGET; POTENT	Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy. Although some inhibitors of either lysosome or ATG4B were reported, there are limitations in the use of these single target compounds. Considering multi-functional drugs have advantages, such as high efficacy and low toxicity, we first screened and validated a batch of compounds designed and synthesized in our laboratory by combining the screening method of ATG4B inhibitors and the identification method of lysosome inhibitors. ATG4B activity was effectively inhibited in vitro. Moreover, 163N inhibited autophagic flux and caused the accumulation of autolysosomes. Further studies demonstrated that 163N could not affect the autophagosome-lysosome fusion but could cause lysosome dysfunction. In addition, 163N diminished tumor cell viability and impaired the development of colorectal cancer in vivo. The current study findings indicate that the dual effect inhibitor 163N offers an attractive new anti-cancer drug and compounds having a combination of lysosome inhibition and ATG4B inhibition are a promising therapeutic strategy for colorectal cancer therapy.	[Fu, Yuanyuan; Gu, Qianqian; Luo, Li; Xu, Jiecheng; Luo, Yuping; Xia, Fan; Hong, Liang; Huang, Zhiying; Li, Min] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China; [Han, Fanghai] Sun Yat Sen Univ, Dept Gastrointestinal Surg, Guangzhou 510120, Peoples R China; [Yin, Xiao-Ming] Tulane Univ, Sch Med, Dept Pathol & Lab Med, 1430 Tulane Ave, New Orleans, LA 70112 USA		Huang, ZY; Li, M (corresponding author), Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China.	fuyy6@mail2.sysu.edu.cn; guqq@mail2.sysu.edu.cn; luoli26@mail2.sysu.edu.cn; xujch6@mail2.sysu.edu.cn; luoyp26@mail2.sysu.edu.cn; xiaf6@mail2.sysu.edu.cn; fh_han@163.com; hongliang@mail.sysu.edu.cn; xmyin@tulane.edu; hzhiying@mail.sysu.edu.cn; limin65@mail.sysu.edu.cn		li, min/0000-0002-5657-8675	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31970699, 31671437, 81773992, 81572925]; Guangdong Basic and Applied Basic Research Foundation [2019A1515011030]	This work was supported by the National Natural Science Foundation of China (31970699, 31671437, 81773992, 81572925) and the Guangdong Basic and Applied Basic Research Foundation (2019A1515011030).	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J	Yamada, T; Ashida, Y; Tatebayashi, D; Abe, M; Himori, K				Yamada, Takashi; Ashida, Yuki; Tatebayashi, Daisuke; Abe, Masami; Himori, Koichi			Cancer Cachexia Induces Preferential Skeletal Muscle Myosin Loss When Combined With Denervation	FRONTIERS IN PHYSIOLOGY			English	Article						cancer cachexia; denervation; muscle atrophy; catabolism; anabolism	HEAVY-CHAIN; WEIGHT-LOSS; ATROPHY; ACTIVATION; EXPRESSION; AUTOPHAGY; CHEMOTHERAPY; DEGRADATION; PATHWAYS; MODEL	Patients with cancer cachexia (CCX) suffer from muscle wasting, which is often but not always accompanied by selective loss of myosin. Here we examined the effects of CCX on muscle mass and myosin heavy chain (MyHC) expression in denervated (DEN) muscles, especially focusing on the protein synthesis and degradation pathways. Male CD2F1 mice were randomly divided into control (CNT) and CCX groups and their left sciatic nerve was transected. CCX was induced by an intraperitoneal injection of colon 26 cells. After 14 days, the serum concentration of IL-6 and corticosteroid was higher in CCX mice than in CNT mice. The combination of CCX with DEN (CCX + DEN) resulted in a marked reduction of the gastrocnemius muscle weight (-69%) that was significantly lower than DEN (-53%) or CCX (-36%) alone. CCX had no effect on MyHC content, but it elicited a preferential MyHC loss when combined with DEN. The expression levels of autophagy markers cathepsin D and LC3BII/I ratio were markedly higher in the CCX + DEN group than in the CNT + DEN and the CCX groups. Paradoxically, there was an increase in protein synthesis rate and phosphorylation levels of p70S6K and rpS6, markers of mTORC1 signaling, in the CNT + DEN group, and these molecular alterations were inhibited in the CCX + DEN group. Our data indicate that CCX aggravates muscle atrophy in DEN muscles by inducing seletive loss of myosin, which involves inactivity dependent mechanisms that is likely to be a consequence of increased autophagy-mediated protein breakdown coupled with impaired protein synthesis.	[Yamada, Takashi; Ashida, Yuki; Tatebayashi, Daisuke; Abe, Masami; Himori, Koichi] Sapporo Med Univ, Grad Sch Hlth Sci, Sapporo, Hokkaido, Japan		Yamada, T (corresponding author), Sapporo Med Univ, Grad Sch Hlth Sci, Sapporo, Hokkaido, Japan.	takashi.yamada1976@sapmed.ac.jp	Yamada, Takashi/AAZ-6212-2021; Yamada, Takashi/U-8443-2019	Yamada, Takashi/0000-0003-1797-3880; Yamada, Takashi/0000-0003-1797-3880	Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [JP15K12585]	This work was supported by grants fromthe Japan Society for the Promotion of Science (No. JP15K12585 to TY).	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Physiol.	APR 28	2020	11								445	10.3389/fphys.2020.00445			9	Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Physiology	LO1HC	WOS:000533378200001	32425814	gold, Green Published			2022-04-25	
J	Iwata, Y; Suzuki, N; Ohtake, H; Kamauchi, S; Hashimoto, N; Kiyono, T; Wakabayashi, S				Iwata, Yuko; Suzuki, Nobuyuki; Ohtake, Hitomi; Kamauchi, Shinya; Hashimoto, Naohiro; Kiyono, Tohru; Wakabayashi, Shigeo			Cancer cachexia causes skeletal muscle damage via transient receptor potential vanilloid 2-independent mechanisms, unlike muscular dystrophy	JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE			English	Article						TRPV2; transient receptor potential vanilloid type 2; DGC; dystrophin glycoprotein complex; Cancer cachexia; Muscular dystrophy; LLC; Lewis lung carcinoma	ACTIVATION; CELLS; CA2+; PATHOPHYSIOLOGY; DEGENERATION; CONTRIBUTES; AUTOPHAGY; MYOTUBES; CHANNELS; PATHWAY	BackgroundMuscle wasting during cancer cachexia contributes to patient morbidity. Cachexia-induced muscle damage may be understood by comparing its symptoms with those of other skeletal muscle diseases, but currently available data are limited. MethodsWe modelled cancer cachexia in mice bearing Lewis lung carcinoma/colon adenocarcinoma and compared the associated muscle damage with that in a murine muscular dystrophy model (mdx mice). We measured biochemical and immunochemical parameters: amounts/localization of cytoskeletal proteins and/or Ca2+ signalling proteins related to muscle function and abnormality. We analysed intracellular Ca2+ mobilization and compared results between the two models. Involvement of Ca2+-permeable channel transient receptor potential vanilloid 2 (TRPV2) was examined by inoculating Lewis lung carcinoma cells into transgenic mice expressing dominant-negative TRPV2. ResultsTumourigenesis caused loss of body and skeletal muscle weight and reduced muscle force and locomotor activity. Similar to mdx mice, cachexia muscles exhibited myolysis, reduced sarcolemmal sialic acid content, and enhanced lysosomal exocytosis and sarcolemmal localization of phosphorylated Ca2+/CaMKII. Abnormal autophagy and degradation of dystrophin also occurred. Unlike mdx muscles, cachexia muscles did not exhibit regeneration markers (centrally nucleated fibres), and levels of autophagic proteolytic pathway markers increased. While a slight accumulation of TRPV2 was observed in cachexia muscles, Ca2+ influx via TRPV2 was not elevated in cachexia-associated myotubes, and the course of cachexia pathology was not ameliorated by dominant-negative inhibition of TRPV2. ConclusionsThus, cancer cachexia may induce muscle damage through TRPV2-independent mechanisms distinct from those in muscular dystrophy; this may help treat patients with tumour-induced muscle wasting.	[Iwata, Yuko; Ohtake, Hitomi; Kamauchi, Shinya; Wakabayashi, Shigeo] Natl Cerebral & Cardiovasc Ctr, Res Inst, Dept Mol Physiol, Suita, Osaka 5658565, Japan; [Suzuki, Nobuyuki] Kyowa Hakko Kirin CO Ltd, Chiyoda Ku, Tokyo, Japan; [Hashimoto, Naohiro] Natl Ctr Geriatr & Gerontol, Natl Inst Longev Sci, Dept Regenerat Med, Oobu, Aichi 4748522, Japan; [Kiyono, Tohru] Natl Canc Ctr, Viol Div, Chuo Ku, Tokyo 1040045, Japan		Iwata, Y (corresponding author), Natl Cerebral & Cardiovasc Ctr, Res Inst, Dept Mol Physiol, Suita, Osaka 5658565, Japan.	yukoiwat@ri.ncvc.go.jp			Japanese Ministry of Education, Culture, Sports, Science and TechnologyMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [18077015, 19390080, 17659241, 18590796, 20590874]; National Institute of Biomedical InnovationNational Institute of Biomedical Innovation; Japanese Ministry of Health, Labour and WelfareMinistry of Health, Labour and Welfare, Japan [17A-1, 16B-2, 19A-7, 22-5]	This work was supported by a grant-in-aid for Priority Areas 18077015 (to S.W.); Grants-in-Aid 19390080, 17659241 (to S.W.), 18590796, and 20590874 (to Y.I.); a grant for the Cooperative Link for Unique Science and Technology for Economy Revitalization (to S. W.) from the Japanese Ministry of Education, Culture, Sports, Science and Technology; a grant for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation; and research grants for Cardiovascular Diseases (17A-1; to S. W.) and Nervous and Mental Disorders (16B-2, 19A-7, and 22-5; to Y.I.) from the Japanese Ministry of Health, Labour and Welfare.	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Cachexia Sarcopenia Muscle	JUN	2016	7	3					366	376		10.1002/jcsm.12067			11	Geriatrics & Gerontology; Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	Geriatrics & Gerontology; General & Internal Medicine	DR4JR	WOS:000379868200013	27239414	Green Published, gold			2022-04-25	
J	Bravo-San Pedro, JM; Wei, YJ; Sica, V; Maiuri, MC; Zou, ZJ; Kroemer, G; Levine, B				Bravo-San Pedro, Jose Manuel; Wei, Yongjie; Sica, Valentina; Maiuri, Maria Chiara; Zou, Zhongju; Kroemer, Guido; Levine, Beth			BAX and BAK1 are dispensable for ABT-737-induced dissociation of the BCL2-BECN1 complex and autophagy	AUTOPHAGY			English	Article						ABT-737; apoptosis; autophagy; BAX; BAK1; BCL2; BECN1 (Beclin 1); ACTB; actin; Baf A1; bafilomycin A(1); BAK1; BCL2-antagonist; killer 1; BAX; BCL2-associated X protein; BCL2; B-cell CLL; lymphoma 2; BECN1; Beclin 1; autophagy-related; DKO; double-knockout; FBS; fetal bovine serum; GAPDH; glyceraldehyde-3-phosphate dehydrogenase; HBSS; Hanks' balanced salt solution; HRP; horseradish peroxidase; MAP1LC3; LC3; microtubule-associated protein 1 light chain 3; MCL1; myeloid cell leukemia 1; MEFs; mouse embryonic fibroblasts; MTOR; mechanistic target of rapamycin; PBS; phosphate-buffered saline; SQSTM1; sequestosome 1; STS; staurosporine; WT; wild type	BCL-2 FAMILY-MEMBERS; BECLIN 1-DEPENDENT AUTOPHAGY; 1 PHOSPHORYLATION; BH3-ONLY PROTEIN; MOLECULAR-BASIS; BH3 DOMAIN; X-L; APOPTOSIS; SUPPRESSION; PEPTIDE	Disruption of the complex of BECN1 with BCL2 or BCL2L1/BCL-X-L is an essential switch that turns on cellular autophagy in response to environmental stress or treatment with BH3 peptidomimetics. Recently, it has been proposed that BCL2 and BCL2L1/BCL-X-L may inhibit autophagy indirectly through a mechanism dependent on the proapoptotic BCL2 family members, BAX and BAK1. Here we report that the BH3 mimetic, ABT-737, induces autophagy in parallel with disruption of BCL2-BECN1 binding in 2 different apoptosis-deficient cell types lacking BAX and BAK1, namely in mouse embryonic fibroblasts cells and in human colon cancer HCT116 cells. We conclude that the BH3 mimetic ABT-737 induces autophagy through a BAX and BAK1-independent mechanism that likely involves disruption of BECN1 binding to antiapoptotic BCL2 family members.	[Bravo-San Pedro, Jose Manuel; Sica, Valentina; Maiuri, Maria Chiara; Kroemer, Guido] Ctr Rech Cordeliers, Equipe Labellisee Ligue Natl Canc 11, Paris, France; [Bravo-San Pedro, Jose Manuel; Sica, Valentina; Maiuri, Maria Chiara; Kroemer, Guido] INSERM, U1138, Paris, France; [Bravo-San Pedro, Jose Manuel; Sica, Valentina; Maiuri, Maria Chiara; Kroemer, Guido] Univ Paris 05, Sorbonne Paris Cite, Paris, France; [Bravo-San Pedro, Jose Manuel; Sica, Valentina; Maiuri, Maria Chiara] Gustave Roussy Canc Campus, Villejuif, France; [Bravo-San Pedro, Jose Manuel; Wei, Yongjie; Sica, Valentina; Maiuri, Maria Chiara; Kroemer, Guido] Metabol & Cell Biol Platforms, Villejuif, France; [Zou, Zhongju; Levine, Beth] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dept Internal Med, Dallas, TX 75390 USA; [Zou, Zhongju; Levine, Beth] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA; [Kroemer, Guido] Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France		Kroemer, G (corresponding author), Ctr Rech Cordeliers, Equipe Labellisee Ligue Natl Canc 11, Paris, France.	kroemer@orange.fr; beth.levine@utsouthwestern.edu	San Pedro, Jose Manuel Bravo/Q-4061-2018; Kroemer, Guido/AAY-9859-2020; KROEMER, Guido/B-4263-2013	San Pedro, Jose Manuel Bravo/0000-0002-5781-1133; KROEMER, Guido/0000-0002-9334-4405; Sica, Valentina/0000-0003-2770-5847	CPRIT [RP120718-P1]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01CA109618, U19AI109725]; Ligue contre le CancerLigue nationale contre le cancer; Agence National de la Recherche (ANR)French National Research Agency (ANR); Association pour la recherche sur le cancer (ARC)Fondation ARC pour la Recherche sur le Cancer; Canceropole Ile-de-FranceRegion Ile-de-France; Institut National du Cancer (INCa)Institut National du Cancer (INCA) France; Fondation Bettencourt-Schueller; Fondation de FranceFondation de France; Fondation pour la Recherche Medicale (FRM)Fondation pour la Recherche Medicale; European Commission (ArtForce)European CommissionEuropean Commission Joint Research Centre; European Research Council (ERC)European Research Council (ERC); LabEx Immuno-Oncology; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); SIRIC Cancer Research and Personalized Medicine (CARPEM); Paris Alliance of Cancer Research Institutes (PACRI); NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA109618] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [U19AI109725] Funding Source: NIH RePORTER	This work was supported by CPRIT grant RP120718-P1 (B.L.), NIH grants R01CA109618 and U19AI109725 (B.L.), and GK is supported by the Ligue contre le Cancer (equipe labelisee); Agence National de la Recherche (ANR); Association pour la recherche sur le cancer (ARC); Canceropole Ile-de-France; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Medicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LabEx Immuno-Oncology; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI).	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J	Singh, S; Meena, A; Luqman, S				Singh, Shilpi; Meena, Abha; Luqman, Suaib			Baicalin mediated regulation of key signaling pathways in cancer	PHARMACOLOGICAL RESEARCH			English	Review						Baicalin; Angiogenesis; Anticancer; Antiproliferative; Apoptosis; Pharmacokinetics	SHO-SAIKO-TO; PERFORMANCE LIQUID-CHROMATOGRAPHY; CELLS IN-VITRO; SUPERCRITICAL-FLUID EXTRACTION; SCUTELLARIA-BAICALENSIS; INDUCED APOPTOSIS; HERBAL MEDICINE; DOWN-REGULATION; OVARIAN-CANCER; BREAST-CANCER	Baicalin has been widely investigated against different types of malignancies both at the cellular and molecular levels over the past few years. Due to its remarkable anti-proliferative potential in numerous cancer cell lines, it has created immense interest as a potential chemotherapeutic modality compared to other flavonoids. Thus, this review focuses on the recent accomplishments of baicalin and its limitations in cancer prevention and treatment. Further, combination studies and nanoformulations using baicalin to treat cancer along with the metabolism, bioavailability, toxicity, and pharmacokinetics have been discussed. The present review explains biological source, and anti-proliferative potential of baicalin against cancers including breast, colon, hepatic, leukemia, lung, and skin, as well as the relevant mechanism of action to modulate diverse signaling pathways including apoptosis, cell cycle, invasion, and migration, angiogenesis, and autophagy. The anticancer mechanism of baicalin in orthotropic and xenograft mice models have been deliberated. The combination studies of baicalin in novel therapies as chemotherapeutic adjuvants have also been summarized. The low bioavailability, fast metabolism, and poor solubility, and other significant factors that limit the clinical use of baicalin have been examined as a challenge. The improvement in the pharmacokinetics and pharmacodynamics of baicalin with newer approaches and the gaps are highlighted, which could establish baicalin as an effective and safe compound for cancer treatment as well as help to translate its potential from bench to bedside.	[Singh, Shilpi; Meena, Abha; Luqman, Suaib] CSIR Cent Inst Med & Aromat Plants, Bioprospect & Prod Dev Div, Lucknow 226015, Uttar Pradesh, India; [Singh, Shilpi; Meena, Abha; Luqman, Suaib] Acad Sci & Innovat Res AcSIR, Ghaziabad 201002, Uttar Pradesh, India		Luqman, S (corresponding author), CSIR Cent Inst Med & Aromat Plants, Bioprospect & Prod Dev Div, Lucknow 226015, Uttar Pradesh, India.	s.luqman@cimap.res.in	Meena, Abha/AAE-2270-2022; Luqman, Suaib/M-5541-2015	MEENA, ABHA/0000-0002-1014-1486; Luqman, Suaib/0000-0001-6568-8107	CSIR-HCP [010]	CSIR-HCP 010.	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Res.	FEB	2021	164								105387	10.1016/j.phrs.2020.105387		FEB 2021	21	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	QC9LZ	WOS:000615153300038	33352232				2022-04-25	
J	Li, Y; Yang, GX; Yang, CC; Tang, P; Chen, JC; Zhang, JF; Liu, J; Ouyang, L				Li, Yang; Yang, Gaoxia; Yang, Chengcan; Tang, Pan; Chen, Juncheng; Zhang, Jifa; Liu, Jie; Ouyang, Liang			Targeting Autophagy-Related Epigenetic Regulators for Cancer Drug Discovery	JOURNAL OF MEDICINAL CHEMISTRY			English	Article							HISTONE METHYLTRANSFERASE ACTIVITY; INHIBITS AUTOPHAGY; GASTRIC-CANCER; HEPATOCELLULAR-CARCINOMA; CELL-PROLIFERATION; PROMOTES AUTOPHAGY; COLORECTAL-CANCER; SOMATIC MUTATIONS; INDUCE AUTOPHAGY; DNA METHYLATION	Existing evidence has demonstrated that epigenetic modifications (including DNA methylation, histone modifications, and microRNAs), which are associated with the occurrence and development of tumors, can directly or indirectly regulate autophagy. In particular, nuclear events induced by several epigenetic regulators can regulate the autophagic process and expression levels of tumor-associated genes, thereby promoting tumor progression. Tumor-associated microRNAs, including oncogenic and tumor-suppressive microRNAs, are of great significance to autophagy during tumor progression. Targeting autophagy with emerging epigenetic drugs is expected to be a promising therapeutic strategy for human tumors. From this perspective, we aim to summarize the role of epigenetic modification in the autophagic process and the underlying molecular mechanisms of tumorigenesis. Furthermore, the regulatory efficacy of epigenetic drugs on the autophagic process in tumors is also summarized. This perspective may provide a theoretical basis for the combined treatment of epigenetic drugs/autophagy mediators in tumors.	[Li, Yang; Yang, Gaoxia; Yang, Chengcan; Tang, Pan; Chen, Juncheng; Zhang, Jifa; Liu, Jie; Ouyang, Liang] Sichuan Univ, State Key Lab Biotherapy, Natl Clin Res Ctr Geriatr, West China Hosp, Chengdu 610041, Sichuan, Peoples R China; [Li, Yang; Yang, Gaoxia; Yang, Chengcan; Tang, Pan; Chen, Juncheng; Zhang, Jifa; Liu, Jie; Ouyang, Liang] Sichuan Univ, Canc Ctr, Natl Clin Res Ctr Geriatr, West China Hosp, Chengdu 610041, Sichuan, Peoples R China		Zhang, JF; Liu, J; Ouyang, L (corresponding author), Sichuan Univ, State Key Lab Biotherapy, Natl Clin Res Ctr Geriatr, West China Hosp, Chengdu 610041, Sichuan, Peoples R China.; Zhang, JF; Liu, J; Ouyang, L (corresponding author), Sichuan Univ, Canc Ctr, Natl Clin Res Ctr Geriatr, West China Hosp, Chengdu 610041, Sichuan, Peoples R China.	zjf298257@163.com; liujie2011@scu.edu.cn; ouyangliang@scu.edu.cn	Ouyang, Liang/A-2751-2010	Ouyang, Liang/0000-0001-5537-8834; Li, Yang/0000-0003-3855-7720	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81922064, 81874290, 81903502]; Sichuan Science and Technology Program [2020YJ0091]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2020M673268]; Health Commission of Sichuan Province [20PJ002]	This work was supported by the National Natural Science Foundation of China (grant nos. 81922064, 81874290, and 81903502), Sichuan Science and Technology Program (grant no. 2020YJ0091), China Postdoctoral Science Foundation (grant no. 2020M673268), and Scientific Research Project, Health Commission of Sichuan Province (grant no. 20PJ002).	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J	Piepoli, A; Palmieri, O; Maglietta, R; Panza, A; Cattaneo, E; Latiano, A; Laczko, E; Gentile, A; Carella, M; Mazzoccoli, G; Ancona, N; Marra, G; Andriulli, A				Piepoli, Ada; Palmieri, Orazio; Maglietta, Rosalia; Panza, Anna; Cattaneo, Elisa; Latiano, Anna; Laczko, Endre; Gentile, Annamaria; Carella, Massimo; Mazzoccoli, Gianluigi; Ancona, Nicola; Marra, Giancarlo; Andriulli, Angelo			The expression of leucine-rich repeat gene family members in colorectal cancer	EXPERIMENTAL BIOLOGY AND MEDICINE			English	Article						colorectal cancer; inflammation; autophagy; bioinformatics	TOLL-LIKE RECEPTORS; INNATE IMMUNITY; LRR PROTEINS; RAS; TRANSCRIPTOMES; IDENTIFICATION; HYBRIDIZATION; PATHOGENESIS; INFLAMMATION; RECOGNITION	This study was conducted to evaluate the association of the leucine-rich repeat (LRR) gene family with colorectal cancer (CRC). The expression of members of the LRR gene family were analyzed in 17 CRC specimens and in 59 healthy colorectal tissues by using Human Exon1.0ST microarray, and in 25 CRC specimens and 32 healthy colorectal tissues by U133Plus2.0 microarray. An association was found for 25 genes belonging to the plant-specific (PS) class of LRR genes (P = 0.05 for Exon1.0 ST and P = 0.04 for U133Plus2.0). In both data-sets, in CRC, we found down-regulation of SHOC2 (P < 0.00003) and LRRC28 (P < 0.01) and up-regulation of LRSAM1 (P < 0.000001), while up-regulation of MFHAS1 (P = 0.0005) and down-regulation of WDFY3 (P = 0.026) were found only in the Exon1.0 ST data-set. The PS LLR gene class encodes proteins that activate immune cells and might play a key role in programmed cell death and autophagy. SHOC2 and LRRC28 genes involved in RAS-mediated signaling, which hinders nutrient deprivation-induced autophagy, might be a possible link between the negative control of autophagy and tumorigenesis.	[Piepoli, Ada; Palmieri, Orazio; Panza, Anna; Latiano, Anna; Gentile, Annamaria; Andriulli, Angelo] IRCCS Casa Sollievo Sofferenza, Lab Gastroenterol, I-71013 San Giovanni Rotondo, FG, Italy; [Piepoli, Ada; Palmieri, Orazio; Panza, Anna; Latiano, Anna; Gentile, Annamaria; Andriulli, Angelo] IRCCS Casa Sollievo Sofferenza, Div Gastroenterol, I-71013 San Giovanni Rotondo, FG, Italy; [Maglietta, Rosalia; Ancona, Nicola] CNR, Ist Sistemi Intelligenti Automaz, I-70126 Bari, Italy; [Carella, Massimo] IRCCS Casa Sollievo Sofferenza, Med Genet Serv, I-71013 San Giovanni Rotondo, Italy; [Cattaneo, Elisa; Marra, Giancarlo] Univ Zurich, Inst Mol Canc Res, CH-8006 Zurich, Switzerland; [Laczko, Endre] Funct Genom Ctr Zurich, CH-8057 Zurich, Switzerland; [Mazzoccoli, Gianluigi] IRCCS Casa Sollievo Sofferenza, Div Internal Med, I-71013 San Giovanni Rotondo, FG, Italy; [Mazzoccoli, Gianluigi] IRCCS Casa Sollievo Sofferenza, Chronobiol Unit, I-71013 San Giovanni Rotondo, FG, Italy		Piepoli, A (corresponding author), IRCCS Casa Sollievo Sofferenza, Lab Gastroenterol, Viale Cappuccini 1, I-71013 San Giovanni Rotondo, FG, Italy.	a.piepoli@operapadrepio.it	Latiano, Anna/R-1965-2016; Palmieri, Orazio/J-7697-2012; Andriulli, Angelo/B-5027-2017; Ancona, Nicola/E-9971-2013; Ancona, Nicola/AAD-4772-2022; Maglietta, Rosalia/AAE-8546-2020; Piepoli, Ada/K-9299-2016; Panza, Anna/K-1989-2016; Carella, Massimo/A-2804-2014; Mazzoccoli, Gianluigi/H-2447-2016	Latiano, Anna/0000-0003-3719-2061; Palmieri, Orazio/0000-0002-0019-7929; Andriulli, Angelo/0000-0001-8862-7083; Ancona, Nicola/0000-0003-0065-0321; Maglietta, Rosalia/0000-0001-8580-4806; Piepoli, Ada/0000-0001-7487-8754; Panza, Anna/0000-0001-5840-0849; Carella, Massimo/0000-0002-6830-6829; Mazzoccoli, Gianluigi/0000-0003-3535-7635; Laczko, Endre/0000-0003-0271-3971	Italian Ministry of HealthMinistry of Health, Italy [RC1003GA53]; '5 x 1000' voluntary contributions; Progetto Strategico [PS_012]; Regione PugliaRegione Puglia; Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission [31003A-122186]	This work was supported by a grant from Italian Ministry of Health (RC1003GA53), by the '5 x 1000' voluntary contributions, by the 'Progetto Strategico' (grant PS_012) funded by the 'Regione Puglia', and by Swiss National Science Foundation (grant no. 31003A-122186). The microarrays data are accessible through Array Express (accession number E-MTAB-829) and GEO (accession number GSE21962).	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Biol. Med.	OCT	2012	237	10					1123	1128		10.1258/ebm.2012.012042			6	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	043DY	WOS:000311524300002	23045723				2022-04-25	
J	Farrall, AL; Whitelaw, ML				Farrall, A. L.; Whitelaw, M. L.			The HIF1 alpha-inducible pro-cell death gene BNIP3 is a novel target of SIM2s repression through cross-talk on the hypoxia response element	ONCOGENE			English	Article						SIM2; BNIP3; HIF1 alpha; hypoxia; cell death; cancer	DRUG-THERAPY TARGET; SINGLE-MINDED GENE; PANCREATIC-CANCER; PROSTATE-CANCER; COLORECTAL-CANCER; UP-REGULATION; EXPRESSION; AUTOPHAGY; PROTEIN; APOPTOSIS	The short isoform of single-minded 2 (SIM2s), a basic helix-loop-helix/PAS (bHLH/PAS) transcription factor, is upregulated in pancreatic and prostate tumours; however, a mechanistic role for SIM2s in these cancers is unknown. Microarray studies in prostate DU145 cells identified the pro-cell death gene, BNIP3 (Bcl-2/adenovirus E1B 19 kDa interacting protein 3), as a novel putative target of SIM2s repression. Further validation showed BNIP3 repression in several prostate and pancreatic carcinoma-derived cell lines with ectopic expression of human SIM2s. BNIP3 levels are enhanced in prostate carcinoma cells upon short interfering (si) RNA-mediated knockdown of endogenous SIM2s. Chromatin immunoprecipitation and promoter studies show that SIM2s represses BNIP3 through its activities at the proximal promoter hypoxia response element (HRE), the site through which the bHLH/PAS family member, hypoxia-inducible factor 1 alpha (HIF1 alpha), induces BNIP3. SIM2s attenuates BNIP3 hypoxic induction via the HRE, and increased hypoxic induction of BNIP3 occurs with siRNA knockdown of endogenous SIM2s in prostate PC3AR+ cells. BNIP3 is implicated in hypoxia-induced cell death processes. Prolonged treatment of PC3AR+ cells with hypoxia mimetics, DP and DMOG, confers hypoxia-induced autophagy, measured by enhanced LC3-II levels and SQSTM1/p62 turnover. We show that PC3AR+ cells expressing ectopic SIM2s have enhanced survival in these conditions. Induction of LC3-II and turnover of SQSTM1/p62 are attenuated in PC3AR+/SIM2s DMOG and hypoxia-treated cells, suggesting that SIM2s may attenuate autophagic cell death processes, perhaps through BNIP3 repression. These data show, for the first time, SIM2s cross-talk on an endogenous HRE. SIM2s' functional interference with HIF1 alpha activities on BNIP3 may indicate a novel role for SIM2s in promoting tumourigenesis. Oncogene (2009) 28, 3671-3680; doi: 10.1038/onc.2009.228; published online 10 August 2009	[Farrall, A. L.; Whitelaw, M. L.] Univ Adelaide, Discipline Biochem, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia; [Farrall, A. L.; Whitelaw, M. L.] Ctr Mol Genet Dev, Adelaide, SA, Australia		Farrall, AL (corresponding author), Univ Adelaide, Discipline Biochem, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia.	alexandra.farrall@adelaide.edu.au	Farrall, Alexandra/ABD-2079-2020	Farrall, Alexandra/0000-0002-0909-8978	Australian Cancer Research Foundation; Australian Research CouncilAustralian Research Council; Cancer Council South AustraliaCancer Council South Australia	We thank M van Bekkum and C Bindloss for their kind technical assistance, and Dr S Woods for reagents and critical reading of the manuscript. PC3AR+ cells were a kind gift from Prof W Tilley, Hanson Research Institute, Adelaide, Australia. Tet-inducible lentiviral vectors were a kind gift from Dr S Barry, Children's Health Research Institute, SA, Australia (Drabsch et al., 2007). Anti-HIF1 alpha-CAD antibody was obtained from the laboratory of Prof J Pouyssegur, CNRS UMR6543, University of Nice, France (Richard et al., 1999). We acknowledge the contribution of the Australian Cancer Research Foundation for their support of the Adelaide Microarray Facility, Adelaide, Australia, which supplied, processed and analysed the microarrays. This work was supported by grants from the Australian Research Council and the Cancer Council South Australia.	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J	Giannopoulou, E; Nikolakopoulos, A; Kotsirilou, D; Lampropoulou, A; Raftopoulou, S; Papadimitriou, E; Theocharis, AD; Makatsoris, T; Fasseas, K; Kalofonos, HP				Giannopoulou, Efstathia; Nikolakopoulos, Achilleas; Kotsirilou, Dimitra; Lampropoulou, Angeliki; Raftopoulou, Sofia; Papadimitriou, Evangelia; Theocharis, Achilleas D.; Makatsoris, Thomas; Fasseas, Konstantinos; Kalofonos, Haralabos P.			Epidermal growth factor receptor status and Notch inhibition in non-small cell lung cancer cells	JOURNAL OF BIOMEDICAL SCIENCE			English	Article						Notch intracellular domain; Epidermal growth factor receptor; Non-small cell lung cancer cells; Apoptosis; Autophagy; Cell cycle arrest	HUMAN BREAST-CANCER; SECRETASE INHIBITOR; ACQUIRED-RESISTANCE; SIGNALING PATHWAY; COLON-CANCER; CROSS-TALK; EGFR; ACTIVATION; EXPRESSION; INDUCTION	Background: Notch may behave as an oncogene or a tumor suppressor gene in lung cancer cells. Notch receptor undergoes cleavage by enzymes, including gamma-secretase, generating the active Notch intracellular domain (NICD). The aim of the present study was to investigate the effect of DAPT, gamma-secretase inhibitor, in non-small cell lung cancer (NSCLC) cells, as well as the impact of epidermal growth factor (EGF) that is over-expressed by NSCLC cells, on Notch signaling. H23, A549, H661 and HCC827 human NSCLC cell lines were used, expressing various NICD and EGF receptor (EGFR) protein levels. Results: DAPT decreased the number of H661 cells in a concentration-dependent manner, while it had a small effect on H23 and A549 cells and no effect on HCC827 cells that carry mutated EGFR. Notch inhibition did not affect the stimulatory effect of EGF on cell proliferation, while EGF prevented DAPT-induced NICD decrease in H23 and H661 cells. The type of cell death induced by DAPT seems to depend on the cell type. Conclusions: Our data indicate that inhibition of Notch cleavage may not affect cell number in the presence of EGFR mutations and that EGFR may affect Notch signalling suggesting that a dual inhibition of these pathways might be promising in NSCLC.	[Giannopoulou, Efstathia; Nikolakopoulos, Achilleas; Kotsirilou, Dimitra; Lampropoulou, Angeliki; Makatsoris, Thomas; Kalofonos, Haralabos P.] Univ Patras, Patras Med Sch, Dept Med, Div Oncol,Clin Oncol Lab, Rion 26504, Greece; [Kotsirilou, Dimitra; Papadimitriou, Evangelia] Univ Patras, Sch Hlth Sci, Dept Pharm, Mol Pharmacol Lab, Rion 26504, Greece; [Lampropoulou, Angeliki; Theocharis, Achilleas D.] Univ Patras, Dept Chem, Biochem Lab, Rion 26504, Greece; [Raftopoulou, Sofia; Fasseas, Konstantinos] Agr Univ Athens, Fac Crop Prod, Electron Microscopy Lab, GR-11855 Athens, Greece		Kalofonos, HP (corresponding author), Univ Patras, Patras Med Sch, Dept Med, Div Oncol,Clin Oncol Lab, Rion 26504, Greece.	kalofonos@upatras.gr	Papadimitriou, Evangelia/ABG-1356-2020	Papadimitriou, Evangelia/0000-0001-6429-4325; Nikolakopoulos, Achilleas/0000-0003-1681-8520; Kalofonos, Haralabos/0000-0002-3286-778X	EOGE Oncological Research Fund	We would like to thank EOGE Oncological Research Fund for financial support.	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Biomed. Sci.	OCT 24	2015	22								98	10.1186/s12929-015-0196-1			11	Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Research & Experimental Medicine	CU1SH	WOS:000363301100002	26497899	Green Published, gold			2022-04-25	
J	Hu, FQ; Song, D; Yan, YM; Huang, CS; Shen, CT; Lan, J; Chen, YQ; Liu, AY; Wu, Q; Sun, L; Xu, F; Hu, FY; Chen, LS; Luo, XL; Feng, YD; Huang, SY; Hu, JB; Wang, GH				Hu, Fuqing; Song, Da; Yan, Yumeng; Huang, Changsheng; Shen, Chentao; Lan, Jingqin; Chen, Yaqi; Liu, Anyi; Wu, Qi; Sun, Li; Xu, Feng; Hu, Fayong; Chen, Lisheng; Luo, Xuelai; Feng, Yongdong; Huang, Shengyou; Hu, Junbo; Wang, Guihua			IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation	NATURE COMMUNICATIONS			English	Article							BECLIN 1; COLORECTAL-CANCER; DRUG-RESISTANCE; INTERLEUKIN-6; INFLAMMATION; STAT3; MICROENVIRONMENT; FIBROBLASTS; PROGRESSION; IMMUNITY	Extracellular cytokines are enriched in the tumor microenvironment and regulate various important properties of cancers, including autophagy. However, the precise molecular mechanisms underlying the link between autophagy and extracellular cytokines remain to be elucidated. In the present study, we demonstrate that IL-6 activates autophagy through the IL-6/JAK2/BECN1 pathway and promotes chemotherapy resistance in colorectal cancer (CRC). Mechanistically, IL-6 triggers the interaction between JAK2 and BECN1, where JAK2 phosphorylates BECN1 at Y333. We demonstrate that BECN1 Y333 phosphorylation is crucial for BECN1 activation and IL-6-induced autophagy by regulating PI3KC3 complex formation. Furthermore, we investigate BECN1 Y333 phosphorylation as a predictive marker for poor CRC prognosis and chemotherapy resistance. Combination treatment with autophagy inhibitors or pharmacological agents targeting the IL-6/JAK2/BECN1 signaling pathway may represent a potential strategy for CRC cancer therapy. IL-6 is an important cytokine in the tumour microenvironment, but its role in regulating autophagy in cancer cells is unclear. Here the authors show that IL-6 activates autophagy in colorectal cancer through the interaction between JAK2 and autophagy regulator, BECN1, which leads to chemotherapeutic resistance.	[Hu, Fuqing; Song, Da; Huang, Changsheng; Shen, Chentao; Lan, Jingqin; Chen, Yaqi; Liu, Anyi; Wu, Qi; Xu, Feng; Hu, Fayong; Chen, Lisheng; Luo, Xuelai; Feng, Yongdong; Hu, Junbo; Wang, Guihua] Huazhong Univ Sci & Technol, Tongji Hosp, GI Canc Res Inst, Wuhan, Peoples R China; [Yan, Yumeng; Huang, Shengyou] Huazhong Univ Sci & Technol, Sch Phys, Wuhan, Hubei, Peoples R China; [Sun, Li] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Oncol, Wuhan, Peoples R China		Hu, JB; Wang, GH (corresponding author), Huazhong Univ Sci & Technol, Tongji Hosp, GI Canc Res Inst, Wuhan, Peoples R China.	jbhu@tjh.tjmu.edu.cn; ghwang@tjh.tjmu.edu.cn	Wang, Guihua/AAX-3130-2021		NSFCNational Natural Science Foundation of China (NSFC) [81773113, 81874186, 81922053]; Tongji Hospital	We are grateful to Dr. Weina Zhang, Dr. Peijing Zhang, Dr. Min Wang, and Dr. Guoxiang Jin for the suggestions on this project. We thank Shengyou Huang and his lab members for the great favor of performing protein structure data analysis and project suggestions. We thank all the health workers for help against COVID-19 in Wuhan City and all coauthors for your great work during this difficult period. This work is supported by NSFC (No. 81773113G.W., No. 81874186J.H., and No. 81922053G.W.) and startup funding from Tongji Hospital for G.W.	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Commun.	JUN 15	2021	12	1							3651	10.1038/s41467-021-23923-1			14	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	SX2EE	WOS:000665022900006	34131122	Green Published, gold			2022-04-25	
J	Zhang, YY; Xu, MF; Chen, JH; Chen, K; Zhuang, JF; Yang, YF; Liu, X; Guan, GX				Zhang, Yiyi; Xu, Meifang; Chen, Jianhua; Chen, Kui; Zhuang, Jinfu; Yang, Yuanfeng; Liu, Xing; Guan, Guoxian			Prognostic Value of the FOXK Family Expression in Patients with Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy	ONCOTARGETS AND THERAPY			English	Article						rectal cancer; neoadjuvant chemoradiotherapy; FOXK1; FOXK2; prognosis	CELL-GROWTH; PROLIFERATION; APOPTOSIS; SYSTEM; KNOCKDOWN; AUTOPHAGY; BINDING; PREDICT; GENES	Purpose: To assess the role of the expression levels of FOXK family members, FOXK1 and FOXK2, in predicting response to neo-chemoradiotherapy (NCRT) and prognosis in locally advanced rectal cancer (LARC). Methods: A total of 256 LARC patients who underwent NCRT and radical resection between 2011 and 2017 were enrolled in the present study. The patients were divided into a training dataset (n=169, 2011-2015) and a validation dataset (n=87, 2016-2017). Tumor tissues were collected before NCRT and post-surgery and were used for immunohistochemical analysis. Results: Oncomine database analysis revealed that FOXK1 and FOXK2 were overexpressed in most cancers especially in colorectal cancer. Additionally, overexpression of FOXK1 and FOXK2 was associated with poorer prognosis by the R2 database. In both our training and validation datasets, the expression of FOXK1 and FOXK2 was lower in the pathological complete response (pCR) group compared with the non-pCR group (P<0.05). Cox regression analysis demonstrated that pathological N stage (HR=1.810, 95% CI 1.159-2.827, P=0.009), FOXK1 expression (HR=5.831, 95% CI 2.925-11.625, P<0.001), and FOXK2 expression (HR=2.390, 95% CI 11.272-4.491, P=0.007) were independent predictors of disease-free survival (DFS). Based on the Cox multivariate analysis, we constructed a risk score model that served as a prognostic biomarker and had a powerful ability to predict pCR in LARC patients upon NCRT in both training and validation groups. Conclusion: Expression levels of FOXK family members were associated with chemoradiotherapy resistance and prognosis of LARC patients following NCRT and were used to construct a risk score model that is a promising biomarker for LARC.	[Zhang, Yiyi; Zhuang, Jinfu; Yang, Yuanfeng; Liu, Xing; Guan, Guoxian] Fujian Med Univ, Dept Colorectal Surg, Affiliated Hosp 1, Fuzhou 350001, Fujian, Peoples R China; [Xu, Meifang] Fujian Med Univ, Dept Pathol, Union Hosp, Fuzhou, Peoples R China; [Chen, Jianhua] Fujian Med Univ, Dept Radiol, Union Hosp, Fuzhou, Peoples R China; [Chen, Kui] Fujian Med Univ, Dept Gen Surg, Hosp Fuzhou City 1, Fuzhou, Peoples R China		Liu, X; Guan, GX (corresponding author), Fujian Med Univ, Dept Colorectal Surg, Affiliated Hosp 1, Fuzhou 350001, Fujian, Peoples R China.	fjmufylx@163.com; fjxhggx@163.com		Guan, Guoxian/0000-0001-9883-3139	Science Foundation of the Fujian ProvinceNatural Science Foundation of Fujian Province [2016J01602, 2019J0105]; Special Financial Foundation of Fujian Provincial [2015-1297]; Young and middle-aged backbone training project in the health system of Fujian province [2016-ZQN-26]; Startup Fund for Scientific Research, Fujian Medical University [2018QH2027, 2018S0130]; Professor Development Foundation of Fujian Medical University [JS11006]	This study was supported by the Science Foundation of the Fujian Province, (No. 2016J01602; 2019J0105), Special Financial Foundation of Fujian Provincial (No.2015-1297), Young and middle-aged backbone training project in the health system of Fujian province (2016-ZQN-26), the Startup Fund for Scientific Research, Fujian Medical University (2018QH2027, 2018S0130) and Professor Development Foundation of Fujian Medical University (No.JS11006).	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J	Yang, Y; Luo, H; Hui, KY; Ci, YL; Shi, KJ; Chen, G; Shi, L; Xu, CM				Yang, Yang; Luo, Hui; Hui, Kaiyuan; Ci, Yali; Shi, Kejian; Chen, Ge; Shi, Lei; Xu, Caimin			Selenite-induced autophagy antagonizes apoptosis in colorectal cancer cells in vitro and in vivo	ONCOLOGY REPORTS			English	Article						selenite; apoptosis; autophagy; colorectal cancer cells; reactive oxygen species	PROSTATE-CANCER; MEDIATED APOPTOSIS; SODIUM SELENITE; VITAMIN-E; CROSSTALK; INHIBITION; PREVENTION; RISK	In the present study, we aimed to investigate the relationship between autophagy and apoptosis in selenite-treated colorectal cancer (CRC) cells. The effects of selenite on HCT116 and SW480 cell apoptosis were investigated with an Annexin V/propidium iodide (PI) double staining kit by flow cytometry. The punctate of LC3 protein following treatment with selenite was observed by a laser scanning confocal microscope and by transmission electron microscopy. Using western blot assays, we detected the apoptotic and autophagic markers in both CRC cells and mouse xenograft tumor models. We found that sodium selenite induced autophagy in the two CRC cell lines. Consistent with the in vitro results, we observed that the expression of autophagy marker LC3 was increased. Finally, we discovered that modulation of reactive oxygen species by MnTMPyP inhibited autophagy, while H2O2 activated autophagy. These results help to elucidate the anticancer effect of selenium, providing further evidence to exploit novel anticancer drugs targeting selenium.	[Yang, Yang; Hui, Kaiyuan; Ci, Yali; Shi, Kejian; Shi, Lei; Xu, Caimin] Chinese Acad Med Sci, Peking Union Med Coll, Sch Basic Med, Inst Basic Med Sci,Dept Biochem & Mol Biol,State, Beijing 100005, Peoples R China; [Luo, Hui] Shenzhen Univ, Hlth Sci Ctr, Shenzhen 518060, Peoples R China; [Chen, Ge] CAMS, PUMC Hosp, Dept Gen Surg, Beijing 100730, Peoples R China		Shi, L (corresponding author), Chinese Acad Med Sci, Peking Union Med Coll, Sch Basic Med, Inst Basic Med Sci,Dept Biochem & Mol Biol,State, 5 Dong Dan San Tiao, Beijing 100005, Peoples R China.	shilei@ibms.pumc.edu.cn; cmxu@ibms.pumc.edu.cn	Shi, Lei/AAX-9455-2021		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31170788, 31340037, 31271565]; National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [31101018]; State Key Laboratory Special Fund [2060204]; Natural Science Foundation of BeijingBeijing Natural Science Foundation [5082015]	The present study was supported by the National Natural Science Foundation of China (nos. 31170788, 31340037 and 31271565), the National Natural Science Foundation for Young Scholars of China (no. 31101018), the State Key Laboratory Special Fund (no. 2060204), and the Natural Science Foundation of Beijing (no. 5082015).	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Rep.	MAR	2016	35	3					1255	1264		10.3892/or.2015.4484			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DB0WP	WOS:000368228900004	26676801	Green Published, hybrid, Green Submitted			2022-04-25	
J	Li, CM; Pan, B; Liu, XX; Qin, J; Wang, XH; He, BS; Pan, YQ; Sun, HL; Xu, T; Xu, XN; Zeng, KX; Wang, SK				Li, Chenmeng; Pan, Bei; Liu, Xiangxiang; Qin, Jian; Wang, Xuhong; He, Bangshun; Pan, Yuqin; Sun, Huiling; Xu, Tao; Xu, Xueni; Zeng, Kaixuan; Wang, Shukui			Long intergenic non-coding RNA LINC00485 exerts tumor-suparessive activity by regulating miR-581/EDEM1 axis in colorectal cancer	AGING-US			English	Article						linc00485; microRNA-581; EDEM1; colorectal cancer	EPITHELIAL-MESENCHYMAL TRANSITION; AUTOPHAGY; MICRORNAS	Long non-coding RNAs (lncRNA) play a vital role in colorectal cancer (CRC) progression. To investigate the role of long intergenic non-coding RNA LINC00485 in CRC, we performed in vitro functional experiments. LoVo tumor-bearing and liver metastasis mice were used as in vivo models. We found that LINC00485 expression was significantly lower in CRC tissues and cancer cells than in paired normal samples and human normal colonic epithelial cells. Lower expression of LINC00485 predicted poor prognosis in CRC patients. LINC00485 knockdown promoted the proliferation, migration, and invasion of FHC cells, while LINC00485 overexpression weakened these abilities of LoVo cells. MicroRNA miR-581 was the downstream target of LINC00485, which was downregulated in CRC samples and cancer cells compared to normal tissues and normal colonic epithelial cells. MiR-581 overexpression induced proliferation, migration, and invasion of FHC cells, while miR-581 antagomir treatment produced opposite results. MiR-581 directly targeted the 3'UTR of EDEM1 and inhibited its expression and induction of epithelial-mesenchymal transition of CRC. In mouse models, LINC00485 knockdown or down-regulation of miR-581 significantly repressed CRC cell growth and prevented CRC liver metastasis. Overall, LINC00485 suppressed CRC tumorigenesis and progression by targeting the miR-581/EDEM1 axis. LINC00485 may be a potential therapeutic target for CRC.	[Li, Chenmeng; Pan, Bei; Liu, Xiangxiang; Wang, Xuhong; Xu, Xueni; Zeng, Kaixuan; Wang, Shukui] Southeast Univ, Sch Med, Nanjing 210009, Peoples R China; [Li, Chenmeng; Pan, Bei; Liu, Xiangxiang; Qin, Jian; Wang, Xuhong; He, Bangshun; Pan, Yuqin; Sun, Huiling; Xu, Tao; Xu, Xueni; Zeng, Kaixuan; Wang, Shukui] Nanjing Med Univ, Nanjing Hosp 1, Gen Clin Res Ctr, Nanjing 210006, Peoples R China; [Wang, Shukui] Nanjing Med Univ, Jiangsu Collaborat Innovat Ctr Canc Personalized, Nanjing 211100, Peoples R China		Wang, SK (corresponding author), Southeast Univ, Sch Med, Nanjing 210009, Peoples R China.; Wang, SK (corresponding author), Nanjing Med Univ, Nanjing Hosp 1, Gen Clin Res Ctr, Nanjing 210006, Peoples R China.; Wang, SK (corresponding author), Nanjing Med Univ, Jiangsu Collaborat Innovat Ctr Canc Personalized, Nanjing 211100, Peoples R China.	sk_wang@njmu.edu.cn			National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81972806]; Jiangsu Provincial Key Research and Development Plan [BE2019614]; Key Project of Science and Technology Development of Nanjing Medicine [ZDX16001, ZKX18030]; The National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81802093]; Innovation team of Jiangsu provincial health-strengthening engineering by science and education [CXTDB20170080]; Jiangsu Youth Medical Talents Training Project [QNRC2016066, QNRC2016074]; Jiangsu 333 High-level Talents Cultivating Project [BRA201702]; Jiangsu Cancer Personalized Medicine Collaborative Innovation Center	This project was supported by grants from The National Nature Science Foundation of China (No. 81972806), Jiangsu Provincial Key Research and Development Plan (BE2019614), Key Project of Science and Technology Development of Nanjing Medicine (ZDX16001) to SKW; The National Nature Science Foundation of China (No. 81802093) to HLS; Innovation team of Jiangsu provincial health-strengthening engineering by science and education (CXTDB20170080); Jiangsu Youth Medical Talents Training Project to BSH (QNRC2016066) and YQP (QNRC2016074); Key Project of Science and Technology Development of Nanjing Medicine (ZKX18030, breast cancer); Jiangsu 333 High-level Talents Cultivating Project (Gastric cancer, no. BRA201702) and Jiangsu Cancer Personalized Medicine Collaborative Innovation Center.	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J	Zaytseva, YY; Harris, JW; Mitov, MI; Kim, JT; Butterfield, DA; Lee, EY; Weiss, HL; Gao, T; Evers, BM				Zaytseva, Yekaterina Y.; Harris, Jennifer W.; Mitov, Mihail I.; Kim, Ji Tae; Butterfield, D. Allan; Lee, Eun Y.; Weiss, Heidi L.; Gao, Tianyan; Evers, B. Mark			Increased expression of fatty acid synthase provides a survival advantage to colorectal cancer cells via upregulation of cellular respiration	ONCOTARGET			English	Article						FASN; colorectal cancer; energy homeostasis; metastasis; metabolic stress	ACTIVATED PROTEIN-KINASE; PROSTATE-CANCER; LIPID-SYNTHESIS; TUMOR-GROWTH; METABOLISM; INHIBITION; AUTOPHAGY; TARGETS; AMPK; METASTASIS	Fatty acid synthase (FASN), a lipogenic enzyme, is upregulated in colorectal cancer (CRC). Increased de novo lipid synthesis is thought to be a metabolic adaptation of cancer cells that promotes survival and metastasis; however, the mechanisms for this phenomenon are not fully understood. We show that FASN plays a role in regulation of energy homeostasis by enhancing cellular respiration in CRC. We demonstrate that endogenously synthesized lipids fuel fatty acid oxidation, particularly during metabolic stress, and maintain energy homeostasis. Increased FASN expression is associated with a decrease in activation of energy-sensing pathways and accumulation of lipid droplets in CRC cells and orthotopic CRCs. Immunohistochemical evaluation demonstrated increased expression of FASN and p62, a marker of autophagy inhibition, in primary CRCs and liver metastases compared to matched normal colonic mucosa. Our findings indicate that overexpression of FASN plays a crucial role in maintaining energy homeostasis in CRC via increased oxidation of endogenously synthesized lipids. Importantly, activation of fatty acid oxidation and consequent downregulation of stress-response signaling pathways may be key adaptation mechanisms that mediate the effects of FASN on cancer cell survival and metastasis, providing a strong rationale for targeting this pathway in advanced CRC.	[Zaytseva, Yekaterina Y.; Harris, Jennifer W.; Mitov, Mihail I.; Kim, Ji Tae; Butterfield, D. Allan; Lee, Eun Y.; Weiss, Heidi L.; Gao, Tianyan; Evers, B. Mark] Univ Kentucky, Markey Canc Ctr, Lexington, KY 40508 USA; [Harris, Jennifer W.; Evers, B. Mark] Univ Kentucky, Dept Surg, Lexington, KY USA; [Butterfield, D. Allan] Univ Kentucky, Dept Chem, Lexington, KY 40506 USA; [Lee, Eun Y.] Univ Kentucky, Pathol & Lab Med, Lexington, KY USA		Evers, BM (corresponding author), Univ Kentucky, Markey Canc Ctr, Lexington, KY 40508 USA.	mark.evers@uky.edu			NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [T32 CA165990]; NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30 CA177558]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [T32CA160003, T32CA165990, P30CA177558] Funding Source: NIH RePORTER	This research was supported by NIH grant T32 CA165990 and NCI grant P30 CA177558 (for shared resource facilities).	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J	Wu, YH; Wu, YR; Li, B; Yan, ZY				Wu, Yan-Hong; Wu, Yu-Rui; Li, Bo; Yan, Zhu-Yun			Cryptotanshinone: A review of its pharmacology activities and molecular mechanisms	FITOTERAPIA			English	Review						Cryptotanshinone; Pharmacology; Anti-tumor; Molecular mechanisms; Signaling pathways	AUTOPHAGIC CELL-DEATH; COLON-CANCER CELLS; SALVIA-MILTIORRHIZA; CARDIAC FIBROSIS; SIGNALING PATHWAY; INDUCED APOPTOSIS; HERBAL COMPOUND; DOWN-REGULATION; TANSHINONE IIA; CYCLE ARREST	As a natural quinone compound, the medicinal value of cryptotanshinone (CT) has received increasing attentions, but there is no systematic literature review that describes the pharmacological activity of CT. This paper reviewed the pharmacology researches of CT, with a primary focus on its anti-tumor activity. We also discussed the underlying molecular mechanisms, and proposed future outlooks. In addition to anti-tumor activity, CT was found to have anti-inflammatory, neuroprotective, cardioprotective, visceral protective, anti-metabolic disorders and other abilities. Furthermore, the potential molecular mechanisms contributing to the anti-tumor effect of CT likely involve the following aspects: the induction of apoptosis, targeting of ER and AR, reversion of MDR, combined pharmacotherapy, and the inhibition of cell proliferation, migration, and invasion. We also found that different pharmacological effects involved various signaling pathways. Among them, STAT3-related signaling pathways played a vital role in the CT-mediated induction of tumor cell apoptosis and proliferation, while NF-kappa B signal pathway also was essential for inhibition of inflammation by CT. Furthermore, CT could significantly enhance the activities of several anticancer drugs and reverse their resistances in tumors. Therefore, we proposed suggestions for future studies of CT, including enhancing anti-tumor activity by targeting STAT3-related receptors, targeting NF-kappa B-related pathways to inhibit inflammatory responses, enhancing anti-tumor efficacy by combining with anti-tumor drugs, and further studying the dose-effect relationship to ensure safer and more effective applications of CT.	[Wu, Yan-Hong; Wu, Yu-Rui; Li, Bo; Yan, Zhu-Yun] Chengdu Univ Tradit Chinese Med, Sch Pharm, Key Lab Characterist Chinese Med Resources Southw, Chengdu, Peoples R China		Yan, ZY (corresponding author), Chengdu Univ Tradit Chinese Med, Sch Pharm, Chengdu, Peoples R China.	yanzhuyun@cdutcm.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81573537, 81973416]	This study was supported by grants from the National Natural Science Foundation of China (81573537, 81973416).	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Y., 2019, FRONT NEUROL, V10; Zhao JL, 2011, MOLECULES, V16, P2259, DOI 10.3390/molecules16032259; Zhao WW, 2016, CELL ADHES MIGR, V10, P248, DOI 10.1080/19336918.2015.1119361; Zhou J, 2014, ASIAN PAC J CANCER P, V15, P2439, DOI 10.7314/APJCP.2014.15.6.2439; Zhou Y, 2019, FRONT NEUROSCI-SWITZ, V13, DOI 10.3389/fnins.2019.00852; Zhu R, 2019, J CELL BIOCHEM, V120, P13354, DOI 10.1002/jcb.28609; Zhu WX, 2017, MOL MED REP, V16, P9361, DOI 10.3892/mmr.2017.7824; Zhu ZJ, 2016, MOL CARCINOGEN, V55, P1399, DOI 10.1002/mc.22383; Zu RL, 2019, JUNDISHAPUR J MICROB, V12, DOI 10.5812/jjm.83922	140	14	14	2	28	ELSEVIER	AMSTERDAM	RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS	0367-326X	1873-6971		FITOTERAPIA	Fitoterapia	SEP	2020	145								104633	10.1016/j.fitote.2020.104633			12	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	LY7ME	WOS:000540710700011	32445662				2022-04-25	
J	Su, YY; Yao, SW; Zhao, S; Li, JC; Li, HY				Su, Yanyan; Yao, Shuwen; Zhao, Shill; Li, Jinchun; Li, Hongyan			LncRNA CCAT1 functions as apoptosis inhibitor in podocytes via autophagy inhibition	JOURNAL OF CELLULAR BIOCHEMISTRY			English	Article						autophagy; lncRNA CCAT1; PI3K; Akt signaling; podocyte	LONG NONCODING RNA; NECROSIS-FACTOR-ALPHA; CELL-PROLIFERATION; C-MYC; EXPRESSION; INJURY	Podocyte apoptosis importantly contributes to various kidney diseases. Long noncoding RNAs Colon cancer-associated transcript-1 (CCAT-1) has been demonstrated for a critical role in cell proliferation. In the present study, the relationship between CCAT1 and popdocyte impairment, and the underlying mechanism was investigated. Podocytes were isolated from mice and then treated with tumor necrosis factor-alpha to simulate podocyte injury. After developed CCAT1 overexpression or knockdown, cell viabilities were determined with the CCK-8 assay, apoptosis was examined with Flow cytometry, the autophagy was observed by Western blot. Furthermore, phosphorylated PI3K and Akt expressions were examined. We found that after CCAT1 overexpression, the cell viability was significantly increased, apoptosis was significantly decreased, and autophagy was significantly inhibited, which was indicated by induced P62, LC3B-I and decreased LC3B-II. In addition, CCAT1 overexpression induced the levels of phosphorylated PI3K and Akt. With Rap treatment, these effects by CCAT1 were reversed. Furthermore, the results contrary to the effects by CCAT1 overexpression were presented after CCAT1 knockdown, and this was inhibited by 3-MA. Taken together, our results suggested that CCAT1 induction critically participated in apoptosis inhibition in podocytes through autophagy inhibition via increasing PI3K/Akt signaling. This might act as a promising therapeutic intervention for renal diseases associated with podocyte apoptosis.	[Su, Yanyan; Yao, Shuwen; Zhao, Shill; Li, Jinchun; Li, Hongyan] Southern Med Univ, Huadu Dist Peoples Hosp Guangzhou, Dept Nephrol, 22 Baohua Rd, Guangzhou, Guangdong, Peoples R China		Li, HY (corresponding author), Southern Med Univ, Huadu Dist Peoples Hosp Guangzhou, Dept Nephrol, 22 Baohua Rd, Guangzhou, Guangdong, Peoples R China.	lihy0726@126.com			Guangzhou Medical Key Discipline Construction Project [2017-2019]	Guangzhou Medical Key Discipline Construction Project, Grant/Award Number: 2017-2019	Batista PJ, 2013, CELL, V152, P1298, DOI 10.1016/j.cell.2013.02.012; Cellesi F, 2015, CURR OPIN NEPHROL HY, V24, P239, DOI 10.1097/MNH.0000000000000124; Chen SA, 2017, MOL CELL BIOCHEM, V434, P135, DOI 10.1007/s11010-017-3043-8; Chung CH, 2015, NEPHRON EXTRA, V5, P1, DOI 10.1159/000369576; Dong CL, 2015, EXP CELL RES, V337, P146, DOI 10.1016/j.yexcr.2015.04.005; Fornoni A, 2011, SCI TRANSL MED, V3, DOI 10.1126/scitranslmed.3002231; Guo XQ, 2017, J CANCER RES CLIN, V143, P555, DOI 10.1007/s00432-016-2268-3; He XL, 2014, TUMOR BIOL, V35, P12181, DOI 10.1007/s13277-014-2526-4; Inoki K, 2014, SEMIN NEPHROL, V34, P2, DOI 10.1016/j.semnephrol.2013.11.002; Jiang Y, 2018, NAT COMMUN, V9, DOI 10.1038/s41467-018-06081-9; Kim WY, 2012, NEPHROLOGY, V17, P148, DOI 10.1111/j.1440-1797.2011.01541.x; Kume S, 2014, SEMIN NEPHROL, V34, P9, DOI 10.1016/j.semnephrol.2013.11.003; Lan AP, 2015, NEPHROL DIAL TRANSPL, V30, P385, DOI 10.1093/ndt/gfu196; Lenoir O, 2016, KIDNEY INT, V90, P950, DOI 10.1016/j.kint.2016.04.014; Li D, 2016, BIOSCIENCE REP, V36, DOI 10.1042/BSR20160086; Liu J, 2018, PLOS ONE, V13, DOI 10.1371/journal.pone.0197158; Liu NW, 2017, ELECTRON J QUAL THEO, P1, DOI 10.14232/ejqtde.2017.1.35; Liu Y, 2017, CELL DEATH DIS, V8, DOI 10.1038/cddis.2017.414; Lu L, 2017, ONCOTARGET, V8, P19285, DOI 10.18632/oncotarget.15195; Mundel P, 2002, J AM SOC NEPHROL, V13, P3005, DOI 10.1097/01.ASN.0000039661.06947.FD; Nagata M, 2016, KIDNEY INT, V89, P1221, DOI 10.1016/j.kint.2016.01.012; Nazio F, 2013, NAT CELL BIOL, V15, P406, DOI 10.1038/ncb2708; Ryu M, 2012, J PATHOL, V226, P120, DOI 10.1002/path.2979; Schmitt AM, 2016, CANCER CELL, V29, P452, DOI 10.1016/j.ccell.2016.03.010; Song ZX, 2014, METABOLISM, V63, P1324, DOI 10.1016/j.metabol.2014.06.013; Wang QS, 2017, CELL CYCLE, V16, P795, DOI 10.1080/15384101.2017.1301334; Wang XT, 2008, NATURE, V454, P126, DOI 10.1038/nature06992; Xiang JF, 2014, CELL RES, V24, P513, DOI 10.1038/cr.2014.35; Yang TZ, 2018, BRAZ J MED BIOL RES, V51, DOI [10.1590/1414-431X20187046, 10.1590/1414-431x20187046]; Zhang EB, 2017, NUCLEIC ACIDS RES, V45, P3086, DOI 10.1093/nar/gkw1247; Zhang J, 2017, ONCOTARGET, V8, P68059, DOI 10.18632/oncotarget.19155; Zhang XF, 2015, INT J CLIN EXP PATHO, V8, P9440; Zhao SY, 2018, LECT N BIOINFORMAT, V10847, P38, DOI 10.1007/978-3-319-94968-0_4	33	6	8	0	5	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0730-2312	1097-4644		J CELL BIOCHEM	J. Cell. Biochem.	JAN	2020	121	1					621	631		10.1002/jcb.29307		AUG 2019	11	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	JQ1VC	WOS:000484291500001	31468575	hybrid, Green Published			2022-04-25	
J	Douglass, S; Goyal, A; Iozzo, RV				Douglass, Stephen; Goyal, Atul; Iozzo, Renato V.			The role of perlecan and endorepellin in the control of tumor angiogenesis and endothelial cell autophagy	CONNECTIVE TISSUE RESEARCH			English	Review						Angiogenesis; autophagy; perlecan; LG domains; Peg3	HEPARAN-SULFATE PROTEOGLYCAN; SCHWARTZ-JAMPEL-SYNDROME; FIBROBLAST-GROWTH-FACTOR; COLON-CARCINOMA-CELLS; BASEMENT-MEMBRANE PROTEOGLYCANS; EXTRACELLULAR-MATRIX; PROTEIN CORE; FACTOR-RECEPTOR; IN-VIVO; SIGNALING PATHWAYS	During tumor growth and angiogenesis there is a dynamic remodeling of tissue architecture often accompanied by the release of extracellular matrix constituents full of biological activity. One of the key constituents of the tumor microenvironment is the large heparan sulfate proteoglycan perlecan. This proteoglycan, strategically located at cell surfaces and within basement membranes, is a well-defined pro-angiogenic molecule when intact. However, when partially processed by proteases released during cancer remodeling and invasion, the C-terminal fragment of perlecan, known as endorepellin, has opposite effects than its parent molecule. Endorepellin is a potent inhibitor of angiogenesis by exerting a dual receptor antagonism by simultaneously engaging VEGFR2 and alpha 2 beta 1 integrin. Signaling through the a2b1 integrin leads to actin disassembly and block of endothelial cell migration, necessary for capillary morphogenesis. Signaling through the VEGFR2 induces dephosphorylation of the receptor via activation of SHP-1 and suppression of downstream proangiogenic effectors, especially attenuating VEGFA expression. A novel and emerging role of endorepellin is its ability to evoke autophagy by activating Peg3 and various canonical autophagic markers. This effect is specific for endothelial cells as these are the primary cells expressing both VEGFR2 and a2b1 integrin. Thus, an endogenous fragment of a ubiquitous proteoglycan can regulate both angiogenesis and autophagy through a dual receptor antagonism. The biological properties of this natural endogenous protein place endorepellin as a potential therapeutic agent against cancer or diseases where angiogenesis is prominent.	Thomas Jefferson Univ, Sidney Kimmel Med Coll, Kimmel Canc Ctr, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA; Thomas Jefferson Univ, Sidney Kimmel Med Coll, Kimmel Canc Ctr, Canc Cell Biol & Signalling Program, Philadelphia, PA 19107 USA		Iozzo, RV (corresponding author), Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Pathol Anat & Cell Biol, 1020 Locust St,Suite 336 JAH, Philadelphia, PA 19107 USA.	renato.iozzo@jefferson.edu	Douglass, Stephen/ABH-4878-2020; Iozzo, Renato/AAS-1980-2020	Douglass, Stephen/0000-0003-1562-2235; Iozzo, Renato/0000-0002-5908-5112	National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [RO1 CA39481, RO1 CA47282, RO1 CA164462]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA039481, R01CA047282, R01CA164462] Funding Source: NIH RePORTER	The authors declare that they have no competing interests. All the authors were involved in drafting the article, and approved the final version to be published. The original research was supported in part by National Institutes of Health Grants RO1 CA39481, RO1 CA47282 and RO1 CA164462.	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Tissue Res.		2015	56	5			SI		381	391		10.3109/03008207.2015.1045297			11	Cell Biology; Orthopedics	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Orthopedics	DD3KY	WOS:000369822300005	26181327	Green Submitted, Green Accepted			2022-04-25	
J	Keles, U; Iscan, E; Yilmaz, HE; Karakulah, G; Suner, A; Bal, E; Tasdemir, N; Cavga, AD; Ekin, U; Mutlu, Z; Kahyaoglu, S; Serdar, MA; Atabey, N; Ozturk, M				Keles, Umur; Iscan, Evin; Yilmaz, Huriye Erbak; Karakulah, Gokhan; Suner, Asli; Bal, Erhan; Tasdemir, Nilgun; Cavga, Ayse Derya; Ekin, Umut; Mutlu, Zeynep; Kahyaoglu, Sila; Serdar, Muhittin A.; Atabey, Nese; Ozturk, Mehmet			Differential expression of full-length and NH2 terminally truncated FAM134B isoforms in normal physiology and cancer	AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY			English	Article						autophagy; endoplasmic reticulum; ER-phagy; gene expression; gene knockout; hepatocellular carcinoma; reticulophagy	GOLGI PROTEIN; MICE; METABOLISM; AUTOPHAGY; CHOLESTEROL; INHIBITION; STARVATION	Selective autophagy of the endoplasmic reticulum (ER), namely ER-phagy, is mediated by ER-localized receptors, which are recognized and sequestered by GABARAP/LC3B-decorated phagophores and transferred to lysosomes for degradation. Being one such receptor, FAM134B plays critical roles in cellular processes such as protein quality control and neuronal survival. FAM134B has also been associated with different cancers, although its exact role remains elusive. We report here that the FAM134B gene encodes not one but at least two different protein isoforms: the full-length and the NH2 terminally truncated forms. Their relative expression shows extreme variation, both within normal tissues and among cancer types. Expression of full-length FAM134B is restricted to the brain, testis, spleen, and prostate. In contrast, NH2 terminally truncated FAM134B is dominant in the heart, skeletal muscle, kidney, pancreas, and liver. We compared wild-type and knockout mice to study the role of the Fam134b gene in starvation. NH2 terminally truncated FAM134B-2 was induced in the liver, skeletal muscle, and heart but not in the pancreas and stomach following starvation. Upon starvation, Fam134b(-/-) mice differed from wild-type mice by less weight loss and less hyperaminoacidemic and hypocalcemic response but increased levels of serum albumin, total serum proteins, and a-amylase. Interestingly, either NH2 terminally truncated FAM134B or both isoforms were downregulated in liver, lung, and colon cancers. In contrast, upregulation was observed in stomach and chromophobe kidney cancers. NEW & NOTEWORTHY We reported tissues expressing FAM134B2 such as the kidney, muscle, heart, and pancreas, some of which exhibit stimulated expression upon nutrient starvation. We also demonstrated the effect of Fam134b deletion during ad libitum and starvation conditions. Resistance to weight loss and hypocalcemia, accompanied by an increase in serum albumin and alpha-amylase levels, indicate critical roles of Fam134b in physiology. Furthermore, the differential expression of FAM134B isoforms was shown to be significantly dysregulated in human cancers.	[Keles, Umur; Iscan, Evin; Karakulah, Gokhan; Bal, Erhan; Ekin, Umut; Mutlu, Zeynep; Kahyaoglu, Sila; Atabey, Nese; Ozturk, Mehmet] Izmir Biomed & Genome Ctr, Izmir, Turkey; [Keles, Umur; Iscan, Evin; Yilmaz, Huriye Erbak; Karakulah, Gokhan; Ekin, Umut] Dokuz Eylul Univ, Izmir Int Biomed & Genome Inst, Izmir, Turkey; [Suner, Asli] Ege Univ, Dept Biostat & Med Informat, Izmir, Turkey; [Tasdemir, Nilgun; Cavga, Ayse Derya] Bilkent Univ, Dept Mol Biol & Genet, Ankara, Turkey; [Serdar, Muhittin A.] Acibadem Univ, Dept Biochem, Istanbul, Turkey		Ozturk, M (corresponding author), Izmir Biomed & Genome Ctr, Izmir, Turkey.	mehmet.orturk@ibg.edu.tr	Atabey, Nese/A-1853-2018; İşcan, Evin/AAA-4818-2022; SUNER, ASLI/C-1032-2012; OZTURK, MEHMET/AAS-7241-2021	Atabey, Nese/0000-0003-4966-2980; SUNER, ASLI/0000-0002-6872-9901; OZTURK, MEHMET/0000-0002-6092-9706; Cavga, Ayse Derya/0000-0001-5017-5042; Keles, Umur/0000-0002-6771-3721	Dokuz Eylul University, Department of Scientific Research ProjectsDokuz Eylul University [2014.KB.SAG.047]; Izmir Biomedicine and Genome Center's (IBG) institutional funds; Common Fund of the Office of the Director of the National Institutes of Health; National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI); National Human Genome Research InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI); National Heart, Lung, and Blood InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI); National Institute on Drug AbuseUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA)European Commission; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH); National Institute of Neurological Disorders and StrokeUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS)	This study is supported by Dokuz Eylul University, Department of Scientific Research Projects (with the Project code 2014.KB.SAG.047), and Izmir Biomedicine and Genome Center's (IBG) institutional funds. The GenotypeTissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by the National Cancer Institute, National Human Genome Research Institute, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of Mental Health, and National Institute of Neurological Disorders and Stroke. The data used for the analyses described in this article were obtained from the GTEx Portal on 11/14/2018 and/or dbGaP Accession No. phs000424.v3.p1.	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J. Physiol.-Gastroint. Liver Physiol.	DEC	2020	319	6					G733	G747		10.1152/ajpgi.00094.2020			15	Gastroenterology & Hepatology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology; Physiology	RC3LQ	WOS:000632705700001	33052704	Green Submitted, Green Published			2022-04-25	
J	Nicoli, ER; Dumitrescu, T; Uscatu, CD; Popescu, FD; Streata, I; Sosoi, SS; Ivanov, P; Dumitrescu, A; Barbalan, A; Lungulescu, D; Petrescu, F; Schenker, M; Verdes, D; Saftoiu, A				Nicoli, Elena-Raluca; Dumitrescu, Theodor; Uscatu, Constantin-Daniel; Popescu, Florin-Dan; Streata, Ioana; Sosoi, Simona Serban; Ivanov, Petar; Dumitrescu, Alexandra; Barbalan, Alexandru; Lungulescu, Dan; Petrescu, Florin; Schenker, Michael; Verdes, Doina; Saftoiu, Adrian			Determination of autophagy gene ATG16L1 polymorphism in human colorectal cancer	ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY			English	Article						ATG16L1; gene polymorphism; colorectal cancer; autophagy	GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; SUSCEPTIBILITY; INFLAMMATION; CELLS; IL23R; PHENOTYPE; INFECTION; IMMUNITY; VARIANT	Autophagy has emerged not only as an essential repair mechanism to degrade damaged organelles and proteins but also as a major player in protection of tumor cells from multiple stresses. It was shown that autophagy gene polymorphisms are correlated with development of chronic inflammatory lesions, which represent a risk factor for colorectal tumors. In this study, we aimed to determine if ATG16L1 +898A>G (Thr300Ala) polymorphism is associated with an increased risk of developing colorectal cancer (CRC) and to establish correlations between ATG16L1 genotypes and the major clinical and morphological parameters. We observed that subjects carrying GG genotype were at a higher risk for CRC (OR 1.99, 95% Cl: 1.02-3.91, p=0.039) when compared with the more frequent AA genotype, furthermore this was even more consistent in male subjects (OR 2.72, 95% Cl: 1.11-6.63, p=0.019) but not in female subjects (OR 1.29, 95% Cl: 0.43-3.86, p=0.652). In addition, we noticed a correlation between ATG16L1 GO genotype and tumor stage in moderately and poorly differentiated CRC cases. GG genotype carrying patients were at a higher risk for CRC (OR 5.19, 95% Cl: 1.50-17.87, p=0.002) when compared with the more frequent AA genotype. Such correlation suggests a possible role of autophagy gene polymorphisms in the development of human colorectal cancer.	[Nicoli, Elena-Raluca; Uscatu, Constantin-Daniel; Streata, Ioana; Sosoi, Simona Serban] Univ Med & Pharm Craiova, Human Genom Lab, Craiova 200638, Romania; [Nicoli, Elena-Raluca; Ivanov, Petar] Univ Med & Pharm Craiova, Dept Pharmacol, Craiova 200638, Romania; [Dumitrescu, Theodor] Univ Med & Pharm Craiova, Dept Surg, Craiova 200638, Romania; [Dumitrescu, Theodor; Barbalan, Alexandru] Emergency Cty Hosp, Med Surg Clin 2, Craiova, Romania; [Uscatu, Constantin-Daniel] Emergency Cty Hosp, Dept Pathol, Craiova, Romania; [Popescu, Florin-Dan] Carol Davila Univ Med & Pharm, Dept Allergy & Clin Immunol, Bucharest, Romania; [Dumitrescu, Alexandra] Emergency Cty Hosp, Clin Med Oncol, Craiova, Romania; [Barbalan, Alexandru; Saftoiu, Adrian] Univ Med & Pharm Craiova, Res Ctr Gastroenterol & Hepatol, Craiova 200638, Romania; [Lungulescu, Dan] OncoLab Med Ctr, Craibva, Romania; [Petrescu, Florin] Univ Med & Pharm Craiova, Dept Med Semiol, Craiova 200638, Romania; [Schenker, Michael] Univ Med & Pharm Craiova, Dept Oncol, Craiova 200638, Romania; [Verdes, Doina] Victor Babes Univ Med & Pharm, Dept Cellular & Mol Biol, Timisoara, Romania; [Saftoiu, Adrian] Univ Copenhagen, Fac Med & Hlth Sci, DK-1168 Copenhagen, Denmark; [Saftoiu, Adrian] Univ Copenhagen, Herlev Hosp, Gastrointestinal Unit, DK-1168 Copenhagen, Denmark		Nicoli, ER (corresponding author), Univ Med & Pharm Craiova, Human Genom Lab, 66 1 May Ave, Craiova 200638, Romania.	raluca@nicoli.ro	Schenker, Michael/AAD-6920-2022; Nicoli, Elena-Raluca/F-3968-2011; Popescu, Florin-Dan/AAL-4750-2021; Saftoiu, Adrian/C-2792-2011; Lungulescu, Dan/F-4085-2017	Schenker, Michael/0000-0003-2645-6391; Nicoli, Elena-Raluca/0000-0002-5545-630X; Popescu, Florin-Dan/0000-0001-6316-3155; Saftoiu, Adrian/0000-0001-7993-8269; Dumitrescu, Theodor Viorel/0000-0002-2485-7821; Calota, Firmilian/0000-0002-2689-5477	Sectorial Operational Programme Human Resources Development; European Social FundEuropean Social Fund (ESF); Romanian GovernmentRomanian Government; Romanian National Authority for Scientific Research, CNCS-UEFISCDIConsiliul National al Cercetarii Stiintifice (CNCS)Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (UEFISCDI) [PNII-CT-ERC-2012-1];  [POSDRU/107/1.5/S/82705]	Elena-Raluca Nicoli acknowledges the support of the research grant POSDRU/107/1.5/S/82705 project, supported by Sectorial Operational Programme Human Resources Development, financed by the European Social Fund and the Romanian Government. First author also acknowledges that this work was supported by a grant of the Romanian National Authority for Scientific Research, CNCS-UEFISCDI, project ID PNII-CT-ERC-2012-1.	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J. Morphol. Embryol.		2014	55	1					57	62					6	Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Developmental Biology	AF4BL	WOS:000334656300008	24715166				2022-04-25	
J	Gabryanczyk, A; Klimczak, S; Szymczak-Pajor, I; Sliwinska, A				Gabryanczyk, Anna; Klimczak, Sylwia; Szymczak-Pajor, Izabela; Sliwinska, Agnieszka			Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						vitamin D deficiency; type 2 diabetes (T2DM); cancer	CIRCULATING 25-HYDROXYVITAMIN D; HUMAN-COLON-CANCER; NECROSIS-FACTOR-ALPHA; ROR-GAMMA EXPRESSION; PROTEIN-KINASE CK2; D-BINDING PROTEIN; CELL LUNG-CANCER; D-RECEPTOR FOKI; FACTOR-KAPPA-B; PROSTATE-CANCER	There is mounting evidence that type 2 diabetes mellitus (T2DM) is related with increased risk for the development of cancer. Apart from shared common risk factors typical for both diseases, diabetes driven factors including hyperinsulinemia, insulin resistance, hyperglycemia and low grade chronic inflammation are of great importance. Recently, vitamin D deficiency was reported to be associated with the pathogenesis of numerous diseases, including T2DM and cancer. However, little is known whether vitamin D deficiency may be responsible for elevated cancer risk development in T2DM patients. Therefore, the aim of the current review is to identify the molecular mechanisms by which vitamin D deficiency may contribute to cancer development in T2DM patients. Vitamin D via alleviation of insulin resistance, hyperglycemia, oxidative stress and inflammation reduces diabetes driven cancer risk factors. Moreover, vitamin D strengthens the DNA repair process, and regulates apoptosis and autophagy of cancer cells as well as signaling pathways involved in tumorigenesis i.e., tumor growth factor beta (TGF beta), insulin-like growth factor (IGF) and Wnt-beta-Cathenin. It should also be underlined that many types of cancer cells present alterations in vitamin D metabolism and action as a result of Vitamin D Receptor (VDR) and CYP27B1 expression dysregulation. Although, numerous studies revealed that adequate vitamin D concentration prevents or delays T2DM and cancer development, little is known how the vitamin affects cancer risk among T2DM patients. There is a pressing need for randomized clinical trials to clarify whether vitamin D deficiency may be a factor responsible for increased risk of cancer in T2DM patients, and whether the use of the vitamin by patients with diabetes and cancer may improve cancer prognosis and metabolic control of diabetes.	[Gabryanczyk, Anna; Szymczak-Pajor, Izabela; Sliwinska, Agnieszka] Med Univ Lodz, Dept Nucle Acid Biochem, 251 Pomorska Str, PL-92213 Lodz, Poland; [Klimczak, Sylwia] Med Univ Lodz, Student Sci Soc Civilizat Dis, 251 Pomorska, PL-92213 Lodz, Poland		Sliwinska, A (corresponding author), Med Univ Lodz, Dept Nucle Acid Biochem, 251 Pomorska Str, PL-92213 Lodz, Poland.	anna.gabryanczyk@umed.lodz.pl; sylwia.cichuta@stud.umed.lodz.pl; izabela.szymczak@umed.lodz.pl; agnieszka.sliwinska@umed.lodz.pl		Szymczak-Pajor, Izabela/0000-0002-6545-579X; Sliwinska, Agnieszka/0000-0002-6864-0704	Medical University of Lodz [503/1-15901/503-21-001]	This paper was supported by the grant from Medical University of Lodz (No. 503/1-15901/503-21-001)	Abdelbaset-Ismail A, 2016, J OVARIAN RES, V9, DOI 10.1186/s13048-016-0235-x; Agrawal A, 2003, IMMUNOLOGY, V108, P539, DOI 10.1046/j.1365-2567.2003.01608.x; Aguilera O, 2007, CARCINOGENESIS, V28, P1877, DOI 10.1093/carcin/bgm094; Akhter J, 1997, DIS COLON RECTUM, V40, P317, DOI 10.1007/BF02050422; 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J. Mol. Sci.	JUN	2021	22	12							6444	10.3390/ijms22126444			33	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	SZ0SB	WOS:000666285300001	34208589	gold, Green Published			2022-04-25	
J	Huang, XM; Huang, JJ; Du, JJ; Zhang, N; Long, Z; Yang, Y; Zhong, FF; Zheng, BW; Shen, YF; Huang, Z; Qin, X; Chen, JH; Lin, QY; Lin, WJ; Ma, WZ				Huang, Xiao-ming; Huang, Jia-jun; Du, Jing-jing; Zhang, Na; Long, Ze; Yang, You; Zhong, Fang-fang; Zheng, Bo-wen; Shen, Yun-fu; Huang, Zhe; Qin, Xiang; Chen, Jun-he; Lin, Qian-yu; Lin, Wan-jun; Ma, Wen-zhe			Autophagy inhibitors increase the susceptibility of KRAS-mutant human colorectal cancer cells to a combined treatment of 2-deoxy-D-glucose and lovastatin	ACTA PHARMACOLOGICA SINICA			English	Article						human colorectal cancers; lovastatin; 2DG; glycolysis; OXPHOS; autophagy; chloroquine; hydroxychloroquine		RAS-driven colorectal cancer relies on glucose metabolism to support uncontrolled growth. However, monotherapy with glycolysis inhibitors like 2-deoxy-D-glucose causes limited effectiveness. Recent studies suggest that anti-tumor effects of glycolysis inhibition could be improved by combination treatment with inhibitors of oxidative phosphorylation. In this study we investigated the effect of a combination of 2-deoxy-D-glucose with lovastatin (a known inhibitor of mevalonate pathway and oxidative phosphorylation) on growth of KRAS-mutant human colorectal cancer cell lines HCT116 and LoVo. A combination of lovastatin (>3.75 mu M) and 2-deoxy-D-glucose (>1.25 mM) synergistically reduced cell viability, arrested cells in the G(2)/M phase, and induced apoptosis. The combined treatment also reduced cellular oxygen consumption and extracellular acidification rate, resulting in decreased production of ATP and lower steady-state ATP levels. Energy depletion markedly activated AMPK, inhibited mTOR and RAS signaling pathways, eventually inducing autophagy, the cellular pro-survival process under metabolic stress, whereas inhibition of autophagy by chloroquine (6.25 mu M) enhanced the cytotoxic effect of the combination of lovastatin and 2-deoxy-D-glucose. These in vitro experiment results were reproduced in a nude mouse xenograft model of HCT116 cells. Our findings suggest that concurrently targeting glycolysis, oxidative phosphorylation, and autophagy may be a promising regimen for the management of RAS-driven colorectal cancers.	[Huang, Xiao-ming; Huang, Jia-jun; Du, Jing-jing; Zhang, Na; Long, Ze; Yang, You; Zhong, Fang-fang; Zheng, Bo-wen; Shen, Yun-fu; Huang, Zhe; Qin, Xiang; Chen, Jun-he; Lin, Qian-yu; Lin, Wan-jun; Ma, Wen-zhe] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China		Ma, WZ (corresponding author), Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China.	wzma@must.edu.mo	/AAS-7015-2021		Science and Technology Development Fund, Macau SAR, China [0036/2020/A1, 0013/2019/A1, 0039/2020/A]	This work was funded by the Science and Technology Development Fund, Macau SAR, China (File no. 0036/2020/A1, 0013/2019/A1 and 0039/2020/A).	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Sin.	NOV	2021	42	11					1875	1887		10.1038/s41401-021-00612-9		FEB 2021	13	Chemistry, Multidisciplinary; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Pharmacology & Pharmacy	WQ9BZ	WOS:000619696700001	33608672				2022-04-25	
J	Zhou, CX; Gu, J; Zhang, G; Dong, D; Yang, QY; Chen, MB; Xu, DF				Zhou, Chunxian; Gu, Jun; Zhang, Gang; Dong, Da; Yang, Qunying; Chen, Min-Bin; Xu, Dongfeng			AMPK-autophagy inhibition sensitizes icaritin-induced anti-colorectal cancer cell activity	ONCOTARGET			English	Article						colorectal cancer; icaritin; autophagy; AMPK; chemosensitization	ACTIVATED PROTEIN-KINASE; SMALL-MOLECULE ACTIVATOR; COMPOUND 13; PRECLINICAL EVALUATION; THERAPEUTIC TARGET; ANTICANCER AGENT; PHOSPHORYLATION; GROWTH; PATHWAY; DEATH	The current research studied the potential effect of autophagy on icaritin-induced anti-colorectal cancer (CRC) cell activity. Treatment of icaritin in both primary and established (HT-29) CRC cells induced feedback activation of autophagy, evidenced by p62 degradation, Beclin-1 and autophagy-related gene-5 (ATG-5) upregulation, as well as light chain 3B (LC3B)-GFP puncta formation. Pharmacological inhibiting of autophagy dramatically potentiated icaritin-induced CRC cell death and apoptosis. Meanwhile, shRNA-mediated knockdown of Beclin-1 or ATG-5 also sensitized icaritin-induced CRC cell death and apoptosis. Icaritin activated AMP-activated protein kinase (AMPK) signaling in CRC cells, functioning as the upstream signaling for autophagy activation. shRNA/siRNA-mediated knockdown of AMPKa1inhibited icaritin-induced autophagy activation, but exacerbated CRC cell death. On the other hand, the AMPK activator compound 13 (C13) or the autophagy activator MHY1485 attenuated icaritin-induced cytotoxicity. In nude mice, icaritin (oral administration)-induced HT-29 tumor growth inhibition was potentiated when combined with AMPKa1 shRNA knockdown in tumors. We conclude that feedback activation of AMPK-autophagy pathway could be a primary resistance factor of icaritin.	[Zhou, Chunxian; Zhang, Gang; Dong, Da; Yang, Qunying; Xu, Dongfeng] Nantong Univ, Wujiang Hosp, Dept Intervent Radiol, Suzhou, Peoples R China; [Gu, Jun] Soochow Univ, Affiliated Hosp 2, Dept Orthoped, Suzhou, Peoples R China; [Chen, Min-Bin] Jiangsu Univ, Kunshan Peoples Hosp 1, Dept Oncol, Kunshan 215300, Peoples R China		Xu, DF (corresponding author), Nantong Univ, Wujiang Hosp, Dept Intervent Radiol, Suzhou, Peoples R China.; Chen, MB (corresponding author), Jiangsu Univ, Kunshan Peoples Hosp 1, Dept Oncol, Kunshan 215300, Peoples R China.	cmb1981@163.com; drxudongfeng6@126.com			WuJiang Science Bureau; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472786]; Foundation of tumor clinical and basic research team of Kunshan First People's Hospital [KYC005]	The study was supported by WuJiang Science Bureau and the National Natural Science Foundation of China (81472786), the Foundation of tumor clinical and basic research team of Kunshan First People's Hospital (KYC005).	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J	Ferro, F; Servais, S; Besson, P; Roger, S; Dumas, JF; Brisson, L				Ferro, Fabio; Servais, Stephane; Besson, Pierre; Roger, Sebastien; Dumas, Jean-Francois; Brisson, Lucie			Autophagy and mitophagy in cancer metabolic remodelling	SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY			English	Review						Cancer metabolism; Autophagy; Mitophagy; ROS; Mitochondria; Ion channel	HYPOXIA-INDUCED AUTOPHAGY; TUMOR-SUPPRESSOR GENE; CELL-DEATH; OXIDATIVE STRESS; MITOCHONDRIAL DYSFUNCTION; HEPATOCELLULAR-CARCINOMA; REGULATE AUTOPHAGY; COLORECTAL-CANCER; LIPID-METABOLISM; CA2+ TRANSFER	Metabolic reprogramming in tumours is now recognized as a hallmark of cancer, participating both in tumour growth and cancer progression. Cancer cells develop global metabolic adaptations allowing them to survive in the low oxygen and nutrient tumour microenvironment. Among these metabolic adaptations, cancer cells use glycolysis but also mitochondrial oxidations to produce ATP and building blocks needed for their high proliferation rate. Another particular adaptation of cancer cell metabolism is the use of autophagy and specific forms of autophagy like mitophagy to recycle intracellular components in condition of metabolic stress or during anticancer treatments. The plasticity of cancer cell metabolism is a major limitation of anticancer treatments and could participate to therapy resistances. The aim of this review is to report recent advances in the understanding of the relationship between tumour metabolism and autophagy/mitophagy in order to propose new therapeutic strategies.	[Ferro, Fabio; Servais, Stephane; Besson, Pierre; Dumas, Jean-Francois; Brisson, Lucie] Univ Tours, INSERM, UMR1069, Nutr Croissance & Canc, Tours, France; [Roger, Sebastien] Univ Tours, EA4245, Transplantat Immunol & Inflammat, Tours, France		Brisson, L (corresponding author), Univ Tours, INSERM, UMR 1069, 10 Blvd Tonnelle, F-37032 Tours, France.	lucie.brisson@univ-tours.fr	Dumas, Jean-François/S-7486-2017; Servais, Stephane/Q-6057-2017; Dumas, Jean-François/AAN-5035-2020; Brisson, Lucie/R-1179-2016	Dumas, Jean-François/0000-0002-2293-6606; Servais, Stephane/0000-0002-3127-9679; Dumas, Jean-François/0000-0002-2293-6606; Brisson, Lucie/0000-0001-7811-1382	InsermInstitut National de la Sante et de la Recherche Medicale (Inserm)European Commission; Ligue Nationale Contre le Cancer -Inter-region Grand-Ouest; Fondation ARC; Canceropole Grand-Ouest	We thank all our colleagues from the Universite de Tours-Inserm UMR1069 for all constructive discussion and Ms. Catherine Le Roy for secretary and administrative assistance. The work performed at the Universite de Tours-Inserm UMR1069 was supported by the Inserm, the "Ligue Nationale Contre le Cancer -Inter-region Grand-Ouest", the Fondation ARC and the "Canceropole Grand-Ouest".; Finally, we wish to apologize to all researchers whose relevant works, owing to the limited length of this article format, could not be cited in this review.	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Cell Dev. Biol.	FEB	2020	98				SI		129	138		10.1016/j.semcdb.2019.05.029			10	Cell Biology; Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Developmental Biology	KD5XE	WOS:000507938200015	31154012	Green Submitted, Bronze			2022-04-25	
J	Parashar, K; Sood, S; Mehaidli, A; Curran, C; Vegh, C; Nguyen, C; Pignanelli, C; Wu, JZ; Liang, G; Wang, Y; Pandey, S				Parashar, Krishan; Sood, Siddhartha; Mehaidli, Ali; Curran, Colin; Vegh, Caleb; Nguyen, Christopher; Pignanelli, Christopher; Wu, Jianzhang; Liang, Guang; Wang, Yi; Pandey, Siyaram			Evaluating the Anti-cancer Efficacy of a Synthetic Curcumin Analog on Human Melanoma Cells and Its Interaction with Standard Chemotherapeutics	MOLECULES			English	Article						melanoma; curcumin analog; apoptosis; oxidative stress; drug-drug interaction; tamoxifen; taxol; cisplatin	MITOCHONDRIAL DYSFUNCTION; PROOXIDANT ACTIVITY; APOPTOSIS PATHWAYS; CANCER-CELLS; COMPLEX-I; MECHANISMS; INDUCTION; TAMOXIFEN; AUTOPHAGY; SURVIVAL	Melanoma is the leading cause of skin-cancer related deaths in North America. Metastatic melanoma is difficult to treat and chemotherapies have limited success. Furthermore, chemotherapies lead to toxic side effects due to nonselective targeting of normal cells. Curcumin is a natural product of Curcuma longa (turmeric) and has been shown to possess anti-cancer activity. However, due to its poor bioavailability and stability, natural curcumin is not an effective cancer treatment. We tested synthetic analogs of curcumin that are more stable. One of these derivatives, Compound A, has shown significant anti-cancer efficacy in colon, leukemia, and triple-negative inflammatory breast cancer cells. However, the effects of Compound A against melanoma cells have not been studied before. In this study, for the first time, we demonstrated the efficacy of Compound A for the selective induction of apoptosis in melanoma cells and its interaction with tamoxifen, taxol, and cisplatin. We found that Compound A induced apoptosis selectively in human melanoma cells by increasing oxidative stress. The anti-cancer activity of Compound A was enhanced when combined with tamoxifen and the combination treatment did not result in significant toxicity to noncancerous cells. Additionally, Compound A did not interact negatively with the anti-cancer activity of taxol and cisplatin. These results indicate that Compound A could be developed as a selective and effective melanoma treatment either alone or in combination with other non-toxic agents like tamoxifen.	[Parashar, Krishan; Sood, Siddhartha; Mehaidli, Ali; Curran, Colin; Vegh, Caleb; Nguyen, Christopher; Pignanelli, Christopher; Pandey, Siyaram] Univ Windsor, Dept Chem & Biochem, 401 Sunset Ave, Windsor, ON N9B 3P4, Canada; [Wu, Jianzhang; Liang, Guang; Wang, Yi] Whenzhou Med Univ, Chem Biol Res Ctr, Sch Pharmaceut Sci, Wenzhou 325035, Peoples R China		Pandey, S (corresponding author), Univ Windsor, Dept Chem & Biochem, 401 Sunset Ave, Windsor, ON N9B 3P4, Canada.	spandey@uwindsor.ca	Pandey, Siyaram/AAI-5491-2020	Pignanelli, Christopher/0000-0001-7120-4818; Sood, Siddhartha/0000-0003-3531-5961	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472307]	Funding for this work was by generous donations by the Windsor Mold Group (Windsor, Ontario), Lotte and John Hecht Foundation, and Natural Science and Engineering Council of Canada. A grant from the National Natural Science Foundation of China (81472307) was used to fund the synthesis of each analog.	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J	Mihanfar, A; Darband, SG; Sadighparvar, S; Kaviani, M; Mirza-Aghazadeh-Attari, M; Yousefi, B; Majidinia, M				Mihanfar, Ainaz; Darband, Saber Ghazizadeh; Sadighparvar, Shirin; Kaviani, Mojtaba; Mirza-Aghazadeh-Attari, Mohammad; Yousefi, Bahman; Majidinia, Maryam			In vitro and in vivo anticancer effects of syringic acid on colorectal cancer: Possible mechanistic view	CHEMICO-BIOLOGICAL INTERACTIONS			English	Article						Colorectal cancer; Syringic acid; Proliferation; Apoptosis; Autophagy	CAFFEIC ACID; CELLS; PROLIFERATION; AUTOPHAGY; BREAST; GROWTH; ESTER	This study aimed to evaluate the in vitro effects of syringic acid on human colorectal cancer cells (SW-480) and the effect of orally administered syringic acid on in vivo models of colorectal cancer induced in rats by administration of 1,2-dimethylhydrazine (DMH). In vitro effects of syringic acid treatment on human colorectal cancer SW-480 cell lines were assessed by performing cell proliferation assay (MTT and Trypan Blue staining), apoptosis assays (TUNEL assay, Annexin-V/PI flowcytometry and lactate dehydrogenase release assay), measuring reactive oxygen species (ROS), antioxidant enzymes and DNA damage, and evaluating protein levels of proliferative genes, and autophagy markers. In vitro anti-cancer roles of syringic acid were studied in rats with DMH-induced colorectal cancer cells. The effect of orally administered syringic acid (50 mg/kg) on tumor growth and incidence was studied in four groups (n = 6) of animals injected with DMH and treated for 15 weeks. Syringic acid treatment resulted in a significant dose-dependent inhibition of cellular proliferation, induction of apoptosis through increasing cellular ROS and DNA damage levels, as well as downregulating major proliferative genes. In vivo, treatment of rats with syringic acid demonstrated a statistically significant tumor volume and incidence reduction when compared to the control. This is the first study demonstrating an in vivo growth inhibitory effect of orally administered syringic acid on colorectal tumors in rats.	[Mihanfar, Ainaz] Urmia Univ Med Sci, Fac Med, Dept Biochem, Orumiyeh, Iran; [Darband, Saber Ghazizadeh; Sadighparvar, Shirin] Urmia Univ Med Sci, Neurophysiol Res Ctr, Orumiyeh, Iran; [Kaviani, Mojtaba] Acadia Univ, Sch Nutr & Dietet, Wolfville, NS B4P 2R6, Canada; [Mirza-Aghazadeh-Attari, Mohammad] Tabriz Univ Med Sci, Student Res Comm, Tabriz, Iran; [Mirza-Aghazadeh-Attari, Mohammad] Tabriz Univ Med Sci, Aging Res Inst, Tabriz, Iran; [Yousefi, Bahman] Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz, Iran; [Majidinia, Maryam] Urmia Univ Med Sci, Solid Tumor Res Ctr, Orjhans St,Resalat Blvd, Orumiyeh, Iran		Majidinia, M (corresponding author), Urmia Univ Med Sci, Solid Tumor Res Ctr, Orjhans St,Resalat Blvd, Orumiyeh, Iran.	majidinia.m@umsu.ac.ir		Mirza-Aghazadeh-Attari, Mohammad/0000-0001-7927-6912	Urmia University of Medical Sciences [273]	This study was funded by Urmia University of Medical Sciences (grant number: 273).	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Interact.	MAR 1	2021	337								109337	10.1016/j.cbi.2020.109337		FEB 2021	11	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology	QL2OE	WOS:000620918900001	33548266				2022-04-25	
J	Ye, YQ; Zhang, PJ; Qian, YH; Yin, BX; Yan, MJ				Ye, Yongqi; Zhang, Pengju; Qian, Yuhang; Yin, Baoxin; Yan, Meijuan			The Effect of Pyrroloquinoline Quinone on the Expression of WISP1 in Traumatic Brain Injury	STEM CELLS INTERNATIONAL			English	Article							SIGNALING PATHWAY PROTEIN-1; INDUCED CARDIOMYOCYTE DEATH; BETA-CATENIN; ALZHEIMERS-DISEASE; GROWTH-FACTOR; AUTOPHAGY; CELLS; SURVIVAL; PQQ; NEUROPROTECTION	WISP1, as a member of the CCN4 protein family, has cell protective effects of promoting cell proliferation and inhibiting cell apoptosis. Although some studies have confirmed that WISP1 is concerned with colon cancer and lung cancer, there is little report about the influence of WISP1 in traumatic brain injury. Here, we found that the expression of WISP1 mRNA and protein decreased at 3 d and then increased at 5 d after traumatic brain injury (TBI). Meanwhile, immunofluorescence demonstrated that there was little colocation of WISP1 with GFAP, Iba1, and WISP1 colocalized with NeuN partly. WISP1 colocalized with LC3, but there was little of colocation about WISP1 with cleaved caspase-3. Subsequent study displayed that the expression of beta-catenin protein was identical to that of WISP1 after TBI. WISP1 was mainly located in cytoplasm of PC12 or SHSY5Y cells. Compared with the negative control group, WISP1 expression reduced obviously in SHSY5Y cells transfected with WISP1 si-RNA. CCK-8 assay showed that pyrroloquinoline quinone (PQQ) had little influence on viability of PC12 and SHSY5Y cells. These results suggested that WISP1 played a protective role after traumatic brain injury in rats, and this effect might be relative to autophagy caused by traumatic brain injury.	[Ye, Yongqi; Zhang, Pengju; Qian, Yuhang; Yin, Baoxin; Yan, Meijuan] Nantong Univ, Jiangsu Key Lab Neuroregenerat, 19 Qixiu Rd, Nantong 226001, Peoples R China		Yan, MJ (corresponding author), Nantong Univ, Jiangsu Key Lab Neuroregenerat, 19 Qixiu Rd, Nantong 226001, Peoples R China.	ymz@ntu.edu.cn	yan, mei/AAA-1379-2022		National Natural Scientific Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31370803]; Application Study Program of Nantong City [BK2013004]; Early Pre-research Program of Nantong University [10ZY013]; Doctoral Program of Nantong University [12B035]	This work was supported by the National Natural Scientific Foundation of China (31370803), Application Study Program of Nantong City (BK2013004), Early Pre-research Program of Nantong University (10ZY013), and Doctoral Program of Nantong University (12B035).	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Med.	NOV	2020	17	06					469	490		10.2217/pme-2020-0103		OCT 2020	22	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	OI1IN	WOS:000577575100001	33052780				2022-04-25	
J	Gil, J; Ramsey, D; Pawlowski, P; Szmida, E; Leszczynski, P; Bebenek, M; Sasiadek, MM				Gil, J.; Ramsey, D.; Pawlowski, P.; Szmida, E.; Leszczynski, P.; Bebenek, M.; Sasiadek, M. M.			INTERDEPENDENCE BETWEEN AN EXPRESSION OF THE ATG9A GENE AND THE BAX GENE IN COLORECTAL CANCER	JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS			English	Article						autophagy; apoptosis; colorectal cancer; relative expression; ATG genes	AUTOPHAGY	Despite great progress in colorectal cancer (CRC) prevention, early recognition and treatment, a high frequency of morbidity and mortality of CRC patients is still observed even in developed countries. Molecular characterization of this tumor becomes a standard procedure allowing for application of personalized therapy. However, searching for new biomarkers and for new individual therapeutic strategies is increasingly desirable. In this study on molecular background of CRC, we focused on analyses of mRNA levels of autophagy gene ATG9A and pro-apoptotic gene BAX. Genes involved in autophagy, that is the catabolic and conservative cellular process, have been revealed as a promising new cancer biomarker as well as anti-cancer target. Under normal circumstances autophagy occurs at a low, basal level in most human cells, however in cancer cells its expression varies from down- to upregulation. Despite the fact that the complex link between autophagy and apoptosis is well documented, these interrelations have not yet been fully uncovered. The relative expression of mRNA values of ATG9A and BAX genes in colorectal cancer samples vs normal adjacent tissues was assessed by Real-time PCR with Universal Probe Library. The results of our study revealed a statistically significant correlation between the expression of BAX and ATG9A genes, showing that in CRC a higher expression of BAX gene is connected with lower expression of ATG9A.	[Gil, J.; Pawlowski, P.; Szmida, E.; Sasiadek, M. M.] Wroclaw Med Univ, Dept Genet, Ul Marcinkowskiego 1, PL-50368 Wroclaw, Poland; [Ramsey, D.] Wroclaw Univ kchnol, Dept Operat Res, Wroclaw, Poland; [Leszczynski, P.] Wroclaw Med Univ, Dept Biol & Med Parasitol, Wroclaw, Poland; [Bebenek, M.] Lower Silesian Oncol Ctr, Dept Surg Oncol 1, Wroclaw, Poland		Gil, J (corresponding author), Wroclaw Med Univ, Dept Genet, Ul Marcinkowskiego 1, PL-50368 Wroclaw, Poland.	justyna.gil@umed.wroc.pl	/L-5618-2019	/0000-0003-0991-7686; Sasiadek, Maria/0000-0002-7599-7074; Leszczynski, Przemyslaw/0000-0002-4181-4997; Szmida, Elzbieta/0000-0003-3108-0165; Bebenek, Marek/0000-0001-7716-5960	National Science Centre (Poland) [DEC-2012/07/D/NZ5/04305]	This work was financed from the funds of the National Science Centre (Poland), decision number DEC-2012/07/D/NZ5/04305.	Banerjee R, 2010, TRENDS NEUROSCI, V33, P541, DOI 10.1016/j.tins.2010.09.001; Gil J, 2017, MED ONCOL, V34, DOI 10.1007/s12032-016-0869-y; Gil J, 2016, BIOMARK MED, V10, P1081, DOI 10.2217/bmm-2016-0083; Gump JM, 2011, TRENDS CELL BIOL, V21, P387, DOI 10.1016/j.tcb.2011.03.007; Meddens CA, 2016, GENOME BIOL, V17, DOI 10.1186/s13059-016-1100-3; Rahim SAA, 2017, BRIT J CANCER, V117, P813, DOI 10.1038/bjc.2017.263; Reggiori F, 2012, J CELL BIOL, V198, P151, DOI 10.1083/jcb.201206119; Saitoh T, 2009, P NATL ACAD SCI USA, V106, P20842, DOI 10.1073/pnas.0911267106; Siegel R, 2014, CA-CANCER J CLIN, V64, P104, DOI 10.3322/caac.21220; Staudt C, 2016, BIOCHEM BIOPH RES CO, V479, P404, DOI 10.1016/j.bbrc.2016.09.097; Staudt C, 2016, BBA-MOL CELL RES, V1863, P2299, DOI 10.1016/j.bbamcr.2016.06.007; Yamamoto H, 2012, J CELL BIOL, V198, P219, DOI 10.1083/jcb.201202061	12	1	1	0	2	BIOLIFE SAS	SILVA MARINA (TE)	VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY	0393-974X	1724-6083		J BIOL REG HOMEOS AG	J. Biol. Regul. Homeost. Agents	JAN-FEB	2019	33	1					183	185					3	Endocrinology & Metabolism; Immunology; Medicine, Research & Experimental; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Endocrinology & Metabolism; Immunology; Research & Experimental Medicine; Physiology	HT6TS	WOS:000464697500025	30761869				2022-04-25	
J	Abdel-Rafei, MK; Thabet, NM; Maksoud, MIAA; Abd Elkodous, M; Kawamura, G; Matsuda, A; Ashour, AH; El-Batal, AI; El-Sayyad, GS				Abdel-Rafei, Mohamed K.; Thabet, Noura M.; Abdel Maksoud, M. I. A.; Abd Elkodous, M.; Kawamura, Go; Matsuda, Atsunori; Ashour, A. H.; El-Batal, Ahmed I.; El-Sayyad, Gharieb S.			Influence of Ce3+ Substitution on Antimicrobial and Antibiofilm Properties of ZnCexFe2-xO4 Nanoparticles (X=0.0, 0.02, 0.04, 0.06, and 0.08) Conjugated with Ebselen and Its Role Subsidised with gamma-Radiation in Mitigating Human TNBC and Colorectal Adenocarcinoma Proliferation In Vitro	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						MDA-MB-231; HT-29; ebselen; cerium; ERK1; 2; STAT-6; IL-4; STAT-1; antimicrobial activity	CERIUM OXIDE NANOPARTICLES; MAGNETIC-PROPERTIES; FERRITE NANOPARTICLES; CELL-CYCLE; DIELECTRIC-PROPERTIES; ELECTRICAL-PROPERTIES; PATHOGENIC BACTERIA; CATION DISTRIBUTION; CEO2 NANOPARTICLES; IONIC-STRENGTH	Cancers are a major challenge to health worldwide. Spinel ferrites have attracted attention due to their broad theranostic applications. This study aimed at investigating the antimicrobial, antibiofilm, and anticancer activities of ebselen (Eb) and cerium-nanoparticles (Ce-NPs) in the form of ZnCexFe2-XO4 on human breast and colon cancer cell lines. Bioassays of the cytotoxic concentrations of Eb and ZnCexFe2-XO4, oxidative stress and inflammatory milieu, autophagy, apoptosis, related signalling effectors, the distribution of cells through the cell-cycle phases, and the percentage of cells with apoptosis were evaluated in cancer cell lines. Additionally, the antimicrobial and antibiofilm potential have been investigated against different pathogenic microbes. The ZOI, and MIC results indicated that ZnCexFe2-XO4; X = 0.06 specimen reduced the activity of a wide range of bacteria and unicellular fungi at low concentration including P. aeruginosa (9.5 mm; 6.250 mu g/mL), S. aureus (13.2 mm; 0.390 mu g/mL), and Candida albicans (13.5 mm; 0.195 mu g/mL). Reaction mechanism determination indicated that after ZnCexFe2-xO4; X = 0.06 treatment, morphological differences in S. aureus were apparent with complete lysis of bacterial cells, a concomitant decrease in the viable number, and the growth of biofilm was inhibited. The combination of Eb with ZFO or ZnCexFe2-XO4 with gamma-radiation exposure showed marked anti-proliferative efficacy in both cell lines, through modulating the oxidant/antioxidant machinery imbalance, restoring the fine-tuning of redox status, and promoting an anti-inflammatory milieu to prevent cancer progression, which may be a valuable therapeutic approach to cancer therapy and as a promising antimicrobial agent to reduce the pathogenic potential of the invading microbes.	[Abdel-Rafei, Mohamed K.; Thabet, Noura M.] Natl Ctr Radiat Res & Technol NCRRT, Egyptian Atom Energy Author EAEA, Radiat Biol Dept, Cairo 11787, Egypt; [Abdel Maksoud, M. I. A.; Ashour, A. H.] Natl Ctr Radiat Res & Technol NCRRT, Egyptian Atom Energy Author EAEA, Mat Sci Lab, Cairo 11787, Egypt; [Abd Elkodous, M.; Kawamura, Go; Matsuda, Atsunori] Toyohashi Univ Technol, Dept Elect & Elect Informat Engn, 1-1 Hibarigaoka,Tempaku Cho, Toyohashi, Aichi 441, Japan; [El-Batal, Ahmed I.; El-Sayyad, Gharieb S.] Natl Ctr Radiat Res & Technol NCRRT, Egyptian Atom Energy Author EAEA, Drug Microbiol Lab, Drug Radiat Res Dept, Cairo 11787, Egypt		Thabet, NM (corresponding author), Natl Ctr Radiat Res & Technol NCRRT, Egyptian Atom Energy Author EAEA, Radiat Biol Dept, Cairo 11787, Egypt.; Matsuda, A (corresponding author), Toyohashi Univ Technol, Dept Elect & Elect Informat Engn, 1-1 Hibarigaoka,Tempaku Cho, Toyohashi, Aichi 441, Japan.	mohamed.marawan2011@yahoo.com; noura_magdy@hotmail.com; muhamadmqsod@gmail.com; mohamed.hamada.abdlekodous.xi@tut.jp; kawamura.go.km@tut.jp; matsuda@ee.tut.ac.jp; ashourvip3@hotmail.com; aelbatal2020@gmail.com; Gharieb.S.Elsayyad@eaea.org.eg	Thabet, Noura Magdy/P-8402-2015; Abdel Maksoud, Muhammad Ibrahim Ahmed/S-7676-2018	Thabet, Noura Magdy/0000-0003-0073-7347; Abdel Maksoud, Muhammad Ibrahim Ahmed/0000-0001-7708-9646; Abd Elkodous, Mohamed/0000-0002-9408-9178; matsuda, atsunori/0000-0002-6493-1205	Japan Society for Promotion of Science (JSPS) KAKENHIMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [18H03841, 21K18823]	This study was partly funded by Japan Society for Promotion of Science (JSPS) KAKENHI Grant No. 18H03841 and No. 21K18823.	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J. Mol. Sci.	SEP	2021	22	18							10171	10.3390/ijms221810171			40	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	UW6JN	WOS:000700259700001	34576334	Green Published, gold			2022-04-25	
J	Zhou, HY; Yuan, M; Yu, QF; Zhou, XY; Min, WP; Gao, D				Zhou, Huangyan; Yuan, Min; Yu, Qiongfang; Zhou, Xiaoyan; Min, Weiping; Gao, Dian			Autophagy regulation and its role in gastric cancer and colorectal cancer	CANCER BIOMARKERS			English	Review						Autophagy; gastric cancer; colorectal cancer	TUMOR-SUPPRESSOR; FRAMESHIFT MUTATION; THERAPEUTIC TARGET; HUMAN HEALTH; IN-VITRO; EXPRESSION; BECLIN-1; PATHWAYS; KRAS; RAS	BACKGROUND: Autophagy is associated with the occurrence, development, cellular adaptation, progression, treatment and prognosis of gastric cancer (GC) and colorectal cancer (CRC). The effect of autophagy in these two cancers has attracted our attention. OBJECTIVE: The aim of this study was to describe the functional and regulatory mechanisms associated with autophagy in GC and CRC. METHODS: We reviewed recent publications describing the role of autophagy in GC and CRC, including the functional characteristics, clinical significance and regulatory mechanisms. RESULTS: Autophagy plays context-dependent dual roles in the development and progression of GC and CRC. It can either promote tumor growth and cell survival or can contribute to tumor suppression and promote cell death. Both of these effects employ complex regulatory networks, such as those mediated by p53, PI3K/Akt/mTOR, Ras and microRNA. Among the cellular process associated with these pathways, autophagy is a potential target for anti-tumor therapy. CONCLUSION: Autophagy is associated with both tumorigenic and protective effects in cancer. However, the role of autophagy in GC and CRC remains unclear. Although the translation of the basic science of autophagy into clinical practice is a long process, the modulation of autophagy as a potential therapeutic approach in GC and CRC merits further investigation.	[Zhou, Huangyan; Min, Weiping; Gao, Dian] Nanchang Univ, Coll Med, Dept Pathogen Biol & Immunol, 461 Bayi Rd, Nanchang 330006, Jiangxi, Peoples R China; [Zhou, Huangyan; Min, Weiping; Gao, Dian] Jiangxi Acad Med Sci, Nanchang, Jiangxi, Peoples R China; [Zhou, Huangyan; Min, Weiping; Gao, Dian] Nanchang Univ, Inst Immunotherapy, Nanchang, Jiangxi, Peoples R China; [Yuan, Min] Nanchang Univ, Affiliated Hosp 2, Dept Neurol, Nanchang, Jiangxi, Peoples R China; [Yu, Qiongfang] Nanchang Univ, Affiliated Hosp 2, Dept Gastroenterol & Hepatol, Nanchang, Jiangxi, Peoples R China; [Zhou, Xiaoyan] Nanchang Univ, Coll Med, Dept Pathophysiol, Nanchang, Jiangxi, Peoples R China		Gao, D (corresponding author), Nanchang Univ, Coll Med, Dept Pathogen Biol & Immunol, 461 Bayi Rd, Nanchang 330006, Jiangxi, Peoples R China.	gaodian@ncu.edu.cn	Yuan, Min/ABF-7560-2020	Yuan, Min/0000-0002-1190-5337; Gao, Dian/0000-0002-9391-1756	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31460696, 81460462, 81460126]; Technology Pedestal and Society Development Project of Jiangxi Province [20141BBG70040]; Foundation of Jiangxi Educational Committee [86283702]; Department of Health of Jiangxi Province [20155629]	The authors thank Dr. Wirnkar S. Jadwiga for his help in English language editing. This work is supported by grants from National Natural Science Foundation of China (No. 31460696, 81460462, 81460126), Technology Pedestal and Society Development Project of Jiangxi Province (No. 20141BBG70040), Foundation of Jiangxi Educational Committee (No. 86283702), Department of Health of Jiangxi Province (No. 20155629).	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J	Ryoo, IG; Choi, BH; Kwak, MK				Ryoo, In-geun; Choi, Bo-hyun; Kwak, Mi-Kyoung			Activation of NRF2 by p62 and proteasome reduction in sphere-forming breast carcinoma cells	ONCOTARGET			English	Article						mammospheres; cancer stem cell; resistance; NRF2; p62	CANCER STEM-CELLS; ANTIOXIDANT RESPONSE ELEMENT; TRANSCRIPTION FACTOR NRF2; IN-VITRO PROPAGATION; INITIATING CELLS; SELF-RENEWAL; SUBUNIT EXPRESSION; OXIDATIVE STRESS; AUTOPHAGY; KEAP1	Cancer stem cells (CSCs) express high levels of drug efflux transporters and antioxidant genes, and are therefore believed to be responsible for cancer recurrence following chemo/radiotherapy intervention. In this study, we investigated the role of NF-E2-related factor 2 (NRF2), a master regulator of antioxidant gene expression, in the growth and stress resistance of CSC-enriched mammosphere. The MCF7 mammospheres expressed significantly higher levels of the NRF2 protein and target gene expression compared to the monolayer. As underlying mechanisms, we observed that proteolytic activity and expression of the proteasome catalytic subunits were decreased in the mammospheres. Additionally, mammospheres retained a high level of p62 and the silencing of p62 was observed to attenuate NRF2 activation. NRF2 increase was confirmed in sphere-cultures of the colon and ovarian cancer cells. The functional implication of NRF2 was demonstrated in NRF2-knockdown mammospheres. NRF2-silenced mammospheres demonstrated increased cell death and retarded sphere growth as a result of target gene repression. Moreover, unlike the control mammospheres, NRF2-knockdown mammospheres did not develop anticancer drug resistance. Collectively, these results indicated that altered proteasome function and p62 expression caused NRF2 activation in CSC-enriched mammospheres. In addition, NRF2 appeared to play a role in CSC survival and anticancer drug resistance.	[Ryoo, In-geun; Choi, Bo-hyun; Kwak, Mi-Kyoung] Catholic Univ Korea, Coll Pharm, Bucheon, Gyeonggi Do, South Korea		Kwak, MK (corresponding author), Catholic Univ Korea, Coll Pharm, Bucheon, Gyeonggi Do, South Korea.	mkwak@catholic.ac.kr			National Research Foundation (NRF) - Ministry of Science, ICT & Future Planning [NRF-2013R1A2A2A01015497]	This study was financially supported by the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2013R1A2A2A01015497).	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J	Ren, YC; Yuan, BC; Hou, SH; Sui, YL; Yang, TH; Lv, ML; Zhou, YL; Yu, H; Li, S; Peng, HS; Chang, ND; Liu, Y				Ren, Yachao; Yuan, Bingchuan; Hou, Shenghua; Sui, Yilei; Yang, Tinghui; Lv, Meilin; Zhou, Yulong; Yu, Hui; Li, Sen; Peng, Haisheng; Chang, Naidan; Liu, Yang			Delivery of RGD-modified liposome as a targeted colorectal carcinoma therapy and its autophagy mechanism	JOURNAL OF DRUG TARGETING			English	Article						RGD peptide; liposomes; colorectal drug targeting; targeting mechanism; autophagy	DRUG-DELIVERY; ALPHA-V-BETA-3 INTEGRIN; NANOPARTICLES; CANCER; SYSTEM; EXPRESSION; PEPTIDE; CELLS	Liposomes are among the most extensively applied drug carriers due to their excellent biocompatibility, controllable size and ease of modification. In the present study, we prepared untargeted liposomes (LP) and targeting liposomes modified with Arg-Gly-Asp (RGD-LP), and Doxorubicin Hydrochloride (DOX) or fluorescent probe was loaded. RGD-LP/DOX was identified to be uniformly spherical in size 131.2 +/- 2.7 nm. Based on flow cytometry analysis and the confocal laser scanning microscopy, RGD-LP had a higher uptake into HRT-18 colorectal cancer cells than LP. Further, in vivo imaging study further suggested that RGD-LP could significantly increase the liposome accumulation in the tumour tissues of the mice bearing subcutaneous tumours. By investigating the targeting mechanism of RGD-LP, we found that they entered the cell via macropinocytosis. When loaded with DOX, RGD-LP exerted stronger tumour growth inhibitory activity against tumours of colorectal carcinoma compared to LP. Moreover, RGD-LP induced autophagy. Therefore, RGD-LP have the potential to be applied as a targeted colorectal carcinoma therapy.	[Ren, Yachao; Yuan, Bingchuan; Hou, Shenghua; Sui, Yilei; Yang, Tinghui; Lv, Meilin; Yu, Hui; Li, Sen; Peng, Haisheng; Chang, Naidan] Harbin Med Univ Daqing, Dept Pharm, Daqing 163319, Peoples R China; [Zhou, Yulong] Heilongjiang Bayi Agr Univ, Coll Anim Sci & Technol, Daqing, Peoples R China; [Liu, Yang] Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China		Peng, HS; Chang, ND (corresponding author), Harbin Med Univ Daqing, Dept Pharm, Daqing 163319, Peoples R China.; Liu, Y (corresponding author), Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China.	fisher1688@163.com; changnaidan@126.com; liuyang8016@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81703426]; Natural Science Foundation of Heilongjiang ProvinceNatural Science Foundation of Heilongjiang Province [LH2019H010, H2018018]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2019M651312]; Heilongjiang Postdoctoral Fund [LBH-Z18106]; Health Commission of Heilongjiang Province [2017-170]; Mentor Found of Daqing campus, Harbin Medical University [XQJJ2016003]; Innovation and Entrepreneurship Programme for College Students in Heilongjiang Province [201910226137]; Key research and development and promotion projects of Henan Province [192102310154]; Innovation and entrepreneurship training program of Zhengzhou University [202010459148]	This work was supported by National Natural Science Foundation of China (81703426); Natural Science Foundation of Heilongjiang Province (LH2019H010); Natural Science Foundation of Heilongjiang Province (H2018018); China Postdoctoral Science Foundation (2019M651312); Heilongjiang Postdoctoral Fund (LBH-Z18106); Health Commission of Heilongjiang Province (2017-170); the Mentor Found (XQJJ2016003) of Daqing campus, Harbin Medical University; and Innovation and Entrepreneurship Programme for College Students in Heilongjiang Province (201910226137); Key research and development and promotion projects of Henan Province (192102310154); Innovation and entrepreneurship training program of Zhengzhou University (202010459148).	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Drug Target.	SEP 14	2021	29	8					863	874		10.1080/1061186X.2021.1882469		FEB 2021	12	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	UB2PH	WOS:000618265600001	33507113				2022-04-25	
J	Lee, J; Zhou, W; Na, M; Oh, S				Lee, Jaehoo; Zhou, Wei; Na, MinKyun; Oh, Sangtaek			Cytotoxic Activity of Aplykurodin A Isolated From Aplysia kurodai against AXIN1-Mutated Hepatocellular Carcinoma Cells by Promoting Oncogenic beta-Catenin Degradation	MARINE DRUGS			English	Article						hepatocellular carcinoma (HCC); aplykurodin A; Wnt; beta-catenin signaling; apoptosis; autophagy	DOWN-REGULATION; COLON-CANCER; SEA HARE; PROTEIN; TARGET; AUTOPHAGY; PATHWAY; COMPLEX; AXIN; PHOSPHORYLATION	Dysregulation of the Wnt/beta-catenin signaling pathway is involved in the development of human hepatocellular carcinoma and has thus emerged as a therapeutic target for this malignant tumor. In this study, we employed sensitive cell-based assays to identify aplykurodin A isolated from Aplysia kurodai as an antagonist of Wnt/beta-catenin signaling. Aplykurodin A inhibited beta-catenin responsive transcription, which was stimulated by a Wnt3a-conditioned medium or a glycogen synthase kinase 3 beta inhibitor by accelerating intracellular beta-catenin degradation. Aplykurodin A downregulated the level of oncogenic beta-catenin and decreased the expression of beta-catenin-dependent gene, leading to inhibition of human hepatoma Hep3B and SNU475 cell proliferation. Moreover, apoptosis and autophagy were elicited by aplykurodin A, as indicated by an increase the number of Annexin V-FITC-stained cells and the formation of microtubule-associated protein 1 light chain 3 puncta, respectively, in Hep3B and SNU475 cells. Our findings suggest that aplykurodin A provides a novel therapeutic strategy for human hepatocellular carcinoma via stimulation of oncogenic beta-catenin degradation.	[Lee, Jaehoo; Oh, Sangtaek] Kookmin Univ, Dept Bio & Fermentat Convergence Technol, BK21 PLUS Program, Seoul 136702, South Korea; [Zhou, Wei] Yanbian Univ, Coll Pharm, Yanji 133002, Peoples R China; [Na, MinKyun] Chungnam Natl Univ, Coll Pharm, Daejeon 34134, South Korea		Oh, S (corresponding author), Kookmin Univ, Dept Bio & Fermentat Convergence Technol, BK21 PLUS Program, Seoul 136702, South Korea.; Na, M (corresponding author), Chungnam Natl Univ, Coll Pharm, Daejeon 34134, South Korea.	wogn1208@gmail.com; zhouwei8452@163.com; mkna@cnu.ac.kr; ohsa@kookmin.ac.kr		Na, MinKyun/0000-0002-4865-6506	Basic Science Research Program through the National Research Foundation of Korea (NRF) grant - Korean Government [NRF-2018R1D1A1B07048208, NRF-2020R1A2B5B01002415]; World Class 300 Project R&D grant, Korea Small and Medium Business Administration (SMBA)	This work was supported by the Basic Science Research Program (NRF-2018R1D1A1B07048208; NRF-2020R1A2B5B01002415) through the National Research Foundation of Korea (NRF) grant funded by the Korean Government and by the World Class 300 Project R&D grant provided by the Korea Small and Medium Business Administration (SMBA).	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Drugs	APR	2020	18	4							210	10.3390/md18040210			12	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	LO8XP	WOS:000533909300031	32294900	Green Published, gold			2022-04-25	
J	Huang, YC; Hung, WC; Chen, WT; Yu, HS; Chai, CY				Huang, Ya-Chun; Hung, Wen-Chun; Chen, Wan-Tzu; Yu, Hsin-Su; Chai, Chee-Yin			Sodium arsenite-induced DAPK promoter hypermethylation and autophagy via ERK1/2 phosphorylation in human uroepithelial cells	CHEMICO-BIOLOGICAL INTERACTIONS			English	Article						Arsenite; SV-HUC-1 cells; ERK1/2; Autophagy; Beclin-1; DAPK	COLON-CANCER CELLS; ACTIVATED PROTEIN-KINASES; GROWTH-FACTOR RECEPTOR; DNA METHYLTRANSFERASE; GLIOMA-CELLS; DEATH; METHYLATION; TRIOXIDE; PATHWAY; INHIBITION	Arsenic compounds or arsenicals are well-known toxic and carcinogenic agents. The toxic effects of arsenic that are of most concern to humans are those that occur from chronic, low-level exposure, and are associated with various human malignancies, including skin, lung and bladder cancers. In addition, arsenic could induce cell death, including apoptosis or autophagy in malignant cells. Previously, we have demonstrated that arsenite can induce autophagy and death-associated protein kinase (DAPK) promoter hypermethylation in the SV-40 immortalized human uroepithelial cell line (SV-HUC-1). However, the underlying mechanism of arsenite-induced autophagy is still unclear. In the present study, we demonstrate that arsenite can activate the extracellular signaling-regulated protein kinase 1/2 (ERK1/2) signaling pathway after treatment in SV-HUC-1 cells by using immunocytochemistry and Western blotting. In addition, our results also show an increase of autophagosomes was produced in arsenite-treated SV-HUC-1 cells by using electron microscopy. We found that, by incrementally increasing the dosages, microtubule-associated protein light chain 3B (LOB) and Beclin-1 are important regulators for the formation of autophagosomes, in a dose-dependent manner. When the cells were pretreated with inhibitors 5-aza-CdR or U0126 for 24 h, the effect of arsenite on ERK1/2, LC3B, Beclin-1 and DAPK proteins expression is suppressed. Furthermore, Our results support the notion that arsenite can induce the ERK1/2 signaling pathway to stimulate autophagy and DAPK promoter hypermethylation in human uroepithelial SV-HUC-1 cells. These findings may contribute to a better understanding of the carcinogenesis of arsenite. (C) 2009 Elsevier Ireland Ltd. All rights reserved.	[Chen, Wan-Tzu; Chai, Chee-Yin] Kaohsiung Med Univ Hosp, Dept Pathol, Kaohsiung 807, Taiwan; [Yu, Hsin-Su] Kaohsiung Med Univ Hosp, Dept Dermatol, Kaohsiung 807, Taiwan; [Huang, Ya-Chun] Kaohsiung Med Univ, Coll Med, Grad Inst Med, Kaohsiung, Taiwan; [Huang, Ya-Chun; Chen, Wan-Tzu; Chai, Chee-Yin] Kaohsiung Med Univ, Coll Med, Dept Pathol, Kaohsiung, Taiwan; [Hung, Wen-Chun; Chai, Chee-Yin] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 80424, Taiwan; [Hung, Wen-Chun; Chai, Chee-Yin] Kaohsiung Med Univ, Natl Sun Yat Sen Univ, Joint Res Ctr, Kaohsiung, Taiwan; [Yu, Hsin-Su] Kaohsiung Med Univ, Coll Med, Dept Dermatol, Kaohsiung, Taiwan; [Yu, Hsin-Su; Chai, Chee-Yin] Kaohsiung Med Univ, Ctr Excellence Environm Med, Kaohsiung, Taiwan		Chai, CY (corresponding author), Kaohsiung Med Univ Hosp, Dept Pathol, 100 Tzyou 1st Rd, Kaohsiung 807, Taiwan.	cychai@kmu.edu.tw	Hung, Wen-Chun/F-4846-2011; Chai, Chee-Yin/D-5523-2009	Chai, Chee-Yin/0000-0003-0486-9742	National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, Kaohsiung, Taiwan; Center of Excellence for Environmental Medicine, Kaohsiung Medical University [KMU-EM-98-2-3]	This work was supported by a research grant from the National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, Kaohsiung, Taiwan and Center of Excellence for Environmental Medicine, Kaohsiung Medical University (KMU-EM-98-2-3).	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Interact.	OCT 7	2009	181	2					254	262		10.1016/j.cbi.2009.06.020			9	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology	499IO	WOS:000270212800013	19577553				2022-04-25	
J	Liang, D; Khoonkari, M; Avril, T; Chevet, E; Kruyt, FAE				Liang, Dong; Khoonkari, Mohammad; Avril, Tony; Chevet, Eric; Kruyt, Frank A. E.			The unfolded protein response as regulator of cancer stemness and differentiation: Mechanisms and implications for cancer therapy	BIOCHEMICAL PHARMACOLOGY			English	Review						Unfolded protein response; Cancer stem cells; Tumor formation; Therapy; PERK; IRE1	ENDOPLASMIC-RETICULUM STRESS; BREAST-CANCER; BONE-MARROW; CELLS; ACTIVATION; GSK2606414; DISCOVERY; AUTOPHAGY; SURVIVAL; TARGET	The unfolded protein response (UPR) is an adaptive mechanism that regulates protein and cellular homeostasis. Three endoplasmic reticulum (ER) membrane localized stress sensors, IRE1, PERK and ATF6, coordinate the UPR in order to maintain ER proteostasis and cell survival, or induce cell death when homeostasis cannot be restored. However, recent studies have identified alternative functions for the UPR in developmental biology processes and cell fate decisions under both normal and cancerous conditions. In cancer, increasing evidence points to-wards the involvement of the three UPR sensors in oncogenic reprogramming and the regulation of tumor cells endowed with stem cell properties, named cancer stem cells (CSCs), that are considered to be the most malignant cells in tumors. Here we review the reported roles and underlying molecular mechanisms of the three UPR sensors in regulating stemness and differentiation, particularly in solid tumor cells, processes that have a major impact on tumor aggressiveness. Mainly PERK and IRE1 branches of the UPR were found to regulate CSCs and tumor development and examples are provided for breast cancer, colon cancer and aggressive brain tumors, glioblastoma. Although the underlying mechanisms and interactions between the different UPR branches in regulating stemness in cancer need to be further elucidated, we propose that PERK and IRE1 targeted therapy could inhibit self-renewal of CSCs or induce differentiation that is predicted to have therapeutic benefit. For this, more specific UPR modulators need to be developed with favorable pharmacological properties that together with patient stratification will allow optimal evaluation in clinical studies.	[Liang, Dong; Khoonkari, Mohammad; Kruyt, Frank A. E.] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Hanzepl 1, NL-9713 GZ Groningen, Netherlands; [Avril, Tony; Chevet, Eric] Univ Rennes, INSERM U1242, Rennes, France; [Avril, Tony; Chevet, Eric] Ctr Lutte Canc Eugene Marquis, Rennes, France		Kruyt, FAE (corresponding author), Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Hanzepl 1, NL-9713 GZ Groningen, Netherlands.	f.a.e.kruyt@umcg.nl		Kruyt, Frank/0000-0002-2445-9380; Liang, Dong/0000-0002-7145-5569	China Scholarship CouncilChina Scholarship Council; University of Groningen; Zernike Institute for Advanced Materials at the University of Groningen; Bonus Incentive Scheme (Dutch Ministry for Education, Culture and Science (OCW)); La Ligue contre le cancer (comite 35); l'Institut des Neurosciences Cliniques de Rennes (AAP 2020); Fondation pour la Recherche Medicale (FRM equipe labellisee 2018); Institut National du Cancer (INCa; PLBIO)Institut National du Cancer (INCA) France; Agence Nationale de la Recherche (ANR; ERAAT)French National Research Agency (ANR); La Ligue contre le cancer (comite 56); La Ligue contre le cancer (comite 85)	DL was supported by the China Scholarship Council and the University of Groningen. MK was financially supported by the Zernike Institute for Advanced Materials at the University of Groningen, including funding from the Bonus Incentive Scheme (of the Dutch Ministry for Education, Culture and Science (OCW)). T. Avril was supported by La Ligue contre le cancer (comites 35, 56 and 85) and by l'Institut des Neurosciences Cliniques de Rennes (AAP 2020). EC was funded by Grants from Fondation pour la Recherche Medicale (FRM equipe labellisee 2018), Institut National du Cancer (INCa; PLBIO), Agence Nationale de la Recherche (ANR; ERAAT).	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Pharmacol.	OCT	2021	192								114737	10.1016/j.bcp.2021.114737		AUG 2021	7	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	US9US	WOS:000697771600011	34411568	Green Published, hybrid			2022-04-25	
J	Zhang, JT; Yi, M; Zha, LY; Chen, SQ; Li, ZJ; Li, C; Gong, MX; Deng, H; Chu, XW; Chen, JH; Zhang, ZQ; Mao, LM; Sun, SX				Zhang, Jintao; Yi, Man; Zha, Longying; Chen, Siqiang; Li, Zhijia; Li, Cheng; Gong, Mingxing; Deng, Hong; Chu, Xinwei; Chen, Jiehua; Zhang, Zheqing; Mao, Limei; Sun, Suxia			Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells: Implications for Apoptosis	PLOS ONE			English	Article							CHAIN FATTY-ACIDS; CYCLE ARREST; CANCER; DEATH; PATHWAYS; PROLIFERATION; INFLAMMATION; INHIBITOR; MECHANISM; TARGET	Purpose Butyrate, a short-chain fatty acid derived from dietary fiber, inhibits proliferation and induces cell death in colorectal cancer cells. However, clinical trials have shown mixed results regarding the anti-tumor activities of butyrate. We have previously shown that sodium butyrate increases endoplasmic reticulum stress by altering intracellular calcium levels, a well-known autophagy trigger. Here, we investigated whether sodium butyrate-induced endoplasmic reticulum stress mediated autophagy, and whether there was crosstalk between autophagy and the sodium butyrate-induced apoptotic response in human colorectal cancer cells. Methods Human colorectal cancer cell lines (HCT-116 and HT-29) were treated with sodium butyrate at concentrations ranging from 0.5-5mM. Cell proliferation was assessed using MTT tetrazolium salt formation. Autophagy induction was confirmed through a combination of Western blotting for associated proteins, acridine orange staining for acidic vesicles, detection of autolysosomes (MDC staining), and electron microscopy. Apoptosis was quantified by flow cytometry using standard annexinV/propidium iodide staining and by assessing PARP-1 cleavage by Western blot. Results Sodium butyrate suppressed colorectal cancer cell proliferation, induced autophagy, and resulted in apoptotic cell death. The induction of autophagy was supported by the accumulation of acidic vesicular organelles and autolysosomes, and the expression of autophagya-ssociated proteins, including microtubule-associated protein II light chain 3 (LC3-II), beclin-1, and autophagocytosis-associated protein (Atg)3. The autophagy inhibitors 3-methyladenine (3-MA) and chloroquine inhibited sodium butyrate induced autophagy. Furthermore, sodium butyrate treatment markedly enhanced the expression of endoplasmic reticulum stress-associated proteins, including BIP, CHOP, PDI, and IRE-1a. When endoplasmic reticulum stress was inhibited by pharmacological (cycloheximide and mithramycin) and genetic (siRNA targeting BIP and CHOP) methods, the induction of BIP, PDI, IRE1a, and LC3-II was blocked, but PARP cleavage was markedly enhanced. Discussion Taken together, these results suggested that sodium butyrate-induced autophagy was mediated by endoplasmic reticulum stress, and that preventing autophagy by blocking the endoplasmic reticulum stress response enhanced sodium butyrate-induced apoptosis. These results provide novel insights into the anti-tumor mechanisms of butyric acid.	[Zhang, Jintao; Yi, Man; Zha, Longying; Li, Zhijia; Li, Cheng; Gong, Mingxing; Deng, Hong; Chu, Xinwei; Chen, Jiehua; Zhang, Zheqing; Mao, Limei; Sun, Suxia] Southern Med Univ, Guangdong Prov Key Lab Trop Dis Res, Dept Nutr & Food Hyg, Sch Publ Hlth, 1023 South Sha Tai Rd, Guangzhou 510515, Guangdong, Peoples R China; [Chen, Siqiang] Guangdong Entry Exit Inspect & Quarantine Bur, Dept Certificat Supervis, Guojian Bldg,66,Huacheng Ave, Guangzhou 510623, Guangdong, Peoples R China		Sun, SX (corresponding author), Southern Med Univ, Guangdong Prov Key Lab Trop Dis Res, Dept Nutr & Food Hyg, Sch Publ Hlth, 1023 South Sha Tai Rd, Guangzhou 510515, Guangdong, Peoples R China.	suxiasun@hotmail.com		Sun, Suxia/0000-0002-1159-6191	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81202204]; Guangdong National Natural Science Foundation [S2012010009467]; Project for Excellent Young University Teacher	Financial support for this study was provided by National Natural Science Foundation of China (No. 81202204), Guangdong National Natural Science Foundation (No. S2012010009467), Project for Excellent Young University Teacher awarded to Southern Medical University.	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J	Xu, GQ; Yang, M; Wang, QL; Zhao, LF; Zhu, SJ; Zhu, LX; Xu, TR; Cao, RX; Li, C; Liu, QY; Xiong, W; Su, Y; Dong, J				Xu, Guoqiang; Yang, Mei; Wang, Qiaoli; Zhao, Liufang; Zhu, Sijin; Zhu, Lixiu; Xu, Tianrui; Cao, Ruixue; Li, Cheng; Liu, Qiuyan; Xiong, Wei; Su, Yan; Dong, Jian			A Novel Prognostic Prediction Model for Colorectal Cancer Based on Nine Autophagy-Related Long Noncoding RNAs	FRONTIERS IN ONCOLOGY			English	Article						colorectal cancer; autophagy; long noncoding RNAs; risk score; prognostic prediction model	CELL-PROLIFERATION; KNOCKDOWN; PCAT6; METASTASIS; PROGRESSION; STATISTICS; EXPRESSION; MIGRATION; INVASION; TUMOR	Introduction Colorectal cancer (CRC) is the most common gastrointestinal cancer and has a low overall survival rate. Tumor-node-metastasis staging alone is insufficient to predict patient prognosis. Autophagy and long noncoding RNAs play important roles in regulating the biological behavior of CRC. Therefore, establishing an autophagy-related lncRNA (ARlncRNA)-based bioinformatics model is important for predicting survival and facilitating clinical treatment. Methods CRC data were retrieved from The Cancer Genome Atlas. The database was randomly divided into train set and validation set; then, univariate and multivariate Cox regression analyses were performed to screen prognosis-related ARlncRNAs for prediction model construction. Interactive network and Sankey diagrams of ARlncRNAs and messenger RNAs were plotted. We analyzed the survival rate of high- and low-risk patients and plotted survival curves and determined whether the risk score was an independent predictor of CRC. Receiver operating characteristic curves were used to evaluate model sensitivity and specificity. Then, the expression level of lncRNA was detected by quantitative real-time polymerase chain reaction, and the location of lncRNA was observed by fluorescence in situ hybridization. Additionally, the protein expression was detected by Western blot. Results A prognostic prediction model of CRC was built based on nine ARlncRNAs (NKILA, LINC00174, AC008760.1, LINC02041, PCAT6, AC156455.1, LINC01503, LINC00957, and CD27-AS1). The 5-year overall survival rate was significantly lower in the high-risk group than in the low-risk group among train set, validation set, and all patients (all p < 0.001). The model had high sensitivity and accuracy in predicting the 1-year overall survival rate (area under the curve = 0.717). The prediction model risk score was an independent predictor of CRC. LINC00174 and NKILA were expressed in the nucleus and cytoplasm of normal colonic epithelial cell line NCM460 and colorectal cancer cell lines HT29. Additionally, LINC00174 and NKILA were overexpressed in HT29 compared with NCM460. After autophagy activation, LINCC00174 expression was significantly downregulated both in NCM460 and HT29, while NKILA expression was significantly increased. Conclusion The new ARlncRNA-based model predicts CRC patient prognosis and provides new research ideas regarding potential mechanisms regulating the biological behavior of CRC. ARlncRNAs may play important roles in personalized cancer treatment.	[Xu, Guoqiang; Wang, Qiaoli; Zhu, Sijin; Zhu, Lixiu; Xu, Tianrui; Cao, Ruixue; Li, Cheng; Xiong, Wei] Kunming Med Univ, Yunnan Canc Hosp, Dept Radiotherapy, Affiliated Hosp 3, Kunming, Yunnan, Peoples R China; [Yang, Mei] Kunming Med Univ, Yunnan Canc Hosp, Cadre Med Dept, Affiliated Hosp 3, Kunming, Yunnan, Peoples R China; [Zhao, Liufang] Kunming Med Univ, Yunnan Canc Hosp, Dept Head & Neck Surg 1, Affiliated Hosp 3, Kunming, Yunnan, Peoples R China; [Liu, Qiuyan] Panzhihua Univ, Panzhihua Integrated Tradit Chinese & Western Med, Dept Oncol, Affiliated Hosp, Panzhihua, Peoples R China; [Su, Yan] Kunming Med Univ, Yunnan Canc Hosp, Dept Grad Student Management, Affiliated Hosp 3, Kunming, Yunnan, Peoples R China; [Dong, Jian] Kunming Med Univ, Yunnan Canc Hosp, Dept Med Oncol, Affiliated Hosp 3, Kunming, Yunnan, Peoples R China		Xiong, W (corresponding author), Kunming Med Univ, Yunnan Canc Hosp, Dept Radiotherapy, Affiliated Hosp 3, Kunming, Yunnan, Peoples R China.; Su, Y (corresponding author), Kunming Med Univ, Yunnan Canc Hosp, Dept Grad Student Management, Affiliated Hosp 3, Kunming, Yunnan, Peoples R China.; Dong, J (corresponding author), Kunming Med Univ, Yunnan Canc Hosp, Dept Med Oncol, Affiliated Hosp 3, Kunming, Yunnan, Peoples R China.	panda_wei_wei@163.com; 1023445466@qq.com; ynszlyydj@163.com	Guoqiang, Xu/ABC-7298-2021; Zhao, Liufang/AFP-5716-2022	Guoqiang, Xu/0000-0003-3708-4167; Zhao, Liufang/0000-0003-3283-052X	Kunming Medical University	Funding This study was supported by Ten Thousand Plan Youth Talent Project in Yunnan Province and Innovation Fund project of Graduate Student in Kunming Medical University (2021S242).	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Oncol.	OCT 8	2021	11								613949	10.3389/fonc.2021.613949			15	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	WM2WM	WOS:000710950900001	34692467	Green Published, gold			2022-04-25	
J	Hu, WH; Yang, WC; Liu, PF; Liu, TT; Morgan, P; Tsai, WL; Pan, HW; Lee, CH; Shu, CW				Hu, Wan-Hsiang; Yang, Wen-Chi; Liu, Pei-Feng; Liu, Ting-Ting; Morgan, Paul; Tsai, Wei-Lun; Pan, Hung-Wei; Lee, Cheng-Hsin; Shu, Chih-Wen			Clinicopathological Association of Autophagy Related 5 Protein with Prognosis of Colorectal Cancer	DIAGNOSTICS			English	Article						autophagy; ATG5; prognosis; colorectal cancer	EXPRESSION	Gene mutation and pathogenesis bacteria are highly associated with colorectal cancer (CRC) development and progression. Autophagy is a self-clearance pathway to degrade abnormal proteins and infected bacteria in cells. Autophagy plays a dual role in cancer development. Among the autophagy-related (ATG) proteins, ATG5 is the key component required for the core machinery of autophagy. However, the role of ATG5 in CRC malignancy remains unclear. Herein, we found that a high ATG5 protein level was correlated with poor overall survival (OS) and disease-free survival (DFS) of 118 patients with CRC. After stratification with demographic and clinicopathologic factors, a high ATG5 protein level was significantly correlated with unfavorable overall survival in female and elder (>60 year) CRC patients and tumor tissues with poor differentiation, late T stages (III + IV), whereas the ATG5 protein level was positively associated with the overall survival in CRC patients without lymph node invasion and radiation therapy. In contrast, a high ATG5 protein level was significantly associated with worse DFS in CRC patients with early stage of AJCC and no radiation therapy. In addition, colorectal cancer cells stably harboring small interfering RNA (siRNA) against ATG5 diminished the tumorsphere formation and sensitized cancer cells to chemotherapeutic agents. Taken together, our results suggest that ATG5 might be a prognostic biomarker for CRC and a potential therapeutic target for CRC patients.	[Hu, Wan-Hsiang] Kaohsiung Chang Gung Mem Hosp, Dept Colorectal Surg, Kaohsiung 83341, Taiwan; [Hu, Wan-Hsiang; Liu, Ting-Ting] Chang Gung Univ, Coll Med, Kaohsiung 83341, Taiwan; [Hu, Wan-Hsiang] Chang Gung Univ, Grad Inst Clin Med Sci, Coll Med, Kaohsiung 83341, Taiwan; [Yang, Wen-Chi] E DA Hosp, Div Hematol & Med Oncol, Dept Internal Med, Kaohsiung 82445, Taiwan; [Yang, Wen-Chi; Morgan, Paul; Pan, Hung-Wei] I Shou Univ, Sch Med Int Students, Kaohsiung 82445, Taiwan; [Liu, Pei-Feng; Lee, Cheng-Hsin; Shu, Chih-Wen] Kaohsiung Med Univ, Dept Biomed Sci & Environm Biol, Kaohsiung 80708, Taiwan; [Liu, Pei-Feng] Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung 80708, Taiwan; [Liu, Ting-Ting] I Shou Univ, Dept Med Lab Sci, Kaohsiung 82445, Taiwan; [Liu, Ting-Ting] Kaohsiung Chang Gung Mem Hosp, Dept Pathol, Kaohsiung 83341, Taiwan; [Tsai, Wei-Lun] Kaohsiung Vet Gen Hosp, Dept Internal Med, Kaohsiung 81362, Taiwan; [Tsai, Wei-Lun] Natl Yang Ming Univ, Sch Med, Taipei 11221, Taiwan; [Shu, Chih-Wen] Natl Sun Yat Sen Univ, Inst Biopharmaceut Sci, Kaohsiung 80424, Taiwan		Shu, CW (corresponding author), Kaohsiung Med Univ, Dept Biomed Sci & Environm Biol, Kaohsiung 80708, Taiwan.; Shu, CW (corresponding author), Natl Sun Yat Sen Univ, Inst Biopharmaceut Sci, Kaohsiung 80424, Taiwan.	gary.hu0805@gmail.com; wenchi890079@gmail.com; pfliu908203@gmail.com; liutt107@cgmh.org.tw; buddymorgan@gmail.com; wltsai@vghks.gov.tw; d89444001@gmail.com; angioadsc@gmail.com; cwshu@g-mail.nsysu.edu.tw		Morgan, Paul/0000-0002-3231-0738; Yang, Wen-Chi/0000-0001-7062-5194; Shu, Chih-Wen/0000-0002-7774-0002; Liu, Pei-Feng/0000-0002-7849-8940	Ministry of Science and Technology MOSTMinistry of Science and Technology, China [108-2320-B-110008-MY3, 108-2320-B-075B-003]; Kaohsiung Chang Gung Memorial HospitalChang Gung Memorial Hospital [CMRPG8G1001]; E-Da hospital [EDAHP110041]	The work was supported by the Ministry of Science and Technology MOST (108-2320-B-110008-MY3 and 108-2320-B-075B-003), Kaohsiung Chang Gung Memorial Hospital (CMRPG8G1001) and E-Da hospital (EDAHP110041).	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J	Dashti, F; Mirazimi, SMA; Rabiei, N; Fathazam, R; Rabiei, N; Piroozmand, H; Vosough, M; Rahimian, N; Hamblin, MR; Mirzaei, H				Dashti, Fatemeh; Mirazimi, Seyed Mohammad Ali; Rabiei, Nikta; Fathazam, Reza; Rabiei, Negin; Piroozmand, Haleh; Vosough, Massoud; Rahimian, Neda; Hamblin, Michael R.; Mirzaei, Hamed			The role of non-coding RNAs in chemotherapy for gastrointestinal cancers	MOLECULAR THERAPY-NUCLEIC ACIDS			English	Review							HEPATOCELLULAR-CARCINOMA CELLS; HUMAN GASTRIC-CANCER; INCREASES DRUG-RESISTANCE; EPITHELIAL-MESENCHYMAL TRANSITION; DIFFERENTIAL MICRORNA EXPRESSION; REGULATES CISPLATIN-RESISTANCE; MODULATES MULTIDRUG-RESISTANCE; SENSITIZES COLORECTAL-CANCER; SUPPRESSES TUMOR-GROWTH; PANCREATIC-CANCER	Gastrointestinal (GI) cancers, including colorectal, gastric, hepatic, esophageal, and pancreatic tumors, are responsible for large numbers of deaths around the world. Chemotherapy is the most common approach used to treat advanced GI cancer. However, chemoresistance has emerged as a critical challenge that prevents successful tumor elimination, leading to metastasis and recurrence. Chemoresistance mechanisms are complex, and many factors and pathways are involved. Among these factors, non-coding RNAs (ncRNAs) are critical regulators of GI tumor development and subsequently can induce resistance to chemotherapy. This occurs because ncRNAs can target multiple signaling pathways, affect downstream genes, and modulate proliferation, apoptosis, tumor cell migration, and autophagy. ncRNAs can also induce cancer stem cell features and affect the epithelial-mesenchymal transition. Thus, ncRNAs could possibly act as new targets in chemotherapy combinations to treat GI cancer and to predict treatment response.	[Dashti, Fatemeh; Mirazimi, Seyed Mohammad Ali] Kashan Univ Med Sci, Sch Med, Kashan, Iran; [Dashti, Fatemeh; Mirazimi, Seyed Mohammad Ali] Kashan Univ Med Sci, Student Res Comm, Kashan, Iran; [Rabiei, Nikta; Fathazam, Reza; Rabiei, Negin] Shiraz Univ Med Sci, Sch Med, Shiraz, Iran; [Piroozmand, Haleh] Islamic Azad Univ, Fac Vet Sci, Sci & Res Branch, Tehran, Iran; [Vosough, Massoud] ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Regenerat Med, Tehran, Iran; [Rahimian, Neda] Iran Univ Med Sci IUMS, Endocrine Res Ctr, Inst Endocrinol & Metab, Tehran, Iran; [Hamblin, Michael R.] Univ Johannesburg, Fac Hlth Sci, Laser Res Ctr, ZA-2028 Doornfontein, South Africa; [Hamblin, Michael R.] Iran Univ Med Sci, Radiat Biol Res Ctr, Tehran, Iran; [Mirzaei, Hamed] Kashan Univ Med Sci, Res Ctr Biochem & Nutr Metab Dis, Inst Basic Sci, Kashan, Iran		Rahimian, N (corresponding author), Iran Univ Med Sci IUMS, Endocrine Res Ctr, Inst Endocrinol & Metab, Tehran, Iran.; Hamblin, MR (corresponding author), Univ Johannesburg, Fac Hlth Sci, Laser Res Ctr, ZA-2028 Doornfontein, South Africa.; 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Ther.-Nucl. Acids	DEC 3	2021	26						892	926		10.1016/j.omtn.2021.10.004		OCT 2021	35	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	XO4TH	WOS:000730179100013	34760336	Green Published, gold			2022-04-25	
J	Schiavano, GF; De Santi, M; Brandi, G; Fanelli, M; Bucchini, A; Giamperi, L; Giomaro, G				Schiavano, Giuditta Fiorella; De Santi, Mauro; Brandi, Giorgio; Fanelli, Mirco; Bucchini, Anahi; Giamperi, Laura; Giomaro, Giovanna			Inhibition of Breast Cancer Cell Proliferation and In Vitro Tumorigenesis by a New Red Apple Cultivar	PLOS ONE			English	Article							ANTIPROLIFERATIVE ACTIVITY; ANTIOXIDANT ACTIVITY; MAMMARY-TUMORS; FLAVONOIDS; COLON; VEGETABLES; APOPTOSIS; FRUIT; JUICE; CHEMOPREVENTION	Purpose The aim of this study was to evaluate the antiproliferative activity in breast cancer cells and the inhibition of tumorigenesis in pre-neoplastic cells of a new apple cultivar with reddish pulp, called the Pelingo apple. Methods The antiproliferative activity was evaluated in MCF-7 and MDA-MB-231 human breast cancer cells. The inhibition of tumorigenesis was performed in JB6 promotion-sensitive (P+) cells. Results Results showed that Pelingo apple juice is characterized by a very high polyphenol content and strongly inhibited breast cancer cell proliferation. Its antiproliferative activity was found to be higher than the other five apple juices tested. Pelingo juice induced cell accumulation in the G2/M phase of the cell cycle and autophagy through overexpression of p21, inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) activity and an increase in lipidated microtubule-associated protein-1 light chain-3 beta (LC3B). Remarkably, Pelingo juice inhibited the 12-o-tetra-decanoyl-phorbol-13-acetate (TPA)-induced tumorigenesis of JB6 P+ cells, suppressing colony formation in semi-solid medium and TPA-induced ERK1/2 phosphorylation. Conclusions Our data indicate that the Pelingo apple is rich in food components that can markedly inhibit in vitro tumorigenesis and growth of human breast cancer cells and could provide natural bioactive non-nutrient compounds, with potential chemopreventive activity.	[Schiavano, Giuditta Fiorella; De Santi, Mauro; Brandi, Giorgio; Fanelli, Mirco] Univ Urbino Carlo Bo, Dept Biomol Sci, Urbino, PU, Italy; [Bucchini, Anahi; Giamperi, Laura; Giomaro, Giovanna] Univ Urbino Carlo Bo, Dept Earth Life & Environm Sci, Urbino, PU, Italy		Schiavano, GF (corresponding author), Univ Urbino Carlo Bo, Dept Biomol Sci, Urbino, PU, Italy.	giuditta.schiavano@uniurb.it	Fanelli, Mirco/F-2665-2011; De Santi, Mauro/F-5401-2013	Fanelli, Mirco/0000-0002-9649-8661; De Santi, Mauro/0000-0003-2983-8344; Schiavano, Giuditta Fiorella/0000-0002-1427-3486; Bucchini, Anahi Elena Ada/0000-0003-3100-9262; Brandi, Giorgio/0000-0003-1380-6137			Amatori S, 2010, BRIT J CANCER, V103, P239, DOI 10.1038/sj.bjc.6605745; Barth SW, 2005, CARCINOGENESIS, V26, P1414, DOI 10.1093/carcin/bgi082; BLOCK G, 1992, NUTR CANCER, V18, P1, DOI 10.1080/01635589209514201; Boeing H, 2012, EUR J NUTR, V51, P637, DOI 10.1007/s00394-012-0380-y; Boyer J, 2004, NUTR J, V3, DOI 10.1186/1475-2891-3-5; Brandi G, 2005, J NUTR, V135, P1503, DOI 10.1093/jn/135.6.1503; Brandi G, 2003, CANCER RES, V63, P4028; Chen MS, 2004, IN VIVO, V18, P73; Dalla Ragione L., 2006, ARCHEOLOGIA ARBOREA, P102; Danaei G, 2005, LANCET, V366, P1784, DOI 10.1016/S0140-6736(05)67725-2; de Pascual-Teresa Sonia, 2008, Phytochemistry Reviews, V7, P281, DOI 10.1007/s11101-007-9074-0; De Santi M, 2011, BREAST CANCER RES, V13, DOI 10.1186/bcr2855; Eberhardt MV, 2000, NATURE, V405, P903, DOI 10.1038/35016148; Elisia I, 2007, FOOD CHEM, V101, P1052, DOI 10.1016/j.foodchem.2006.02.060; Fraternale D, 2011, REC NAT PROD, V5, P202; Gallus S, 2005, ANN ONCOL, V16, P1841, DOI 10.1093/annonc/mdi361; Galluzzi L, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0043249; Gescher AJ, 2008, PLANTA MED, V74, P1523, DOI [10.1055/s-0028-1088305, 10.1055/s-0028-1088300]; Giomaro G, 2014, CHEM CENT J, V8, DOI 10.1186/1752-153X-8-45; HAGERMAN AE, 1994, METHOD ENZYMOL, V234, P429; He X, 2008, J AGR FOOD CHEM, V56, P9905, DOI 10.1021/jf8015255; He XJ, 2007, J AGR FOOD CHEM, V55, P4366, DOI 10.1021/jf063563o; Hyson DA, 2011, ADV NUTR, V2, P408, DOI 10.3945/an.111.000513; Kang NJ, 2011, PHARMACOL THERAPEUT, V130, P310, DOI 10.1016/j.pharmthera.2011.02.004; Key TJ, 2011, BRIT J CANCER, V104, P6, DOI 10.1038/sj.bjc.6606032; Knekt P, 1997, AM J EPIDEMIOL, V146, P223, DOI 10.1093/oxfordjournals.aje.a009257; Vieira FGK, 2009, ARCH LATINOAM NUTR, V59, P101; Kuntz S, 1999, EUR J NUTR, V38, P133, DOI 10.1007/s003940050054; Lagiou P, 2004, CANCER CAUSE CONTROL, V15, P67, DOI 10.1023/B:CACO.0000016619.18041.b0; Le Marchand L, 2000, JNCI-J NATL CANCER I, V92, P154, DOI 10.1093/jnci/92.2.154; Li JX, 2012, CARCINOGENESIS, V33, P459, DOI 10.1093/carcin/bgr281; Liu JR, 2009, J AGR FOOD CHEM, V57, P297, DOI 10.1021/jf801826w; Liu R. 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J	Chou, TF; Li, KL; Frankowski, KJ; Schoenen, FJ; Deshaies, RJ				Chou, Tsui-Fen; Li, Kelin; Frankowski, Kevin J.; Schoenen, Frank J.; Deshaies, Raymond J.			Structure-Activity Relationship Study Reveals ML240 and ML241 as Potent and Selective Inhibitors of p97 ATPase	CHEMMEDCHEM			English	Article						AAA ATPase; autophagy; cancer; structure-activity relationships; ubiquitin proteasome	AAA-ATPASE; PROTEIN VCP; UBIQUITIN; CDC48/P97; COMPLEX; MEDIATE; P97/VCP; DOMAIN; LINKS; ER	To discover more potent p97 inhibitors, we carried out a structureactivity relationship study of the quinazoline scaffold previously identified from our HTS campaigns. Two improved inhibitors, ML240 and ML241, inhibit p97 ATPase with IC50 values of 100 nM. Both compounds inhibited degradation of a p97-dependent but not a p97-independent proteasome substrate in a dual-reporter cell line. They also impaired the endoplasmic-reticulum-associated degradation (ERAD) pathway. Unexpectedly, ML240 potently stimulated accumulation of LC3-II within minutes, inhibited cancer cell growth, and rapidly mobilized the executioner caspases 3 and 7, whereas ML241 did not. The behavior of ML240 suggests that disruption of the protein homeostasis function of p97 leads to more rapid activation of apoptosis than is observed with a proteasome inhibitor. Further characterization revealed that ML240 has broad antiproliferative activity toward the NCI-60 panel of cancer cell lines, but slightly lower activity toward normal cells. ML240 also synergizes with the proteasome inhibitor MG132 to kill multiple colon cancer cell lines. Meanwhile, both probes have low off-target activity toward a panel of protein kinases and central nervous system targets. Our results nominate ML240 as a promising starting point for the development of a novel agent for the chemotherapy of cancer, and provide a rationale for developing pathway-specific p97 inhibitors.	[Chou, Tsui-Fen; Deshaies, Raymond J.] CALTECH, Div Biol, Pasadena, CA 91125 USA; [Chou, Tsui-Fen; Deshaies, Raymond J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA; [Li, Kelin; Frankowski, Kevin J.; Schoenen, Frank J.] Univ Kansas, Specialized Chem Ctr, Struct Biol Ctr, Lawrence, KS 66047 USA; [Chou, Tsui-Fen] Harbor UCLA Med Ctr, Dept Pediat, Div Med Genet, Torrance, CA 90502 USA; [Chou, Tsui-Fen] Los Angeles Biomed Res Inst, Torrance, CA 90502 USA		Chou, TF (corresponding author), CALTECH, Div Biol, 1200 E Calif Blvd, Pasadena, CA 91125 USA.	tsuifenchou@ucla.edu; deshaies@caltech.edu	Deshaies, Raymond/B-8354-2014	Deshaies, Raymond/0000-0002-3671-9354; Schoenen, Frank/0000-0003-2711-1117	National Institute of Mental Health's Psychoactive Drug Screening ProgramUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [HHSN-271-2008-00025-C]; NIH Molecular Libraries Probe Production Centers Network [5U54HG005031]; Howard Hughes Medical InstituteHoward Hughes Medical Institute; NATIONAL HUMAN GENOME RESEARCH INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [U54HG005031] Funding Source: NIH RePORTER	We thank B. E. Nordin and M. P. Patricelli (ActivX Biosciences La Jolla, CA, USA) for analyzing the ACJI-47 positive control free of charge in the kinase profiling experiments. K<INF>i</INF> determinations and receptor binding profiles were generously provided by the National Institute of Mental Health's Psychoactive Drug Screening Program, Contract no. HHSN-271-2008-00025-C (NIMH PDSP). The NIMH PDSP is Directed by Bryan L. Roth, MD PhD (University of North Carolina, Chapel Hill, NC, USA) and Project Officer Jamie Driscol (NIMH, Bethesda MD, USA). The NCI 60-cell-line screen was performed by the Developmental Therapeutics Program at the NCI. We thank Jeffrey Aube (University of Kansas, Lawrence, KS, USA) for helpful discussions, P. Porubsky (University of Kansas) for compound management, Ben Neuenswander (University of Kansas) for compound purification and high-resolution mass determination, Justin Douglas and Sarah Neuenswander (University of Kansas) for NMR assistance, R. Weinberg (Massachusetts Institute of Technology, Cambridge, MA, USA) via H. Chang (Stanford University, CA, USA) for providing PHMLEB and PHMLER cells, K. S. Osthoff (Eberhard Karls University, Tubingen, Germany) via G. M. Cohen (University of Leicester, UK) for caspase 9-/- cells, G. Salvesen (Sanford-Burnham Medical Research Institute) for caspase 8-/- cells, and H. Park, R. Oania, and D. Shimoda for technical assistance. This work was supported by a grant from the NIH Molecular Libraries Probe Production Centers Network to Jeffrey Aube (PI) (5U54HG005031). R.J.D. and T.-F.C. were supported by the Howard Hughes Medical Institute, of which R.J.D. is an Investigator.	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J	Lokireddy, S; Wijesoma, IW; Bonala, S; Wei, M; Sze, SK; McFarlane, C; Kambadur, R; Sharma, M				Lokireddy, Sudarsanareddy; Wijesoma, Isuru Wijerupage; Bonala, Sabeera; Wei, Meng; Sze, Siu Kwan; McFarlane, Craig; Kambadur, Ravi; Sharma, Mridula			RETRACTED: Myostatin is a novel tumoral factor that induces cancer cachexia (Retracted article. See vol. 473, pg. 1111, 2016)	BIOCHEMICAL JOURNAL			English	Article; Retracted Publication						activin receptor type II B; autophagy-lysosome system; myostatin; nuclear factor kappa B (NF-kappa B); reactive oxygen species (ROS); skeletal muscle wasting; tumoral factor; ubiquitin-proteasome system	SKELETAL-MUSCLE HYPERTROPHY; MITOCHONDRIAL E3; PATHWAYS; ATROPHY; DIFFERENTIATION; ACTIVATION; MECHANISMS; PROTEINS; DYNAMICS; COMPLEX	Humoral and tumoral factors collectively promote cancer-induced skeletal muscle wasting by increasing protein degradation. Although several humoral proteins, namely TNF alpha (tumour necrosis factor alpha) and IL (interleukin)-6, have been shown to induce skeletal muscle wasting, there is a lack of information regarding the tumoral factors that contribute to the atrophy of muscle during cancer cachexia. Therefore, in the present study, we have characterized the secretome of C26 colon cancer cells to identify the tumoral factors involved in cancer-induced skeletal muscle wasting. In the present study, we show that myostatin, a procachectic TGF beta (transforming growth factor beta) superfamily member, is abundantly secreted by C26 cells. Consistent with myostatin signalling during cachexia, treating differentiated C2C12 myotubes with C26 CM (conditioned medium) resulted in myotubular atrophy due to the up-regulation of muscle-specific E3 ligases, atrogin-1 and MuRF1 (muscle RING-finger protein 1), and enhanced activity of the ubiquitin proteasome pathway. Furthermore, the C26 CM also activated ActRIIB (activin receptor type II B)/Smad and NF-kappa B (nuclear factor kappa B) signalling, and reduced the activity of the IGF-I (insulin-like growth factor 1)/P13K (phosphoinositide 3-kinase)/Akt pathway, three salient molecular features of myostatin action in skeletal muscles. Antagonists to myostatin prevented C26 CM-induced wasting in muscle cell cultures, further confirming that tumoral myostatin may be a key contributor in the pathogenesis of cancer cachexia. Finally, we show that treatment with C26 CM induced the autophagy-lysosome pathway and reduced the number of mitochondria in myotubes. These two previously unreported observations were recapitulated in skeletal muscles collected from C26 tumour-bearing mice.	[Sharma, Mridula] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117595, Singapore; [Lokireddy, Sudarsanareddy; Wijesoma, Isuru Wijerupage; Bonala, Sabeera; Wei, Meng; Sze, Siu Kwan; Kambadur, Ravi] Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore; [McFarlane, Craig; Kambadur, Ravi] ASTAR, Singapore Inst Clin Sci, Singapore, Singapore		Sharma, M (corresponding author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117595, Singapore.	bchmridu@nus.edu.sg	Sze, Siu Kwan/AAO-3342-2020	Sze, Siu Kwan/0000-0002-5652-1687	NICHD (National Institute of Child Health and Human Development)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); MOE (Ministry of Education), SingaporeMinistry of Education, Singapore [T208B3211]; BMRC (Biomedical Research Council), SingaporeAgency for Science Technology & Research (ASTAR) [07/1/21/19/521]	We thank Esther Latres (Regeneron Pharmaceuticals, Tarrytown, NJ, U.S.A.) for providing the anti-atrogin-1 and anti-MuRF1 antibodies used in the present study. The MF20 and T14 monoclonal antibodies developed by Donald A. Fischman and Frank E. Stockdale respectively were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD (National Institute of Child Health and Human Development) and maintained by Department of Biology, The University of Iowa, Iowa City, IA, U.S.A. Finally, we thank Addgene (Cambridge, MA, U.S.A.) for providing the reporter vectors [FoxO3 (Dr Michael Greenberg, #1789), PGC-1 alpha (Dr Bruce Spiegelman, #8887) and 4X SBE (Dr Bert Vogelstein, #16495)].; This work was supported by the MOE (Ministry of Education), Singapore [grant number T208B3211] and BMRC (Biomedical Research Council), Singapore [grant number 07/1/21/19/521].	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J.	AUG 15	2012	446		1				23	36		10.1042/BJ20112024			14	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	990JH	WOS:000307626300003	22621320	hybrid, Green Published			2022-04-25	
J	Lembo-Fazio, L; Nigro, G; Noel, G; Rossi, G; Chiara, F; Tsilingiri, K; Rescigno, M; Rasola, A; Bernardini, ML				Lembo-Fazio, L.; Nigro, G.; Noel, G.; Rossi, G.; Chiara, F.; Tsilingiri, K.; Rescigno, M.; Rasola, A.; Bernardini, M. L.			Gadd45 alpha activity is the principal effector of Shigella mitochondria-dependent epithelial cell death in vitro and ex vivo	CELL DEATH & DISEASE			English	Article						apoptosis; mitochondria; Shigella; infection; Gadd45 alpha	MONOCYTE-DERIVED MACROPHAGES; GROWTH-ARREST; CANCER-CELL; APOPTOSIS; FLEXNERI; NECROSIS; MULTIPLICATION; INFECTION; AUTOPHAGY; RESPONSES	Modulation of death is a pathogen strategy to establish residence and promote survival in host cells and tissues. Shigella spp. are human pathogens that invade colonic mucosa, where they provoke lesions caused by their ability to manipulate the host cell responses. Shigella spp. induce various types of cell death in different cell populations. However, they are equally able to protect host cells from death. Here, we have investigated on the molecular mechanisms and cell effectors governing the balance between survival and death in epithelial cells infected with Shigella. To explore these aspects, we have exploited both, the HeLa cell invasion assay and a novel ex vivo human colon organ culture model of infection that mimics natural conditions of shigellosis. Our results definitely show that Shigella induces a rapid intrinsic apoptosis of infected cells, via mitochondrial depolarization and the ensuing caspase-9 activation. Moreover, for the first time we identify the eukaryotic stress-response factor growth arrest and DNA damage 45 alpha as a key player in the induction of the apoptotic process elicited by Shigella in epithelial cells, revealing an unexplored role of this molecule in the course of infections sustained by invasive pathogens. Cell Death and Disease ( 2011) 2, e122; doi: 10.1038/cddis.2011.4; published online 24 February 2011	[Bernardini, M. L.] Univ Roma La Sapienza, Inst Pasteur, Fdn Cenci Bolognetti, Dipartimento Biol & Biotecnol Charles Darwin, I-00185 Rome, Italy; [Rossi, G.] Univ Camerino, Dipartimento Sci Vet, Matelica, Macerata, Italy; [Chiara, F.; Rasola, A.] Univ Padua, Dipartimento Sci Biomed, Padua, Italy; [Chiara, F.] Univ Padua, Dipartimento Med Ambientale & Sanita Pubbl, Padua, Italy; [Tsilingiri, K.; Rescigno, M.] Inst Oncol, Dept Expt Oncol European, Milan, Italy		Bernardini, ML (corresponding author), Univ Roma La Sapienza, Inst Pasteur, Fdn Cenci Bolognetti, Dipartimento Biol & Biotecnol Charles Darwin, Via Dei Sardi 70, I-00185 Rome, Italy.	marialina.bernardini@uniroma1.it	Rescigno, Maria/J-9704-2012	Rescigno, Maria/0000-0002-6464-509X; chiara, federica/0000-0003-2396-3080; BERNARDINI, Maria/0000-0002-4305-7694; Lembo Fazio, Luigi/0000-0001-5684-9191; Rasola, Andrea/0000-0003-4522-3008	Italian 'Ministero dell'Istruzione, Universita e Ricerca'Ministry of Education, Universities and Research (MIUR); Luigi Lembo-Fazio; Marie-Curie fellowshipEuropean Commission; cross-talk network	This work was partially supported by grants from the Italian 'Ministero dell'Istruzione, Universita e Ricerca' (PRIN 2009). Luigi Lembo-Fazio, Giulia Nigro and Gaelle Noel were fellows of the 'Istituto Pasteur-Fondazione Cenci Bolognetti'. Katerina Tsilingiri is a recipient of a Marie-Curie fellowship within the cross-talk network.	Carneiro LAM, 2009, CELL HOST MICROBE, V5, P123, DOI 10.1016/j.chom.2008.12.011; Cersini A, 1998, INFECT IMMUN, V66, P549, DOI 10.1128/IAI.66.2.549-557.1998; Chipuk JE, 2010, MOL CELL, V37, P299, DOI 10.1016/j.molcel.2010.01.025; Deretic V, 2009, CELL HOST MICROBE, V5, P527, DOI 10.1016/j.chom.2009.05.016; Downward J, 2004, SEMIN CELL DEV BIOL, V15, P177, DOI 10.1016/j.semcdb.2004.01.002; Dupont N, 2009, CELL HOST MICROBE, V6, P137, DOI 10.1016/j.chom.2009.07.005; Faherty CS, 2009, INFECT IMMUN, V77, P5281, DOI 10.1128/IAI.00800-09; Gao M, 2009, CURR PROTEIN PEPT SC, V10, P388, DOI 10.2174/138920309788922216; Girardin SE, 2003, SCIENCE, V300, P1584, DOI 10.1126/science.1084677; Gramaglia D, 2004, CELL DEATH DIFFER, V11, P342, DOI 10.1038/sj.cdd.4401326; Hasegawa Y, 2007, INFECT IMMUN, V75, P2540, DOI 10.1128/IAI.01957-06; Hilbi H, 1997, INFECT IMMUN, V65, P5165, DOI 10.1128/IAI.65.12.5165-5170.1997; Hoffman B, 2009, J CELL PHYSIOL, V218, P26, DOI 10.1002/jcp.21582; Koterski JF, 2005, INFECT IMMUN, V73, P504, DOI 10.1128/IAI.73.1.504-513.2005; Labbe K, 2008, CELL DEATH DIFFER, V15, P1339, DOI 10.1038/cdd.2008.91; Li YF, 2009, J GENE MED, V11, P3, DOI 10.1002/jgm.1270; Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262; Martino MC, 2005, J INFECT DIS, V192, P136, DOI 10.1086/430740; Martinoli C, 2007, IMMUNITY, V27, P975, DOI 10.1016/j.immuni.2007.10.011; MATHAN VI, 1991, REV INFECT DIS, V13, pS311; Nicotera P, 2004, ONCOGENE, V23, P2757, DOI 10.1038/sj.onc.1207559; Nonaka T, 1999, FEMS MICROBIOL LETT, V174, P89, DOI 10.1111/j.1574-6968.1999.tb13553.x; O'Reilly MA, 2000, AM J PHYSIOL-LUNG C, V278, pL552, DOI 10.1152/ajplung.2000.278.3.L552; Orrenius S, 2003, NAT REV MOL CELL BIO, V4, P552, DOI 10.1038/nrm1150; Parsot C, 1994, Curr Top Microbiol Immunol, V192, P217; Pedron T, 2003, J BIOL CHEM, V278, P33878, DOI 10.1074/jbc.M303749200; Pendaries C, 2006, EMBO J, V25, P1024, DOI 10.1038/sj.emboj.7601001; Rasola A, 2001, CYTOMETRY, V45, P151, DOI 10.1002/1097-0320(20011001)45:2<151::AID-CYTO1157>3.0.CO;2-I; Rasola A, 2007, APOPTOSIS, V12, P815, DOI 10.1007/s10495-007-0723-y; Rasola A, 2010, FEBS LETT, V584, P1989, DOI 10.1016/j.febslet.2010.02.022; Resendes AR, 2004, VET IMMUNOL IMMUNOP, V99, P203, DOI 10.1016/j.vetimm.2004.02.001; Rudel T, 2010, NAT REV MICROBIOL, V8, P693, DOI 10.1038/nrmicro2421; SANSONETTI PJ, 1986, INFECT IMMUN, V51, P461, DOI 10.1128/IAI.51.2.461-469.1986; Siafakas AR, 2009, INT J BIOCHEM CELL B, V41, P986, DOI 10.1016/j.biocel.2008.06.018; Srinivasula SM, 2008, MOL CELL, V30, P123, DOI 10.1016/j.molcel.2008.03.008; Suzuki T, 2005, J BIOL CHEM, V280, P14042, DOI 10.1074/jbc.M414671200; Suzuki T, 2007, PLOS PATHOG, V3, P1082, DOI 10.1371/journal.ppat.0030111; Tattoli I, 2008, MICROBES INFECT, V10, P1114, DOI 10.1016/j.micinf.2008.06.004; Tong T, 2005, MOL CELL BIOL, V25, P4488, DOI 10.1128/MCB.25.11.4488-4500.2005; Zerbini LF, 2004, P NATL ACAD SCI USA, V101, P13618, DOI 10.1073/pnas.0402069101	40	19	19	0	3	NATURE PUBLISHING GROUP	LONDON	MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND	2041-4889			CELL DEATH DIS	Cell Death Dis.	FEB	2011	2								e122	10.1038/cddis.2011.4			12	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	726CH	WOS:000287695600005	21368893	Green Published, gold			2022-04-25	
J	Zhang, HY; Lei, YL; Yuan, P; Li, LJ; Luo, C; Gao, R; Tian, J; Feng, ZH; Nice, EC; Sun, J				Zhang, Haiyuan; Lei, Yunlong; Yuan, Ping; Li, Lingjun; Luo, Chao; Gao, Rui; Tian, Jun; Feng, Zuohua; Nice, Edouard C.; Sun, Jun			ROS-Mediated Autophagy Induced by Dysregulation of Lipid Metabolism Plays a Protective Role in Colorectal Cancer Cells Treated with Gambogic Acid	PLOS ONE			English	Article							MALIGNANT GLIOMA-CELLS; INDUCED APOPTOSIS; TUMOR PROGRESSION; OXIDATIVE STRESS; REDOX REGULATION; KAPPA-B; OXYGEN; DEATH; ACTIVATION; INDUCTION	Gambogic acid (GA), the main active component of gamboge resin, has potent antitumor activity both in vivo and in vitro. However, the underlying molecular mechanisms remain unclear. In this study, we found that GA could initiate autophagy in colorectal cancer cells, and inhibition of the autophagy process accelerated the effect of proliferative inhibition and apoptotic cell death induced by GA, implying a protective role of autophagy. Two-dimensional electrophoresis-based proteomics showed that GA treatment altered the expression of multiple proteins involved in redox signaling and lipid metabolism. Functional studies revealed that GA-induced dysregulation of lipid metabolism could activate 5-lipoxygenase (5-LOX), resulting in intracellular ROS accumulation, followed by inhibition of Akt-mTOR signaling and autophagy initiation. Finally, results using a xenograft model suggested ROS-induced autophagy protect against the antitumor effect of GA. Taken together, these data showed new biological activities of GA against colorectal cancer underlying the protective role of ROS-induced autophagy. This study will provide valuable insights for future studies regarding the anticancer mechanisms of GA.	[Zhang, Haiyuan; Yuan, Ping; Li, Lingjun; Luo, Chao; Gao, Rui; Tian, Jun; Feng, Zuohua; Sun, Jun] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Biochem & Mol Biol, Wuhan 430074, Peoples R China; [Lei, Yunlong] Chongqing Med Univ, Dept Biochem & Mol Biol, Chongqing, Peoples R China; [Lei, Yunlong] Chongqing Med Univ, Mol Med & Canc Res Ctr, Chongqing, Peoples R China; [Nice, Edouard C.] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia		Sun, J (corresponding author), Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Biochem & Mol Biol, Wuhan 430074, Peoples R China.	sun_jun99@163.com		Lei, Yunlong/0000-0002-7918-0221	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [30672480]; National High Technology Research and Development Program of China (863 Program)National High Technology Research and Development Program of China [2012AA020201]; National 973 Basic Research Program of ChinaNational Basic Research Program of China [2013CB911300]; Education Department of Hubei province science and technology research projects of outstanding young talent project [Q20091207]	This work was supported by grants from National Natural Science Foundation of China (Grant number: 30672480), National High Technology Research and Development Program of China (863 Program; No. 2012AA020201), the National 973 Basic Research Program of China (2013CB911300) and the Education Department of Hubei province science and technology research projects of outstanding young talent project(Q20091207). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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Zhao L, 2004, BIOL PHARM BULL, V27, P998, DOI 10.1248/bpb.27.998; Zhao Q, 2008, CANCER LETT, V262, P223, DOI 10.1016/j.canlet.2007.12.002; Zhou S, 2012, MASS SPECTROMETRY RE; [周政涛 ZHOU Zhengtao], 2007, [中国新药杂志, Chinese Journal New Drugs], V16, P79; Zou ZY, 2012, BMC COMPLEM ALTERN M, V12, DOI 10.1186/1472-6882-12-58	91	37	40	4	33	PUBLIC LIBRARY SCIENCE	SAN FRANCISCO	1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA	1932-6203			PLOS ONE	PLoS One	MAY 8	2014	9	5							e96418	10.1371/journal.pone.0096418			14	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	AK1XT	WOS:000338213300035	24810758	Green Submitted, Green Published, gold			2022-04-25	
J	Duan, P; Hu, CH; Quan, C; Yu, TT; Zhou, W; Yuan, M; Shi, YQ; Yang, KD				Duan, Peng; Hu, Chunhui; Quan, Chao; Yu, Tingting; Zhou, Wei; Yuan, Meng; Shi, Yuqin; Yang, Kedi			4-Nonylphenol induces apoptosis, autophagy and necrosis in Sertoli cells: Involvement of ROS-mediated AMPK/AKT-mTOR and JNK pathways	TOXICOLOGY			English	Article						4-Nonylphenol; Sertoli cells; Apoptosis; Autophagy; ROS; AMPK/Akt/JNK signalling	ACTIVATED PROTEIN-KINASE; BPA-INDUCED APOPTOSIS; COLON-CANCER CELLS; SIGNALING PATHWAY; CYCLE ARREST; AKT/MTOR PATHWAY; DOWN-REGULATION; STEM-CELLS; TM4 CELLS; IN-VITRO	The xenoestrogen 4-nonylphenol (NP) induces reproductive dysfunction of male rats, but the fundamental mechanism of this phenomenon is largely unexplored. Sertoli cells (SCs) are pivotal for spermatogenesis and male fertility. The involvement of autophagy in NP-induced apoptotic and necrotic death of SCs was investigated. In this study, 24-h exposure of SCs to 20-30 mu M NP decreased cell viability, caused G2/M arrest, triggered Delta Psi m loss, increased ROS production and induced caspase-dependent apoptsis, necrosis as well as autophagosome formation. NP-induced autophagy was confirmed by monodansylcadaverine-staining and LC3-I/LC3-II conversion. Furthermore, NP up-regulated the (Thr)172p- AMPK/AMPK and (Thr183/185)p-JNK/JNK ratios. This was followed by the down-regulation of Ser(473)p-Akt/Akt, (Thr1462)p-TSC2/TSC2, (ser2448)p-mTOR/mTOR, (Thr389)p-p70S6K/p70S6K and (Thr37/45)p-4EBP1/4EBP1. Intriguingly, NP-induced apoptosis, autophagy and necrosis could be inhibited through blocking ROS generation by N-acetylcysteine. Autophagy inhibitor 3-MA enhanced NP-induced apoptosis and necrosis. Moreover, The activation of AMPK/mTOR/p70s6k/4EBP1 and JNK signalling pathways induced by NP could be efficiently reversed by pretreatment of N-acetylcysteine or 3-MA. Collectively, our findings provide the first evidence that NP promotes apoptosis, autophagy and necrosis simultaneously in SCs and that this process may involve ROS-dependent JNK- and Akt/AMPK/mTOR pathways. Modulation of autophagy induced by NP may serve as a survival mechanism against apoptosis and necrosis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.	[Duan, Peng; Quan, Chao; Yu, Tingting; Zhou, Wei; Yuan, Meng; Yang, Kedi] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Occupat & Environm Hlth, MOE Minist Educ,Key Lab Environm & Hlth, Wuhan 430030, Peoples R China; [Hu, Chunhui] Hubei Univ Med, Dept Lab Med, Taihe Hosp, Shiyan 442000, Hubei, Peoples R China; [Shi, Yuqin] Wuhan Univ Sci & Technol, Coll Med, Sch Publ Hlth, Dept Epidemiol & Hlth Stat, Wuhan 430030, Peoples R China		Yang, KD (corresponding author), Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Occupat & Environm Hlth, 13 Hangkong Rd, Wuhan 430030, Hubei Province, Peoples R China.	yangkd@mails.tjmu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81372960, 81172623]	This work is supported by grants from The National Natural Science Foundation of China (grant number: 81372960, 81172623).	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J	Wang, YY; Qin, C; Yang, G; Zhao, BB; Wang, WB				Wang, Yuanyang; Qin, Cheng; Yang, Gang; Zhao, Bangbo; Wang, Weibin			The role of autophagy in pancreatic cancer progression	BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER			English	Review						Pancreatic cancer; Autophagy; Epithelial-mesenchymal transition; Glucose metabolism; Immunotherapy; Chemoresistance	EPITHELIAL-MESENCHYMAL TRANSITION; DUCTAL ADENOCARCINOMA; HEPATOCELLULAR-CARCINOMA; GEMCITABINE RESISTANCE; COLORECTAL-CANCER; STELLATE CELLS; GROWTH; INHIBITION; INVASION; SURVIVAL	Patients with pancreatic cancer have an abysmal survival rate. The poor prognosis of pancreatic cancer is due to the difficulty of making an early diagnosis, high rate of metastasis, and frequent chemoresistance. In recent years, as a self-regulatory procedure within cells, the effect and mechanism of autophagy have been explored. Dysregulated autophagy serves as a double-edged sword in cancer development in which autophagy inhibits cancer initiation but promotes cancer progression. After tumor formation, activation of autophagy can induce epithelialmesenchymal transition, regulate metabolism, specifically glutamine usage and the glycolytic process, and mediate drug resistance in pancreatic cancer. Multiple genes, RNA molecules, proteins, and certain drugs exert antitumor effects by inhibiting autophagy-mediated drug resistance. Several clinical trials have combined autophagy inhibitors with chemotherapeutic drugs in pancreatic cancer treatment, some of which have shown promising results. In conclusion, autophagy plays a vital role in pancreatic cancer progression and deserves further study.	[Wang, Yuanyang; Qin, Cheng; Yang, Gang; Zhao, Bangbo; Wang, Weibin] Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Gen Surg,State Key Lab Complex Severe & Rare, Beijing 100730, Peoples R China		Wang, WB (corresponding author), Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Gen Surg,State Key Lab Complex Severe & Rare, Beijing 100730, Peoples R China.	pumc_wangyuanyang@student.pumc.edu.cn; wwb_xh@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81773215]; Chinese Academy of Medical Sciences [2019XK320002]	WWB received support from the National Natural Science Foundation of China (No.81773215) and the Chinese Academy of Medical Sciences (No.2019XK320002).	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Biophys. Acta-Rev. Cancer	DEC	2021	1876	2							188592	10.1016/j.bbcan.2021.188592		JUL 2021	11	Biochemistry & Molecular Biology; Biophysics; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics; Oncology	US0WQ	WOS:000697158300007	34274449				2022-04-25	
J	Lin, ZY; Yun, QZ; Wu, L; Zhang, TW; Yao, TZ				Lin, Zhu Yue; Yun, Qu Zhen; Wu, Liu; Zhang, Tian Wen; Yao, Tang Ze			Pharmacological basis and new insights of deguelin concerning its anticancer effects	PHARMACOLOGICAL RESEARCH			English	Article						Deguelin; Anticancer; Apoptosis; PI3K/Akt signaling pathway; NF-kappa B signaling pathway; Wnt signaling pathway	TO-MESENCHYMAL TRANSITION; COLON-CANCER CELLS; LUNG-CANCER; BIOLOGICAL EVALUATION; HSP90 ACTIVITY; AKT INHIBITOR; TUMOR-GROWTH; APOPTOSIS; METASTASIS; MIGRATION	Deguelin is a rotenoid of the flavonoid family, which can be extracted from Lonchocarpus, Derris, or Tephrosia. It possesses the inhibition of cancer cell proliferation by inducing apoptosis through regulating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, the NF-kappa B signaling pathway, the Wnt signaling pathway, the adenosine 5 '-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway and epidermal growth factor receptor (EGFR) signaling, activating the p38 mitogen-activated protein kinase (MAPK) pathway, repression of Bmi1, targeting cyclooxygenase-2 (COX-2), targeting galectin-1, promotion of glycogen synthase kinase-3 beta (GSK3 beta)/FBW7-mediated Mcl-1 destabilization and targeting mitochondria via downregulating Hexokinases II-mediated glycolysis, PUMA-mediation, which are some crucial molecules which modulate closely cancer cell growth and metastasis. Deguelin inhibits tumor cell propagation and malignant transformation through targeting angiogenesis, targeting lymphangiogenesis, targeting focal adhesion kinase (FAK), inhibiting the CtsZ/FAK signaling pathway, targeting epithelial-mesenchymal transition (EMT), the NF-kappa B signaling pathway, regulating NIMA-related kinase 2 (NEK2). In addition, deguelin possesses other biological activities, such as targeting cell cycle arrest, modulation of autophagy, inhibition of hedgehog pathway, inducing differentiation of mutated NPM1 acute myeloid leukemia etc. Therefore, deguelin is a promising chemopreventive agent for cancer therapy.	[Lin, Zhu Yue; Wu, Liu; Zhang, Tian Wen; Yao, Tang Ze] Dalian Med Univ, Pharmacol Dept, 9 West Sect,South Rd Lvshun, Dalian 116044, Liaoning, Peoples R China; [Yun, Qu Zhen; Wu, Liu; Zhang, Tian Wen] Dalian Med Univ, Pathophysiol Dept, Dalian 116044, Liaoning, Peoples R China		Yao, TZ (corresponding author), Dalian Med Univ, Pharmacol Dept, 9 West Sect,South Rd Lvshun, Dalian 116044, Liaoning, Peoples R China.	tangzeyao411@dmu.edu.com					Aggarwal B, 2013, CURR COLORECT CANC R, V9, P37, DOI 10.1007/s11888-012-0154-1; An H., J MED CHEM, V61, P9266; Baba Y, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18020262; Baba Y, 2015, BIOMED RES INT, V2015, DOI 10.1155/2015/657179; Bilecova-Rabajdova M, 2013, CENT EUR J PUBL HEAL, V21, P213, DOI 10.21101/cejph.a3886; Boreddy SR, 2013, ONCOGENE, V32, P3980, DOI 10.1038/onc.2012.413; Bundela S, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0141719; Caboni P, 2004, CHEM RES TOXICOL, V17, P1540, DOI 10.1021/tx049867r; Cao Jian-ping, 2015, Zhejiang Da Xue Xue Bao Yi Xue Ban, V44, P204; Carpenter EL, 2019, MOL CARCINOGEN, V58, P1680, DOI 10.1002/mc.23068; Chang DJ, 2012, J MED CHEM, V55, P10863, DOI 10.1021/jm301488q; Chen Hong-Bo, 2013, Zhonghua Nan Ke Xue, V19, P501; Chen LB, 2019, CANCER MANAG RES, V11, P95, DOI 10.2147/CMAR.S169476; Dal Piaz F, 2015, PLANTA MED, V81, P1223, DOI 10.1055/s-0035-1546251; Dell'Eva R, 2007, CARCINOGENESIS, V28, P404, DOI 10.1093/carcin/bgl162; Fan Yu-Lin, 2017, Nan Fang Yi Ke Da Xue Xue Bao, V37, P1545; Gao F, 2020, CELL DEATH DIS, V11, DOI 10.1038/s41419-020-2344-0; Ghanbari P, 2014, APPL BIOCHEM BIOTECH, V174, P667, DOI 10.1007/s12010-014-1125-6; Hong SJ, 2020, BIOMEDICINES, V8, DOI 10.3390/biomedicines8100407; Hsu YC, 2017, ENVIRON TOXICOL, V32, P84, DOI 10.1002/tox.22214; Hu J, 2010, INT J CANCER, V127, P2455, DOI 10.1002/ijc.25253; Hyun SY, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-32196-6; J.A. 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Res.	DEC	2021	174								105935	10.1016/j.phrs.2021.105935		OCT 2021	13	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	XG4GQ	WOS:000724713300003	34644595				2022-04-25	
J	Huang, KT; Kuo, IY; Tsai, MC; Wu, CH; Hsu, LW; Chen, LY; Kung, CP; Cheng, YF; Goto, S; Chou, YW; Chen, CL; Lin, CC; Chen, KD				Huang, Kuang-Tzu; Kuo, I-Ying; Tsai, Ming-Chao; Wu, Chun-Hsien; Hsu, Li-Wen; Chen, Li-Yu; Kung, Chao-Pin; Cheng, Yu-Fan; Goto, Shigeru; Chou, Yu-Wei; Chen, Chao-Long; Lin, Chih-Che; Chen, Kuang-Den			Factor VII-Induced MicroRNA-135a Inhibits Autophagy and Is Associated with Poor Prognosis in Hepatocellular Carcinoma	MOLECULAR THERAPY-NUCLEIC ACIDS			English	Article							PROTEASE-ACTIVATED RECEPTOR-2; CELL-PROLIFERATION; BETA-CATENIN; COLON-CANCER; EXPRESSION; LIVER; PHOSPHORYLATION; TRANSFORMATION; PROGRESSION; SUPPRESSOR	Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignancies worldwide. Treatment outcomes remain poor mainly due to lack of good diagnostic/prognostic markers and limited therapeutic strategies. We previously characterized aberrant activation of the TF/FVII/PAR2 pathway, which subsequently results in decreased autophagy, as a crucial event in malignant progression of HCC. Here, we identified miR-135a as a highly upregulated miRNA in HCC in response to TF/FVII/PAR2 activation. Analyzing 103 HCC patient specimens, we confirmed that miR-135a was frequently elevated in HCC tissues with higher FVII expression compared to adjacent non-cancerous counterparts. Increased miR-135a levels in HCC were also associated with tumor staging, recurrence, microvascular invasion, and decreased disease-free survival. We subsequently identified Atg14, a key component that regulates the formation of auto-phagosome as a direct target of miR-135a. Ectopic expression of miR-135a suppressed Atg14 levels and inhibited the autophagic processes. Our results indicate strong positive correlations between miR-135a levels and malignant behaviors in HCC patients and also suggest novel functions of miR-135a in regulation of autophagy, which could be useful as a potential target for prognostic and therapeutic uses.	[Huang, Kuang-Tzu; Kung, Chao-Pin; Chen, Chao-Long; Chen, Kuang-Den] Kaohsiung Chang Gung Mem Hosp, Inst Translat Res Biomed, 123 Da Pi Rd, Kaohsiung 83301, Taiwan; [Huang, Kuang-Tzu; Kuo, I-Ying; Wu, Chun-Hsien; Hsu, Li-Wen; Chen, Li-Yu; Kung, Chao-Pin; Chen, Chao-Long; Lin, Chih-Che; Chen, Kuang-Den] Kaohsiung Chang Gung Mem Hosp, Dept Surg, Liver Transplantat Ctr, 123 Da Pi Rd, Kaohsiung 83301, Taiwan; [Tsai, Ming-Chao] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Hepatogastroenterol, Kaohsiung 83301, Taiwan; [Cheng, Yu-Fan] Kaohsiung Chang Gung Mem Hosp, Dept Diagnost Radiol, Kaohsiung 83301, Taiwan; [Goto, Shigeru] Fukuoka Inst Occupat Hlth, Fukuoka 8150081, Japan; [Chou, Yu-Wei] Kaohsiung Chang Gung Mem Hosp, Tissue Bank, Kaohsiung 83301, Taiwan; [Chou, Yu-Wei] Kaohsiung Chang Gung Mem Hosp, BioBank, Kaohsiung 83301, Taiwan		Chen, KD (corresponding author), Kaohsiung Chang Gung Mem Hosp, Inst Translat Res Biomed, 123 Da Pi Rd, Kaohsiung 83301, Taiwan.; Lin, CC; Chen, KD (corresponding author), Kaohsiung Chang Gung Mem Hosp, Dept Surg, Liver Transplantat Ctr, 123 Da Pi Rd, Kaohsiung 83301, Taiwan.	immunologylin@gmail.com; dennis8857@gmail.com	Tsai, Ming Chao/ABA-9806-2020; Kuo, I-Ying/AAE-4741-2020	, Ming-Chao/0000-0002-3613-2051	Ministry of Science and Technology of TaiwanMinistry of Science and Technology, Taiwan [MOST 104-2314-B-182A-018, MOST 105-2314-B-182A-037-MY2, MOST 104-2314-B-182A-089-MY3]; Chang Gung Memorial HospitalChang Gung Memorial Hospital [CMRPG8C1151, CMRPG8D1032, CMRPG8D1033, CMRPG8D0561, CMRPG8D0751, CMRPG8D1022, CMRPG8D1023, CMRPG8A1203, CMRPG8E1651, CMRPG8C0952, CMRPG8D1012]; Tissue Bank Core Lab at Kaohsiung Chang Gung Memorial HospitalChang Gung Memorial Hospital [CLRPG8B0033, CLRPG8E0161, CMRPG8D0062]	This work was supported by grants from the following sources: Ministry of Science and Technology of Taiwan (MOST 104-2314-B-182A-018 and MOST 105-2314-B-182A-037-MY2 to C.-L.C. and MOST 104-2314-B-182A-089-MY3 to Y.-F.C.) and Chang Gung Memorial Hospital (CMRPG8C1151, CMRPG8D1032, and CMRPG8D1033 to K.-T.H.; CMRPG8D0561, CMRPG8D0751, CMRPG8D1022, and CMRPG8D1023 to K.-D.C.; CMRPG8A1203 and CMRPG8E1651 to C.-C.L.; and CMRPG8C0952 and CMRPG8D1012 to C.-L.C.). We also thank the Tissue Bank Core Lab at Kaohsiung Chang Gung Memorial Hospital (CLRPG8B0033, CLRPG8E0161, and CMRPG8D0062 to Y.-W.C.) for excellent technical support.	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Ther.-Nucl. Acids	DEC 15	2017	9						274	283		10.1016/j.omtn.2017.10.002			10	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	FQ6SJ	WOS:000418494000026	29246306	Green Published, gold			2022-04-25	
J	Thoresen, SB; Pedersen, NM; Liestol, K; Stenmark, H				Thoresen, Sigrid B.; Pedersen, Nina Marie; Liestol, Knut; Stenmark, Harald			A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic	EXPERIMENTAL CELL RESEARCH			English	Article						Endocytosis; Cytokinesis; Autophagy; PI 3-kinase; Tumor suppressor	TUMOR-SUPPRESSOR; EARLY ENDOSOMES; MICROSATELLITE INSTABILITY; PROMOTES TUMORIGENESIS; MEMBRANE CURVATURE; AUTOPHAGY GENE; COLON-CANCER; PROTEINS; CELLS; ESCRT	The mammalian class III phosphatidylinositol 3-kinase (PI3K-III) complex regulates fundamental cellular functions, including growth factor receptor degradation, cytokinesis and autophagy. Recent studies suggest the existence of distinct PI3K-III sub-complexes that can potentially confer functional specificity. While a substantial body of work has focused on the roles of individual PI3K-III subunits in autophagy, functional studies on their contribution to endocytic receptor downregulation and cytokinesis are limited. We therefore sought to elucidate the specific nature of the PI3K-III complexes involved in these two processes. High-content microscopy-based assays combined with siRNA-mediated depletion of individual subunits indicated that a specific sub-complex containing VPS15, VP534, Beclin 1, UVRAG and BIF-1 regulates both receptor degradation and cytokinesis, whereas ATG14L, a PI3K-III subunit involved in autophagy, is not required. The unanticipated role of UVRAG and BIF-1 in cytokinesis was supported by a strong localisation of these proteins to the midbody. Importantly, while the tumour suppressive functions of Beclin 1, UVRAG and BIF-1 have previously been ascribed to their roles in autophagy, these results open the possibility that they may also contribute to tumour suppression via downregulation of mitogenic signalling by growth factor receptors or preclusion of aneuploidy by ensuring faithful completion of cell division. (C) 2010 Elsevier Inc. All rights reserved.	[Thoresen, Sigrid B.; Pedersen, Nina Marie; Liestol, Knut; Stenmark, Harald] Univ Oslo, Ctr Canc Biomed, Fac Med, N-0310 Oslo, Norway; [Thoresen, Sigrid B.; Pedersen, Nina Marie; Stenmark, Harald] Oslo Univ Hosp, Dept Biochem, Inst Canc Res, Norwegian Radium Hosp, N-0310 Oslo, Norway		Stenmark, H (corresponding author), Univ Oslo, Ctr Canc Biomed, Fac Med, N-0310 Oslo, Norway.	sigrid.thoresen@rr-research.no; Nina.Marie.Pedersen@rr-research.no; knut@ifi.uio.no; stenmark@ulrik.uio.no	Stenmark, Harald/B-8868-2008		South-Eastern Norway Health Authority; Research Council of NorwayResearch Council of Norway; European Research CouncilEuropean Research Council (ERC)European Commission; Norwegian Cancer SocietyNorwegian Cancer Society	The authors thank Prof. T. Yoshimori and Dr. N. Mizushima for providing anti-ATG14L antibodies. The work presented in this study was supported by funds from the South-Eastern Norway Health Authority, the Research Council of Norway, the European Research Council, and the Norwegian Cancer Society.	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J	Lv, C; Zeng, HW; Wang, JX; Yuan, X; Zhang, C; Fang, T; Yang, PM; Wu, T; Zhou, YD; Nagle, DG; Zhang, WD				Lv, Chao; Zeng, Hua-Wu; Wang, Jin-Xin; Yuan, Xing; Zhang, Chuang; Fang, Ting; Yang, Pei-Ming; Wu, Tong; Zhou, Yu-Dong; Nagle, Dale G.; Zhang, Wei-Dong			The antitumor natural product tanshinone IIA inhibits protein kinase C and acts synergistically with 17-AAG	CELL DEATH & DISEASE			English	Article							DRUG TARGET ENGAGEMENT; PROSTATE-CANCER CELLS; THERMAL SHIFT ASSAY; BREAST-CANCER; IN-VIVO; PKC ISOFORMS; PI3K/AKT/MTOR PATHWAY; MOLECULAR TARGETS; CONNECTIVITY MAP; COLON-CARCINOMA	Tanshinone IIA (Tan IIA), the primary bioactive compound derived from the traditional Chinese medicine (TCM) Salvia miltiorrhiza Bunge, has been reported to possess antitumor activity. However, its antitumor mechanisms are not fully understood. To resolve the potential antitumor mechanism(s) of Tan IIA, its gene expression profiles from our database was analyzed by connectivity map (CMAP) and the CMAP-based mechanistic predictions were confirmed/validated in further studies. Specifically, Tan IIA inhibited total protein kinase C (PKC) activity and selectively suppressed the expression of cytosolic and plasma membrane PKC isoforms zeta and epsilon. The Ras/MAPK pathway that is closely regulated by the PKC signaling is also inhibited by Tan IIA. While Tan IIA did not inhibit heat shock protein 90 (Hsp90), it synergistically enhanced the antitumor efficacy of the Hsp90 inhibitors 17-AAG and ganetespib in human breast cancer MCF-7 cells. In addition, Tan IIA significantly inhibited PI3K/Akt/mTOR signaling, and induced both cell cycle arrest and autophagy. Collectively, these studies provide new insights into the molecular mechanisms responsible for antitumor activity of Tan IIA.	[Lv, Chao; Yang, Pei-Ming; Wu, Tong; Zhang, Wei-Dong] China State Inst Pharmaceut Ind, Shanghai Inst Pharmaceut Ind, Shanghai 201203, Peoples R China; [Zeng, Hua-Wu; Wang, Jin-Xin; Yuan, Xing; Zhang, Wei-Dong] Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China; [Zhang, Chuang] Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Henan, Peoples R China; [Fang, Ting] Fujian Univ Tradit Chinese Med, Sch Pharm, Fuzhou 350108, Fujian, Peoples R China; [Zhou, Yu-Dong; Nagle, Dale G.] Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Biomed Res, Shanghai 201203, Peoples R China; [Zhou, Yu-Dong] Univ Mississippi, Dept Chem & Biochem, Coll Liberal Arts, University, MS 38677 USA; [Nagle, Dale G.] Univ Mississippi, Sch Pharm, Dept Biomol Sci, University, MS 38677 USA; [Nagle, Dale G.] Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, University, MS 38677 USA		Zhang, WD (corresponding author), China State Inst Pharmaceut Ind, Shanghai Inst Pharmaceut Ind, Shanghai 201203, Peoples R China.; Zhang, WD (corresponding author), Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China.	wdzhangy@hotmail.com		Nagle, Dale/0000-0001-7883-2673	Professor of Chang Jiang Scholars Program, NSFC [81230090, 81520108030, 21472238, 81602980]; Shanghai Engineering Research Center for the Preparation of Bioactive Natural Products [16DZ2280200]; Scientific Foundation of Shanghai China [12401900801, 13401900103, 13401900101]; National Major Project of China [2011ZX09307002-03]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [CA199016]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R15CA199016] Funding Source: NIH RePORTER	The work was supported by Professor of Chang Jiang Scholars Program, NSFC (81230090, 81520108030, 21472238, 81602980), Shanghai Engineering Research Center for the Preparation of Bioactive Natural Products (16DZ2280200), the Scientific Foundation of Shanghai China (12401900801, 13401900103, 13401900101), National Major Project of China (2011ZX09307002-03), Y.D.Z is in part supported by NIH grant CA199016.	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FEB 7	2018	9								165	10.1038/s41419-017-0247-5			13	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	FZ2IN	WOS:000427401400007	29416003	Green Published, gold			2022-04-25	
J	Jara, JA; Lopez-Munoz, R				Jara, J. A.; Lopez-Munoz, R.			Metformin and cancer: Between the bioenergetic disturbances and the antifolate activity	PHARMACOLOGICAL RESEARCH			English	Review						Cancer; Chemotherapy; Mitochondria; Metformin; Complex I; Folate cycle; Nucleotides	MESENCHYMAL TRANSITION EMT; TYPE-2 DIABETES-MELLITUS; ACTIVATED PROTEIN-KINASE; CELL-CYCLE ARREST; BREAST-CANCER; MAMMALIAN TARGET; VITAMIN-B-12 DEFICIENCY; HOMOCYSTEINE LEVELS; COLON-CANCER; STEM-CELLS	For decades, metformin has been the first-line drug for the treatment of type II diabetes mellitus, and it thus is the most widely prescribed antihyperglycemic drug. Retrospective studies associate the use of metformin with a reduction in cancer incidence and cancer-related death. However, despite extensive research about the molecular effects of metformin in cancer cells, its mode of action remains controversial. In this review, we summarize the current molecular evidence in an effort to elucidate metformin's mode of action against cancer cells. Some authors describe that metformin acts directly on mitochondria, inhibiting complex I and restricting the cell's ability to cope with energetic stress. Furthermore, as the drug interrupts the tricarboxylic acid cycle, metformin-induced alteration of mitochondrial function leads to a compensatory increase in lactate and glycolytic ATP. It has also been reported that cell cycle arrest, autophagy, apoptosis and cell death induction is mediated by the activation of AMPK and Redd1 proteins, thus inhibiting the mTOR pathway. Additionally, unbiased metabolomics studies have provided strong evidence to support that metformin alters the methionine and folate cycles, with a concomitant decrease in nucleotide synthesis. Indeed, purines such as thymidine or hypoxanthine restore the proliferation of tumor cells treated with metformin in vitro. Consequently, some authors prefer to refer to metformin as an "antimetabolite drug" rather than a "mitochondrial toxin". Finally, we also review the current controversy concerning the relationship between the experimental conditions of in vitro-reported effects and the plasma concentrations achieved by chronic treatment with metformin. (c) 2015 Elsevier Ltd. All rights reserved.	[Jara, J. A.] Univ Chile, Fac Odontol, ICOD, Unidad Farmacol & Farmacogenet, Santiago, Chile; [Lopez-Munoz, R.] Univ Austral Chile, Fac Ciencias Vet, Inst Farmacol & Morfofisiol, Valdivia, Chile		Lopez-Munoz, R (corresponding author), Univ Austral Chile, Fac Ciencias Vet, Inst Farmacol & Morfofisiol, Campus Isla Teja S-N,POB 5090000, Valdivia, Chile.	rodrigo.lopez@uach.cl	Jara, Jose/K-1936-2014; Lopez-Muñoz, Rodrigo/I-1097-2013	Lopez-Muñoz, Rodrigo/0000-0003-1825-8563	Vicerrectoria de Investigacion, Universidad de Chile [156]; Consejo Nacional de Investigaciones Cientificas y Tecnologicas-CONICYT, Chile [791220004]; Direccion de Investigacion, Universidad Austral de Chile [S-2015-05]	JAJ is supported by the grants U-INICIA #156 (Vicerrectoria de Investigacion, Universidad de Chile) and "Proyecto de Insercion en la Academia" #791220004 (Consejo Nacional de Investigaciones Cientificas y Tecnologicas-CONICYT, Chile). RLM is supported by the grant DID-UACh #S-2015-05 (Direccion de Investigacion, Universidad Austral de Chile).	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Res.	NOV	2015	101				SI		102	108		10.1016/j.phrs.2015.06.014			7	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	CV4TF	WOS:000364258700012	26277279				2022-04-25	
J	Yan, YM; Jiang, K; Liu, P; Zhang, XB; Dong, X; Gao, JC; Liu, QT; Barr, MP; Zhang, Q; Hou, XK; Meng, SS; Gong, P				Yan, Yumei; Jiang, Ke; Liu, Peng; Zhang, Xianbin; Dong, Xin; Gao, Jingchun; Liu, Quentin; Barr, Martin P.; Zhang, Quan; Hou, Xiukun; Meng, Songshu; Gong, Peng			Bafilomycin A1 induces caspase-independent cell death in hepatocellular carcinoma cells via targeting of autophagy and MAPK pathways	SCIENTIFIC REPORTS			English	Article							VACUOLAR H+-ATPASE; COLON-CANCER CELLS; CYCLIN D1; INHIBITION; APOPTOSIS; GROWTH; LINE	Hepatocellular carcinoma (HCC) is refractory to chemotherapies, necessitating novel effective agents. The lysosome inhibitor Bafilomycin A1 (BafA1) at high concentrations displays cytotoxicity in a variety of cancers. Here we show that BafA1 at nanomolar concentrations suppresses HCC cell growth in both 2 dimensional (2D) and 3D cultures. BafA1 induced cell cycle arrest in the G1 phase and triggered Cyclin D1 turnover in HCC cells in a dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) dependent manner. Notably, BafA1 induced caspase-independent cell death in HCC cells by impairing autophagy flux as demonstrated by elevated LC3 conversion and p62/SQSTM1 levels. Moreover, genetic ablation of LC3 significantly attenuated BafA1-induced cytotoxicity of HCC cells. We further demonstrate that pharmacological down-regulation or genetic depletion of p38 MAPK decreased BafA1-induced cell death via abolishment of BafA1-induced upregulation of Puma. Notably, knockdown of Puma impaired BafA1-induced HCC cell death, and overexpression of Puma enhanced BafA1-mediated HCC cell death, suggesting a role for Puma in BafA1-mediated cytotoxicity. Interestingly, pharmacological inhibition of JNK with SP600125 enhanced BafA1-mediated cytotoxicity both in vitro and in xenografts derived from HCC cells. Taken together, our data suggest that BafA1 may offer potential as an effective therapy for HCC.	[Yan, Yumei; Liu, Peng; Zhang, Xianbin; Dong, Xin; Gao, Jingchun; Gong, Peng] Dalian Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, 222 Zhongshan Rd, Dalian 116021, Peoples R China; [Yan, Yumei; Hou, Xiukun] Dalian Med Univ, Dept Ultrasound 1, Affiliated Hosp 1, 222 Zhongshan Rd, Dalian 116021, Peoples R China; [Jiang, Ke; Liu, Quentin; Meng, Songshu] Dalian Med Univ, Ctr Canc, Inst Canc Stem Cell, 9 Lvshun Rd South, Dalian 116044, Peoples R China; [Barr, Martin P.] St James Hosp, Trinity Ctr Hlth Sci, Trinity Translat Med Inst, Thorac Oncol Res Grp, Dublin, Ireland; [Barr, Martin P.] Trinity Coll Dublin, Dublin, Ireland; [Zhang, Quan] Yangzhou Univ, Coll Vet Med, Yangzhou 225009, Jiangsu, Peoples R China; [Yan, Yumei; Gong, Peng] Dalian Key Lab Hepatobiliary Pancreat Dis Prevent, Dalian 116021, Peoples R China; [Yan, Yumei] Dalian Med Univ, Grad Sch, 9 Lvshun Rd South, Dalian 116044, Peoples R China		Gong, P (corresponding author), Dalian Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, 222 Zhongshan Rd, Dalian 116021, Peoples R China.; Hou, XK (corresponding author), Dalian Med Univ, Dept Ultrasound 1, Affiliated Hosp 1, 222 Zhongshan Rd, Dalian 116021, Peoples R China.; Meng, SS (corresponding author), Dalian Med Univ, Ctr Canc, Inst Canc Stem Cell, 9 Lvshun Rd South, Dalian 116044, Peoples R China.; Gong, P (corresponding author), Dalian Key Lab Hepatobiliary Pancreat Dis Prevent, Dalian 116021, Peoples R China.	xiukunhou28@sina.com; ssmeng@dmu.edu.cn; gongpengdalian@163.com		Barr, Martin/0000-0001-5202-9655; Zhang, Xianbin/0000-0002-0948-6698	National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572707, 81473504, 81502674]; Liaoning Provincial Science and Technology Plan Project [201202051]; Program for Liaoning Excellent Talents in University [LR2015018]	We thank Tamotsu Yoshimori (Osaka University, Osaka, Japan) for the GFP-mRFP-LC3 plasmid. This work was supported by grants from the National Science Foundation of China (81572707 to SM, 81473504 to PG, 81502674 to KJ) and Liaoning Provincial Science and Technology Plan Project (201202051 to XH). Program for Liaoning Excellent Talents in University (LR2015018 to PG).	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J	Yang, L; Liu, YQ; Wang, M; Qian, YY; Dai, XJ; Zhu, YD; Chen, J; Guo, SY; Hisamitsu, T				Yang, Lin; Liu, Yanqing; Wang, Mei; Qian, Yayun; Dai, Xiaojun; Zhu, Yaodong; Chen, Jue; Guo, Shiyu; Hisamitsu, Tadashi			Celastrus orbiculatus extract triggers apoptosis and autophagy via PI3K/Akt/mTOR inhibition in human colorectal cancer cells	ONCOLOGY LETTERS			English	Article						Celastrus orbiculatus extract; autophagy; apoptosis	SIGNALING PATHWAY; MAMMALIAN TARGET; SELF-DIGESTION; BCL-2 FAMILY; IN-VITRO; DISEASE; DEATH; ANGIOGENESIS; CONSTITUENTS; MECHANISMS	Celastrus orbiculatus is used as a folk medicine in China for the treatment of numerous diseases. The ethyl acetate extract of Celastrus orbiculatus (COE) also displays a wide range of anti-cancer activities in the laboratory. However, the effectiveness of COE-induced autophagy and its mechanism of action in colorectal cancer cells have not been investigated thus far. The present study analyzed the effect of COE on HT-29 cell viability, apoptosis and autophagy using MTT assay, flow cytometry, transmission electron microscopy and western blotting. Additionally, the autophagy inhibitor 3-methyladenine and the autophagy inducer rapamycin were used to further explore the effects of COE-induced autophagy in HT-29 cells. The present study also examined whether the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) signaling pathway was involved in the regulation of COE-induced autophagy. The results revealed that COE inhibited HT-29 cell proliferation and decreased cell survival in a time- and dose-dependent manner, and that COE possessed the ability to induce both apoptosis and autophagy in HT-29 cells. Furthermore, autophagy and apoptosis induced by COE synergized to inhibit colorectal cancer growth. In addition, COE treatment decreased the phosphorylation of Akt and its downstream effectors mTOR and p70S6K. Taken together, these results demonstrate that both autophagy and apoptosis were activated during COE treatment of HT-29 cells, and that COE-induced autophagy decreases the viability of HT-29 cells via a mechanism that may depend on the PI3K/Akt/mTOR/p70S6K signaling pathway. Furthermore, compounds that induce autophagy administered in combination with COE may be an attractive strategy for enhancing the anti-tumor potency of COE in colorectal cancer.	[Yang, Lin; Liu, Yanqing; Wang, Mei; Qian, Yayun; Dai, Xiaojun; Zhu, Yaodong; Chen, Jue] Yangzhou Univ, Inst Tradit Chinese Med & Western Med, Sch Med, 11 Huaihai Rd, Yangzhou 225009, Jiangsu, Peoples R China; [Yang, Lin; Liu, Yanqing; Qian, Yayun; Dai, Xiaojun; Zhu, Yaodong; Chen, Jue] Jiangsu Key Lab Integrated Tradit Chinese & Weste, Yangzhou 225001, Jiangsu, Peoples R China; [Yang, Lin; Liu, Yanqing; Qian, Yayun; Dai, Xiaojun; Zhu, Yaodong; Chen, Jue] Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Jiangsu, Peoples R China; [Wang, Mei] Yangzhou Univ, Dept Gastroenterol, Peoples Hosp Yangzhou 1, Sch Clin 2, Yangzhou 225000, Jiangsu, Peoples R China; [Guo, Shiyu; Hisamitsu, Tadashi] Showa Univ, Sch Med, Dept Physiol, Tokyo 1428555, Japan		Liu, YQ (corresponding author), Yangzhou Univ, Inst Tradit Chinese Med & Western Med, Sch Med, 11 Huaihai Rd, Yangzhou 225009, Jiangsu, Peoples R China.	liuyanqing2014@163.com			National Natural Science Foundation of China (Beijing, China)National Natural Science Foundation of China (NSFC) [81403232, 81274141, 81450051]; Natural Science Foundation of Jiangsu Province of China (Nanjing, China) [BK 2012686, SBK 2014021480]	The present study was financially supported by grants from the National Natural Science Foundation of China (Beijing, China; grant nos. 81403232, 81274141 and 81450051) and the Natural Science Foundation of Jiangsu Province of China (Nanjing, China; grant nos. BK 2012686 and SBK 2014021480).	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D., 2014, CHIN J INTEGR MED, DOI [10.1007/s11655-014-1951-y, DOI 10.1007/S11655-014-1951-Y]; Zhu YD, 2015, INTEGR CANCER THER, V14, P271, DOI 10.1177/1534735415572880	39	33	42	0	13	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1792-1074	1792-1082		ONCOL LETT	Oncol. Lett.	NOV	2016	12	5					3771	3778		10.3892/ol.2016.5213			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	ED4RR	WOS:000388838900108	27895729	Green Submitted, Green Published, gold			2022-04-25	
J	Pan, TH; Liu, JW; Xu, S; Yu, Q; Wang, HP; Sun, HX; Wu, J; Zhu, Y; Zhou, JW; Zhu, YL				Pan, Tianhui; Liu, Jingwen; Xu, Song; Yu, Qiao; Wang, Hongping; Sun, Hongxiang; Wu, Jia; Zhu, Yue; Zhou, Jianwei; Zhu, Yongliang			ANKRD22, a novel tumor microenvironment-induced mitochondrial protein promotes metabolic reprogramming of colorectal cancer cells	THERANOSTICS			English	Article						Colorectal cancer; Tumor microenvironment; Cancer-initiating cells; ANKRD22; Metabolic reprogramming	STEM-CELLS; GLYCOLYSIS; PLURIPOTENCY; PLASTICITY; CARCINOMA; MARKERS	Background: The leading cause of poor prognosis in colorectal cancer (CRC) is the presence of colorectal cancer-initiating cells (CCICs). The interplay between the tumor microenvironment (TME) and CRC cells induces reacquisition of initiating cell characteristics, but the underlying mechanisms remain elusive. Methods: Candidate molecules were screened by global differential cDNA expression profiles of CCICs, which were enriched from patient-derived tumor xenograft models. Luciferase reporters and chromatin immunoprecipitation assays were used to explore the mechanism of TME factors regulating the transcription of ANKRD22. The effects of Ankyrin repeat domain-containing protein 22 (ANKRD22) on energy metabolism were monitored by extracellular flux and C-13-based metabolic flux analysis. Mass spectrometry was used to identify the interacting partners of ANKRD22. Morphological changes of CCICs overexpressing ANKRD22 were observed by electron microscopy. The effects of ANKRD22 on mitochondrial lipid metabolism were analyzed by lipidomics. Results: We identified a novel nucleus-encoded mitochondrial membrane protein, ANKRD22, which was upregulated in CCICs. We found that ANKRD22 was induced by the p38/MAX pathway activated by different TME stimuli. As a key transcription factor, MAX promoted the transcription of ANKRD22. Expression of ANKRD22 promoted glycolysis associated with a decrease in ATP/ADP and an increase in AMP/ATP levels, which were related to its interaction with pyruvate dehydrogenase kinase isoform 1 (PDK1) and multiple subunits of ATP synthase. Further, in CCICs, ANKRD22 cooperated with the lipid transport protein, Extended Synaptotagmin-1 (E-Syt1), to transport excess lipids into mitochondria and reduced the number of mitochondria in an autophagy-independent manner, thus meeting the metabolic requirements of CCICs. Conclusion: ANKRD22 induced by TME promotes the metabolic reprogramming of CRC cells. Our study has identified ANKRD22/E-Syt1 as a potential target for eradicating CCICs.	[Pan, Tianhui; Liu, Jingwen; Xu, Song; Yu, Qiao; Wang, Hongping; Wu, Jia; Zhu, Yongliang] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Lab Gastroenterol Dept, Hangzhou 310009, Zhejiang, Peoples R China; [Zhou, Jianwei] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Gynecol, Hangzhou 310009, Zhejiang, Peoples R China; [Sun, Hongxiang] Zhejiang Univ, Coll Anim Sci, Lab Nat Drug, Hangzhou 310058, Zhejiang, Peoples R China; [Zhu, Yongliang] Key Lab Tumor Microenviroment & Immune Therapy Zh, Hangzhou 310009, Zhejiang, Peoples R China; [Zhu, Yue] Wenzhou Med Univ, Coll Stormotologry, Wenzhou 325035, Zhejiang, Peoples R China		Zhu, YL (corresponding author), Zhejiang Univ, Sch Med, Affiliated Hosp 2, Lab Gastroenterol Dept, Hangzhou 310009, Zhejiang, Peoples R China.; Zhou, JW (corresponding author), Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Gynecol, Hangzhou 310009, Zhejiang, Peoples R China.	2195045@zju.edu.cn; ylzhu@zju.edu.cn			National Science of Foundation Committee of China [81672898, 81472723, 81602584, 81700455]	We thank Ms. Dong Qi at Cancer Institute of Zhejiang University for her excellent skills in Confocal microscopy. This work was supported by grants from the National Science of Foundation Committee of China (81672898, 81472723, 81602584 and 81700455).	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J	Yang, J; Jiang, H; Wang, CY; Yang, B; Zhao, LJ; Hu, DL; Qiu, GH; Dong, XL; Xiao, B				Yang, Jie; Jiang, Hai; Wang, Chunyu; Yang, Bo; Zhao, Lijun; Hu, Dongling; Qiu, Guihua; Dong, Xiaolin; Xiao, Bin			Oridonin triggers apoptosis in colorectal carcinoma cells and suppression of microRNA-32 expression augments oridonin-mediated apoptotic effects	BIOMEDICINE & PHARMACOTHERAPY			English	Article						Oridonin; Colorectal carcinoma cells; Apoptosis; MicroRNA-32; Caspase-3; Caspase-9	CANCER-CELLS; GLUTATHIONE DEPLETION; MITOCHONDRIAL PATHWAY; GROWTH-INHIBITION; UP-REGULATION; PROLIFERATION; LINE; STATISTICS; MECHANISM; AUTOPHAGY	Oridonin, a bioactive diterpenoid isolated from Rabdosia rubescens, has been found to exhibit various anti-tumor effects. In this work, to investigate its pharmacological effects on human colorectal carcinoma HCT-116 and LoVo cells, cell proliferation and apoptosis were respectively evaluated by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, annexin V-FITC, and propidium iodide (PI) staining. Western blotting was used to detect the expression levels of Bim, Bax, Bcl-2, cytosolic cytochrome c, procaspase-9, cleaved caspase-9, procaspase-3, and caspase-3 proteins. Caspase-Glo-9 and Caspase-Glo-3 assays were applied to determine caspase-9 and caspase-3 activity. MicroRNA-32 (miR-32) expression level was detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The in vivo anti-tumor effects of oridonin were evaluated using cell lines HCT-116 and LoVo xenograft model. The results indicated that oridonin effectively inhibited cell proliferation and induced apoptosis in HCT-116 and LoVo cells in a concentration-dependent manner. Oridonin treatment upregulated the expression levels of Bim, Bax, cytosolic cytochrome c, cleaved caspase-9 and cleaved caspase-3 proteins, downregulated the expression levels of Bcl-2, procaspase-9 and procaspase-3 proteins, and meanwhile obviously activated caspase-9 and caspase-3 in a dose-dependent manner in HCT-116 and LoVo cells. The results of qRT-PCR demonstrated that oridonin treatment significantly decreased miR-32 expression, and furthermore, suppression of miR-32 expression by miR-32 inhibitors augmented oridonin-mediated inhibitory and apoptotic effects in HCT-116 and LoVo cells. In vivo results indicated that oridonin administration through intraperitoneal injection suppressed tumor growth in nude mice. Therefore, these findings suggest that oridonin maybe is a potential candidate for colorectal cancer treatment. (C) 2015 Elsevier Masson SAS. All rights reserved.	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J	Kaistha, BP; Lorenz, H; Schmidt, H; Sipos, B; Pawlak, M; Gierke, B; Kreider, R; Lankat-Buttgereit, B; Sauer, M; Fiedler, L; Krattenmacher, A; Geisel, B; Kraus, JM; Frese, KK; Kelkenberg, S; Giese, NA; Kestler, HA; Gress, TM; Buchholz, M				Kaistha, Brajesh P.; Lorenz, Holger; Schmidt, Harald; Sipos, Bence; Pawlak, Michael; Gierke, Berthold; Kreider, Ramona; Lankat-Buttgereit, Brigitte; Sauer, Melanie; Fiedler, Lisa; Krattenmacher, Anja; Geisel, Bettina; Kraus, Johann M.; Frese, Kristopher K.; Kelkenberg, Sabine; Giese, Nathalia A.; Kestler, Hans A.; Gress, Thomas M.; Buchholz, Malte			PLAC8 Localizes to the Inner Plasma Membrane of Pancreatic Cancer Cells and Regulates Cell Growth and Disease Progression through Critical Cell-Cycle Regulatory Pathways	CANCER RESEARCH			English	Article							FLUORESCENCE PROTEASE PROTECTION; SUBCELLULAR-LOCALIZATION; LIVING CELLS; COLON-CANCER; EXPRESSION; ONZIN; MICE; DIFFERENTIATION; MICROARRAY; APOPTOSIS	Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumors and is generally strongly resistant to currently available chemo- and/or radiotherapy regimens, including targeted molecular therapies. Therefore, unraveling the molecular mechanisms underlying the aggressive behavior of pancreatic cancer is a necessary prerequisite for the development of novel therapeutic approaches. We previously identified the protein placenta-specific 8 (PLAC8, onzin) in a genome-wide search for target genes associated with pancreatic tumor progression and demonstrated that PLAC8 is strongly ectopically expressed in advanced preneoplastic lesions and invasive human PDAC. However, the molecular function of PLAC8 remained unclear, and accumulating evidence suggested its role is highly strate that in contrast to other cellular systems, PLAC8 protein localizes to the inner face of the plasma membrane in pancreatic cancer cells, where it interacts with specific membranous structures in a temporally and spatially stable manner. Inhibition of PLAC8 expression strongly inhibited pancreatic cancer cell growth by attenuating cell-cycle progression, which was associated with transcriptional and/or posttranslational modification of the central cell-cycle regulators CDKN1A, retinoblastoma protein, and cyclin D1 (CCND1), but did not impact autophagy. Moreover, Plac8 deficiency significantly inhibited tumor formation in genetically engineered mouse models of pancreatic cancer. Together, our findings establish PLAC8 as a central mediator of tumor progression in PDAC and as a promising candidate gene for diagnostic and therapeutic targeting. (C)2015 AACR.	[Kaistha, Brajesh P.; Schmidt, Harald; Kreider, Ramona; Lankat-Buttgereit, Brigitte; Sauer, Melanie; Fiedler, Lisa; Krattenmacher, Anja; Geisel, Bettina; Gress, Thomas M.; Buchholz, Malte] Univ Marburg, Clin Gastroenterol Endocrinol Metab & Infectiol, D-35043 Marburg, Germany; [Lorenz, Holger] Univ Heidelberg ZMBH, Zentrum Mol Biol, Cent Imaging Facil, Heidelberg, Germany; [Sipos, Bence] Univ Clin Tubingen, Dept Pathol, Tubingen, Germany; [Pawlak, Michael; Gierke, Berthold] Univ Tubingen, NMI Nat & Med Sci Inst, Dept Biochem & Prot Profiling, Reutlingen, Germany; [Kraus, Johann M.; Kestler, Hans A.] Univ Ulm, Med Syst Biol, D-89069 Ulm, Germany; [Frese, Kristopher K.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada; [Kelkenberg, Sabine] CeGaT GmbH, Tubingen, Germany; [Giese, Nathalia A.] Univ Clin Heidelberg, Dept Surg, Heidelberg, Germany		Buchholz, M (corresponding author), Univ Marburg, Zentrum Tumor & Immunbiol, Hans Meerwein Str 3, D-35043 Marburg, Germany.	malte.buchholz@staff.uni-marburg.de	Kestler, Hans A./D-5799-2012; Sauer, Markus/C-4378-2017	Kestler, Hans A./0000-0002-4759-5254; Sauer, Markus/0000-0002-1692-3219; Kaistha, Brajesh Pratap/0000-0002-4071-6260; Gress, Thomas/0000-0002-9333-5461	German Research Foundation (DFG)German Research Foundation (DFG) [Bu 1536/3-1]; Heidelberger Pancobank (BMBF) [01GS08114]; BMBF grantFederal Ministry of Education & Research (BMBF) [01EY1101]; EU FP7 grant [602783]	This work was funded in part by the German Research Foundation (DFG; grant Bu 1536/3-1), Heidelberger Pancobank (BMBF grant 01GS08114), BMBF grant 01EY1101, and EU FP7 grant no. 602783 (large-scale integrated project "CAM-PaC").	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J	Fernandes, LG; Tobias, GC; Paixao, AO; Dourado, PM; Voltarelli, VA; Brum, PC				Fernandes, L. G.; Tobias, G. C.; Paixao, A. O.; Dourado, P. M.; Voltarelli, V. A.; Brum, P. C.			Exercise training delays cardiac remodeling in a mouse model of cancer cachexia	LIFE SCIENCES			English	Article						Aerobic exercise training; Cancer cachexia; Cardiac damage; Fibrosis; Inflammation; Necrosis	QUALITY-OF-LIFE; HEART-FAILURE; SYMPATHETIC HYPERACTIVITY; DYSFUNCTION; CAPACITY; MECHANISMS; BENEFITS; IMPACT; CELLS	Aims: We aimed to investigate the impact of cancer cachexia and previous aerobic exercise training (AET) on cardiac function and structure in tumor bearing mice. Main methods: Colon adenocarcinoma cells 26 (CT26) were subcutaneously injected in BALB/c mice to establish robust cancer cachexia model. AET was performed on a treadmill during 45 days, 60 min/5 days per week. Cardiac function was evaluated by echocardiography and cardiac morphology was assessed by light microscopy. The protein expression levels of mitochondrial complex were analyzed by Western blotting. The mRNA levels of genes related to cardiac remodeling and autophagy were analyzed by quantitative Real-Time PCR. Key findings: Our data confirms CT26 tumor bearing mice as a well-characterized and robust model of cancer cachexia. CT26 mice exhibited cardiac remodeling and dysfunction characterized by cardiac atrophy and impaired left ventricle ejection fraction paralleled by cardiac necrosis, inflammation and fibrosis. AET partially reversed the left ventricle ejection fraction and led to significant anti-cardiac remodeling effect associated reduced necrosis, inflammation and cardiac collagen deposition in CT26 mice. Reduced TGF-beta 1 mRNA levels, increased mitochondrial complex IV protein levels and partial recovery of BNIP3 mRNA levels in cardiac tissue were associated with the cardiac effects of AET in CT26 mice. Thus, we suggest AET as a powerful regulator of key pathways involved in cardiac tissue homeostasis in cancer cachexia. Significance: Our study provides a robust model of cancer cachexia, as well as highlights the potential and integrative effects of AET as a preventive strategy for reducing cardiac damage in cancer cachexia.	[Fernandes, L. G.] Univ Sao Paulo, Med Sch, Dept Expt Pathophysiol, Sao Paulo, Brazil; [Fernandes, L. G.; Tobias, G. C.; Paixao, A. O.; Voltarelli, V. A.; Brum, P. C.] Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil; [Dourado, P. M.] Univ Sao Paulo, Clin Hosp, Fac Med, Heart Inst, Sao Paulo, Brazil		Brum, PC (corresponding author), Univ Sao Paulo, Escola Educ Fis & Esporte, Dept Biodinam Movimento Corpo Humano, Av Prof Mello Moraes,65 Butanta, BR-05508900 Sao Paulo, SP, Brazil.	pcbrum@usp.br	Brum, Patricia C/E-6605-2011; Voltarelli, Vanessa Azevedo/AAB-8897-2021; Voltarelli, Vanessa Azevedo/J-3419-2015	Brum, Patricia C/0000-0002-4750-6506; Voltarelli, Vanessa Azevedo/0000-0003-0087-646X; Voltarelli, Vanessa Azevedo/0000-0003-0087-646X; Reis, AlessanRSS/0000-0001-8486-7469; Paixao, Ailma/0000-0003-2805-7319	Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Sao Paulo - SP (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2016/22835-5, 2014/25830-9, 2015/22814-5]; Conselho Nacional de Pesquisa e Desenvolvimento - Brasil (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [BPQ-306261/2016-2]	This work was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Sao Paulo - SP (FAPESP #2016/22835-5, #2014/25830-9, #2015/22814-5), PCB holds financial support from Conselho Nacional de Pesquisa e Desenvolvimento - Brasil (CNPq, BPQ-306261/2016-2).	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NOV 1	2020	260								118392	10.1016/j.lfs.2020.118392			12	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	OH5FK	WOS:000582605800040	32898523				2022-04-25	
J	Yang, Y; Wen, FB; Dang, LF; Fan, YX; Liu, DL; Wu, K; Zhao, S				Yang Yang; Wen Fengbiao; Dang Lifeng; Fan Yuxia; Liu Donglei; Wu Kai; Zhao Song			Insulin enhances apoptosis induced by cisplatin in human esophageal squamous cell carcinoma EC9706 cells related to inhibition of autophagy	CHINESE MEDICAL JOURNAL			English	Article						esophageal squamous cell carcinoma; insulin; chemotherapy sensitivity; autophagy; apoptosis; PI3K/Akt/mTOR signalling pathway	CANCER-THERAPY; COLON-CANCER; 5-FLUOROURACIL; TEMOZOLOMIDE; EXPRESSION; RESISTANCE; GROWTH; TUMORS	Background Chemoresistance is common among patients with esophageal squamous cell carcinoma (ESCC). We investigated the effect and mechanism of insulin on enhancing anticancer functions of cisplatin in human esophageal cancer cell line EC9706. Methods The viability of EC9706 cells exposed to cisplatin was assessed using MTT assay. The times T1, when the number of living cells reached a plateau and T2, when the number of living cells reached a new plateau after the addition of insulin were found. T1 and T2 plateau cells were stained by Annexin V-FITC/PI and monodansylcadaverin (MDC). Fluorescent microscopy was used to observe the expression of apoptosis and autophagy intuitively. Apoptotic ratio and fluorescent intensity were analysed by flow cytometry (FCM) quantitatively. Western blotting analysis was used to estimate the protein expression levels of AKT, mTOR, PI3K, PTEN, autophage related indicator LC3-II and autophage related protein Beclin1 changes that occurred in the course of treatment. Results A larger number of typical autophagosomes were detected in EC9706 cells exposed to cisplatin. Insulin can increase the apoptosis induced by cisplatin. Apoptotic ratio of T1 plateau cells ((32.6 +/- 4.3)%) is significantly less than T2 plateau ((47.5 +/- 5.6)%). MDC fluorescent intensity at T1 plateau (104.9 +/- 1 3.2) was significantly higher than intensity at T2 plateau (82.6 +/- 10.3). After cotreatment with insulin, the expression level of LC3-II, Beclin1 and PTEN in T2 plateau cells were significantly downregulated, but AKT, mTOR and PI3K expressions significantly upregulated compared with T1 plateau. Conclusions Insulin could enhance cisplatin-induced apoptosis in human esophageal squamous cell carcinoma EC9706 cells related to inhibition of autophagy. The activation of PI3K/Akt/mTOR signaling pathway induced by insulin resulted in the suppression of autophagy in EC9706 cells, which may be attributed to the anticancer effects of cisplatin.	[Yang Yang; Wen Fengbiao; Liu Donglei; Wu Kai; Zhao Song] Zhengzhou Univ, Dept Thorac Surg, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China; [Dang Lifeng] Zhengzhou Univ, Phys Examinat Ctr, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China; [Fan Yuxia] Zhengzhou Univ, Dept Thyroid Surg, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China; Zhengzhou Univ, Open Key Clin Med Expt Lab, Inst Henan Prov, Inst Mol Canc Surg, Zhengzhou 450052, Henan, Peoples R China; Key Thorac Tumour Expt Lab Zhengzhou, Zhengzhou 450052, Henan, Peoples R China		Zhao, S (corresponding author), Zhengzhou Univ, Dept Thorac Surg, Affiliated Hosp 1, 1 Jianshe East Rd, Zhengzhou 450052, Henan, Peoples R China.	zhaosong@zzu.edu.cn					Bao XX, 2012, CHINESE MED J-PEKING, V125, P3120, DOI 10.3760/cma.j.issn.0366-6999.2012.17.028; Barth S, 2010, J PATHOL, V221, P117, DOI 10.1002/path.2694; Chen Y, 2009, CELL DEATH DIFFER, V16, P1040, DOI 10.1038/cdd.2009.49; Choi KS, 2012, EXP MOL MED, V44, P109, DOI 10.3858/emm.2012.44.2.033; Gupta SC, 2011, ANN NY ACAD SCI, V1215, P150, DOI 10.1111/j.1749-6632.2010.05852.x; Han JF, 2011, CANCER LETT, V307, P200, DOI 10.1016/j.canlet.2011.04.004; Higgins CF, 2007, NATURE, V446, P749, DOI 10.1038/nature05630; Huerta S, 2006, AM J SURG, V191, P517, DOI 10.1016/j.amjsurg.2005.11.009; Kanzawa T, 2004, CELL DEATH DIFFER, V11, P448, DOI 10.1038/sj.cdd.4401359; Ko H, 2009, BIOSCI BIOTECH BIOCH, V73, P2183, DOI 10.1271/bbb.90250; Lee JS, 2012, METHODS, V56, P375, DOI 10.1016/j.ymeth.2011.11.006; Li J, 2010, EUR J CANCER, V46, P1900, DOI 10.1016/j.ejca.2010.02.021; Li J, 2009, ANN SURG ONCOL, V16, P761, DOI 10.1245/s10434-008-0260-0; Liu DL, 2011, MED ONCOL, V28, P105, DOI 10.1007/s12032-009-9397-3; Liu JL, 2013, BMC VET RES, V9, DOI 10.1186/1746-6148-9-75; Lozy F, 2012, SEMIN CELL DEV BIOL, V23, P395, DOI 10.1016/j.semcdb.2012.01.005; Miglietta A, 2004, CANCER LETT, V209, P139, DOI 10.1016/j.canlet.2003.12.023; Murtaza M, 2013, NATURE, V497, P108, DOI 10.1038/nature12065; Periyasamy Thandavan S, 2009, AM J PHYSIOL-RENAL, V297, pF244; Sinnberg T, 2009, J INVEST DERMATOL, V129, P1500, DOI 10.1038/jid.2008.379; Tomblyn MB, 2012, J THORAC ONCOL, V7, P906, DOI 10.1097/JTO.0b013e31824c7bed; van Hagen P, 2012, NEW ENGL J MED, V366, P2074, DOI 10.1056/NEJMoa1112088; Wang CF, 2013, CHINESE MED J-PEKING, V126, P1560, DOI 10.3760/cma.j.issn.0366-6999.20121225; White E, 2009, CLIN CANCER RES, V15, P5308, DOI 10.1158/1078-0432.CCR-07-5023; Zhou ST, 2012, CANCER LETT, V323, P115, DOI 10.1016/j.canlet.2012.02.017; Zou K, 2007, ACTA PHARMACOL SIN, V28, P721, DOI 10.1111/j.1745-7254.2007.00554.x	26	10	13	0	14	CHINESE MEDICAL ASSOC	BEIJING	42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA	0366-6999			CHINESE MED J-PEKING	Chin. Med. J.	JAN 20	2014	127	2					353	358		10.3760/cma.j.issn.0366-6999.20130996			6	Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	General & Internal Medicine	302LV	WOS:000330606900025	24438628				2022-04-25	
J	Kim, MJ; Kang, YJ; Sung, B; Jang, JY; Ahn, YR; Oh, HJ; Choi, H; Choi, I; Im, E; Moon, HR; Chung, HY; Kim, ND				Kim, Min Jeong; Kang, Young Jung; Sung, Bokyung; Jang, Jung Yoon; Ahn, Yu Ra; Oh, Hye Jin; Choi, Heejeong; Choi, Inkyu; Im, Eunok; Moon, Hyung Ryong; Chung, Hae Young; Kim, Nam Deuk			Novel SIRT Inhibitor, MHY2256, Induces Cell Cycle Arrest, Apoptosis, and Autophagic Cell Death in HCT116 Human Colorectal Cancer Cells	BIOMOLECULES & THERAPEUTICS			English	Article						SIRT inhibitor; MHY2256; Colorectal cancer cells; Cell cycle arrest; Apoptosis; Autophagy	DISCOVERY; D1	We examined the anticancer effects of a novel sirtuin inhibitor, MHY2256, on HCT116 human colorectal cancer cells to investigate its underlying molecular mechanisms. MHY2256 significantly suppressed the activity of sirtuin 1 and expression levels of sirtuin 1/2 and stimulated acetylation of forkhead box O1, which is a target protein of sirtuin 1. Treatment with MHY2256 inhibited the growth of the HCT116 (TP53 wild-type), HT-29 (TP53 mutant), and DLD-1 (TP53 mutant) human colorectal cancer cell lines. In addition, MHY2256 induced G0/G1 phase arrest of the cell cycle progression, which was accompanied by the reduction of cyclin D1 and cyclin E and the decrease of cyclin-dependent kinase 2, cyclin-dependent kinase 4, cyclin-dependent kinase 6, phosphorylated retinoblastoma protein, and E2F transcription factor 1. Apoptosis induction was shown by DNA fragmentation and increase in late apoptosis, which were detected using flow cytometric analysis. MHY2256 downregulated expression levels of procaspase-8, -9, and -3 and led to subsequent poly(ADP-ribose) polymerase cleavage. MHY2256-induced apoptosis was involved in the activation of caspase-8, -9, and -3 and was prevented by pretreatment with Z-VAD-FMK, a pan-caspase inhibitor. Furthermore, the autophagic effects of MHY2256 were observed as cytoplasmic vacuolation, green fluorescent protein-light-chain 3 punctate dots, accumulation of acidic vesicular organelles, and upregulated expression level of light-chain 3-II. Taken together, these results suggest that MHY2256 could be a potential novel sirtuin inhibitor for the chemoprevention or treatment of colorectal cancer or both.	[Kim, Min Jeong; Kang, Young Jung; Sung, Bokyung; Jang, Jung Yoon; Ahn, Yu Ra; Oh, Hye Jin; Choi, Heejeong; Choi, Inkyu; Im, Eunok; Moon, Hyung Ryong; Chung, Hae Young; Kim, Nam Deuk] Pusan Natl Univ, Coll Pharm, Div Pharm, Busan 46241, South Korea		Kim, ND (corresponding author), Pusan Natl Univ, Coll Pharm, Div Pharm, Busan 46241, South Korea.	nadkim@pusan.ac.kr	Sung, Bokyung/AAX-5697-2021	Kim, Nam Deuk/0000-0001-9033-9865	Pusan National UniversityPusan National University	This work was supported by a 2-Year Research Grant of Pusan National University.	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Ther.	NOV	2020	28	6					561	568		10.4062/biomolther.2020.153			8	Biochemistry & Molecular Biology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy	QC5YT	WOS:000614912400009	33073770	Green Published			2022-04-25	
J	Sun, XP; Veeraraghavan, VP; Surapaneni, KM; Hussain, S; Mathanmohun, M; Alharbi, SA; Aladresi, AAM; Chinnathambi, A				Sun, Xiaopeng; Veeraraghavan, Vishnu Priya; Surapaneni, Krishna Mohan; Hussain, Sardar; Mathanmohun, Maghimaa; Alharbi, Sulaiman Ali; Aladresi, Aref Ali Mohammed; Chinnathambi, Arunachalam			Eugenol-piperine loaded polyhydroxy butyrate/polyethylene glycol nanocomposite-induced apoptosis and cell death in nasopharyngeal cancer (C666-1) cells through the inhibition of the PI3K/AKT/mTOR signaling pathway	JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY			English	Article						apoptosis; C666-1 cells; eugenol; nasopharyngeal cancer; piperine; polyhydroxy butyrate	HERBS; NANOPARTICLES; NANOCARRIERS; ENHANCEMENT; ANTICANCER; AUTOPHAGY; DELIVERY; CARRIERS; DESIGN; FLUID	Nasopharyngeal cancer is a malignancy developing from the nasopharynx epithelium due to smoking and nitrosamine-containing foods. Nasopharyngeal cancer is highly endemic to Southeast Asia. Eugenol and piperine have shown many anticancer activities on numerous cancer types, like colon, lung, liver, and breast cancer. In this study, we amalgamated eugenol and piperine loaded with a polyhydroxy butyrate/polyethylene glycol nanocomposite (Eu-Pi/PHB-PEG-NC) for better anticancer results against nasopharyngeal cancer (C666-1) cells. In the current study, nasopharyngeal cancer cell lines C666-1 were utilized to appraise the cytotoxic potential of Eug-Pip-PEG-NC on cell propagation, programmed cell death, and relocation. Eu-Pi/PHB-PEG-NC inhibits cellular proliferation on C666-1 cells in a dose-dependent manner, and when compared with 20 mu g/ml, 15 mu g/ml of loaded mixture evidently restrained the passage aptitude of C666-1 cells, this was attended with a downregulated expression of mitochondrial membrane potential. Treatment with 15 mu g/ml Eu-Pi/PHB-PEG-NC suggestively amplified cell apoptosis in the C666-1 cells. Furthermore, its cleaved caspase-3, 8, and 9 and Bax gene expression was augmented and Bcl-2 gene expression was diminished after Eu-Pi/PHB-PEG-NC treatment. Additionally, our data established that the collective effect of Eu-Pi/PHB-PEG-NC loaded micelles inhibited the expansion of C666-1 cells augmented apoptosis connected with the intrusion of PI3K/Akt/mTOR signaling pathway.	[Sun, Xiaopeng] Xi An Jiao Tong Univ, Fac Med, Dept Surg, Xian, Peoples R China; [Sun, Xiaopeng] Xian Med Coll, Dept Otolaryngol, Affiliated Hosp 2, Xian, Peoples R China; [Veeraraghavan, Vishnu Priya] Saveetha Univ, Saveetha Inst Med & Tech Sci, Saveetha Dent Coll, Dept Biochem, Chennai, Tamil Nadu, India; [Surapaneni, Krishna Mohan] Panimalar Med Coll Hosp & Res Inst, Dept Biochem, Chennai, Tamil Nadu, India; [Surapaneni, Krishna Mohan] Panimalar Med Coll Hosp & Res Inst, Dept Clin Skills, Chennai, Tamil Nadu, India; [Surapaneni, Krishna Mohan] Panimalar Med Coll Hosp & Res Inst, Dept Simulat, Chennai, Tamil Nadu, India; [Hussain, Sardar] Govt Sci Coll, Dept Biotechnol, Chitradurga, Karnataka, India; [Mathanmohun, Maghimaa] Muthayammal Coll Arts & Sci, Dept MicroBiol, Rasipuram, Namakkal, Tamilnadu, India; [Alharbi, Sulaiman Ali; Aladresi, Aref Ali Mohammed; Chinnathambi, Arunachalam] King Saud Univ, Coll Sci, Dept Bot & Microbiol, Riyadh 11451, Saudi Arabia		Chinnathambi, A (corresponding author), King Saud Univ, Coll Sci, Dept Bot & Microbiol, Riyadh 11451, Saudi Arabia.	carunachalam@ksu.edu.sa	Krishna Mohan, Surapaneni/K-4865-2013; Mathanmohun, Maghimaa/AAY-6310-2020	Krishna Mohan, Surapaneni/0000-0002-5204-5708; Mathanmohun, Maghimaa/0000-0002-9043-435X	Deanship of Scientific Research at King Saud UniversityKing Saud University [RG-1435-081]	The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding of this study through the Research Group Number (RG-1435-081).	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J	Wang, J; Liang, D; Zhang, XP; He, CF; Cao, L; Zhang, SQ; Xiao, X; Li, SJ; Cao, YX				Wang, Jin; Liang, Dong; Zhang, Xue-Pei; He, Chen-Fei; Cao, Lei; Zhang, San-Qi; Xiao, Xue; Li, Shui-Jie; Cao, Yong-Xiao			Novel PI3K/Akt/mTOR signaling inhibitor, W922, prevents colorectal cancer growth via the regulation of autophagy	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						W922; PI3K; Akt; mTOR inhibitor; colorectal cancer; cell cycle arrest; autophagy	CELL-CYCLE; TARGETS; VS-5584; TUMOR	W922, a novel PI3K/Akt/mTOR pathway inhibitor, exhibits efficient anti-tumor effects on HCT116, MCF-7 and A549 human cancer cells compared with other synthesized compounds. The present study aimed to investigate its anti-tumor effects on colorectal cancer cells. A total, of seven different colorectal cell lines were selected to test the anti-proliferation profile of W922, and HCT116 was found to be the most sensitive cell line to the drug treatment. W922 inhibited HCT116 cell viability and cell proliferation in vitro in concentration- and time-dependent manners. Furthermore, W922 suppressed the tumor growth in a xenograft mouse model and exhibited low toxicity. The proteomic alterations in W922-treated HCT116 cells were found to be associated with cell cycle arrest, negative regulation of signal transduction and lysosome-related processes. W922 caused cell cycle arrest of HCT116 cells in G(0)-G(1) phase, but only triggered slight apoptosis. In addition, the PI3K/Akt/mTOR signaling proteins were dephosphorylated upon W922 treatment. It has been reported that inhibition of mTOR is relevant to autophagy, and the present results also indicated that W922 was involved in autophagy induction. An autophagy inhibitor, chloroquine, was used to co-treat HCT116 cells with W922, and it was identified that the cell cycle arrest was impaired. Moreover, co-treatment of W922 and chloroquine led to a significant population of apoptotic cells, thus providing a promising therapeutic strategy for colorectal cancer.	[Wang, Jin; Liang, Dong; Cao, Lei; Xiao, Xue; Cao, Yong-Xiao] Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pharmacol, 76 West Yanta Rd, Xian 710061, Shaanxi, Peoples R China; [Zhang, Xue-Pei] Chinese Acad Sci, Shanghai Inst Organ Chem, Ctr Excellence Mol Synth, State Key Lab Bioorgan & Nat Prod Chem, Shanghai 200032, Peoples R China; [He, Chen-Fei; Li, Shui-Jie] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, 9 Biomed Solnavagen, S-17165 Stockholm, Sweden; [Zhang, San-Qi] Xi An Jiao Tong Univ, Sch Pharm, Dept Pharmaceut Chem, Xian 710061, Shaanxi, Peoples R China		Cao, YX (corresponding author), Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pharmacol, 76 West Yanta Rd, Xian 710061, Shaanxi, Peoples R China.; Li, SJ (corresponding author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol, 9 Biomed Solnavagen, S-17165 Stockholm, Sweden.	shuijie.li@ki.se; yxy@mail.xjtu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81670001]; Natural Science Basic Research Project of Shaanxi Province [2018JQ8042]	This work was supported by the National Natural Science Foundation of China (grant no. 81670001) and Natural Science Basic Research Project of Shaanxi Province (grant no. 2018JQ8042).	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J. Oncol.	JAN	2021	58	1					70	82		10.3892/ijo.2020.5151			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	PE8RD	WOS:000598627700006	33367926	Green Published, hybrid			2022-04-25	
J	Choi, JH; Cho, YS; Ko, YH; Hong, SU; Park, JH; Lee, MA				Choi, Ji Hye; Cho, Young-Seok; Ko, Yoon Ho; Hong, Soon Uk; Park, Jin Hee; Lee, Myung Ah			Absence of Autophagy-Related Proteins Expression Is Associated with Poor Prognosis in Patients with Colorectal Adenocarcinoma	GASTROENTEROLOGY RESEARCH AND PRACTICE			English	Article							CANCER CELLS; BECLIN 1; TUMORIGENESIS; PATTERNS; LC3; INHIBITION; IMPACT	Background/Aim. Autophagy, a cellular degradation process, has paradoxical roles in tumorigenesis and the progression of human cancers. The aim of this study was to investigate the expression levels of autophagy-related proteins in colorectal cancer (CRC) and to evaluate their prognostic significance. Methods. This study is a retrospective review of immunohistochemical and clinicopathological data. All specimens evaluated were obtained from 263 patients with colorectal cancer who had undergone surgery between November 1996 and August 2007. The primary outcomes measured were the expression levels of three autophagy-related proteins (ATG5, BECN1/Beclin 1, and Microtubule-associated protein 1 light chain 3B (LC3B)) by immunohistochemistry and its association in clinicopathological parameters and patient survival. Results. The autophagy-related protein expression frequencies were 65.1% (151/232) for ATG5, 71.3% (174/244) for BECN1, and 74.7% (186/249) for LC3B for the 263 patients. Correlation between the expression of autophagy-related proteins was significant for all protein pairs. Multivariate analysis showed that negative LC3B expression and absence of autophagy-related proteins expression were independently associated with poor prognosis. Conclusion. Absence of autophagy-related proteins expression is associated with poor clinical outcome in CRC, suggesting that these proteins have potential uses as novel prognostic markers.	[Choi, Ji Hye; Park, Jin Hee] Catholic Univ Korea, Coll Med, Dept Biomed Sci, Seoul 137701, South Korea; [Cho, Young-Seok; Ko, Yoon Ho] Catholic Univ Korea, Coll Med, Uijeongbu St Marys Hosp, Dept Internal Med, Uijongbu 480717, South Korea; [Hong, Soon Uk] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul 138736, South Korea; [Lee, Myung Ah] Catholic Univ Korea, Coll Med, Seoul St Marys Hosp, Dept Internal Med, Seoul 137701, South Korea		Cho, YS (corresponding author), Catholic Univ Korea, Coll Med, Uijeongbu St Marys Hosp, Dept Internal Med, Uijongbu 480717, South Korea.	yscho@catholic.ac.kr; koyoonho@catholic.ac.kr			Institute of Clinical Medicine Research, Uijeongbu St. Mary's Hospital, The Catholic University of Korea; Basic Science Research Program through the National Research Foundation of Korea; Ministry of Education, Science and TechnologyMinistry of Education, Science and Technology, Republic of Korea [NRF-2010-0023295]	This study was supported by a grant of the Institute of Clinical Medicine Research, Uijeongbu St. Mary's Hospital, The Catholic University of Korea (Y.-S. Cho & Y. H. Ko) and a grant of Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (NRF-2010-0023295) (Y.-S. Cho).	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Res. Pract.		2014	2014								179586	10.1155/2014/179586			10	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	AD0AG	WOS:000332895600001	24723943	gold, Green Published, Green Submitted			2022-04-25	
J	Huang, C; He, CP; Ruan, P; Zhou, R				Huang, Chao; He, Chunping; Ruan, Peng; Zhou, Rui			TSPYL5 activates endoplasmic reticulum stress to inhibit cell proliferation, migration and invasion in colorectal cancer	ONCOLOGY REPORTS			English	Article						colorectal cancer; TSPYL5; endoplasmic reticulum stress; apoptosis; cell proliferation	ABERRANT PROMOTER METHYLATION; PROTECTIVE AUTOPHAGY; LUNG-CANCER; GROWTH; GENE; EXPRESSION; RESISTANCE; APOPTOSIS; AXIS	Testis-specific protein Y-encoded-like 5 (TSPYL5), a member of the nucleosome assembly protein (NAP) superfamily, functions as a tumor suppressor in ovarian and lung cancer, yet its clinical significance and molecular mechanism in colorectal cancer (CRC) remain unclear. TSPYL5 expression was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database. CRC cell lines HCT116 and HT29 were forced to overexpress TSPYL5 by transfection with pcDNA3.1-TSPYL5. Cell proliferation, apoptosis, migration, and invasion were examined by EdU proliferation assays, flow cytometry, and Transwell assays, respectively. Endoplasmic reticulum stress (ERS) was examined by transmission electron microscopy. Western blot analyses were performed to assess the expression of ERS-associated proteins. GEPIA database analysis showed that CRC patients had lower levels of TSPYL5 expression in their tumor tissues when compared with their para-carcinoma tissues. In vitro experiments indicated that TSPYL5 overexpression significantly suppressed cell proliferation, migration, and invasion, and induced apoptosis and ERS in HCT116 and HT29 cells. Furthermore, the levels of caspase-1, caspase-3, Bax, ATF4, and CHOP protein expression were upregulated after TSPYL5 was overexpressed. In conclusion, our data suggest that TSPYL5 can activate an ERS response that suppresses the proliferation, migration, and invasion of tumor cells. This mechanism may represent a promising therapeutic strategy for CRC.	[Huang, Chao; He, Chunping; Ruan, Peng; Zhou, Rui] Wuhan Univ, Renmin Hosp, Dept Gastroenterol, 99 Zhang Zhidong Rd, Wuhan 430060, Hubei, Peoples R China		Huang, C (corresponding author), Wuhan Univ, Renmin Hosp, Dept Gastroenterol, 99 Zhang Zhidong Rd, Wuhan 430060, Hubei, Peoples R China.	rmh_huangchao@126.com					Abe M, 2016, BMC CANCER, V16, DOI 10.1186/s12885-016-2371-5; Ansari SS, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0342-2; Ba-Omar TA, 2011, TISSUE CELL, V43, P29, DOI 10.1016/j.tice.2010.11.002; Bakhtou Hossein, 2019, Current Drug Discovery Technologies, V16, P184, DOI 10.2174/1570163815666180130101421; Epping MT, 2011, NAT CELL BIOL, V13, P102, DOI 10.1038/ncb2142; Han X, 2019, BIOMOL THER, V27, P41, DOI 10.4062/biomolther.2018.047; Huang C, 2018, DNA CELL BIOL, V37, P23, DOI 10.1089/dna.2017.3804; Jung Y, 2008, LAB INVEST, V88, P153, DOI 10.1038/labinvest.3700706; Khaket TP, 2018, CELL SIGNAL, V46, P92, DOI 10.1016/j.cellsig.2018.02.017; Kim EJ, 2010, BIOCHEM BIOPH RES CO, V392, P448, DOI 10.1016/j.bbrc.2010.01.045; Kim IY, 2019, BIOCHEM PHARMACOL, V162, P41, DOI 10.1016/j.bcp.2018.12.006; Kumar SR, 2017, BMC CANCER, V17, DOI 10.1186/s12885-017-3134-7; Lakshmanan I, 2017, CLIN CANCER RES, V23, P3906, DOI 10.1158/1078-0432.CCR-16-2530; Li ZC, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-018-1012-z; Liu JW, 2018, CELL SIGNAL, V48, P69, DOI 10.1016/j.cellsig.2018.05.001; Liu Y, 2017, APOPTOSIS, V22, P544, DOI 10.1007/s10495-016-1334-2; Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262; Lyu JH, 2015, J CELL BIOCHEM, V116, P260, DOI 10.1002/jcb.24964; Ma ZQ, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-08547-0; Mishra RR, 2018, CLIN CANCER RES, V24, P1987, DOI 10.1158/1078-0432.CCR-17-2776; Nakagawa T, 2000, NATURE, V403, P98, DOI 10.1038/47513; Qiu XP, 2016, DIGEST DIS SCI, V61, P149, DOI 10.1007/s10620-015-3878-3; Sepulveda AR, 2017, J CLIN ONCOL, V35, P1453, DOI 10.1200/JCO.2016.71.9807; Shao LP, 2017, DNA CELL BIOL, V36, P1108, DOI 10.1089/dna.2017.3904; Smeby J, 2018, ANN ONCOL, V29, P1227, DOI 10.1093/annonc/mdy085; Tauriello DVF, 2017, MOL ONCOL, V11, P97, DOI 10.1002/1878-0261.12018; Vogel T, 1998, CYTOGENET CELL GENET, V81, P265, DOI 10.1159/000015042; Wang Jian-Ping, 2011, Zhonghua Wei Chang Wai Ke Za Zhi, V14, P1; Wild C.P., 2014, ENCY TOXICOLOGY, V419, P1067, DOI DOI 10.1016/B978-0-12-386454-3.00402-4; Witek L, 2016, ADV MED SCI-POLAND, V61, P317, DOI 10.1016/j.advms.2016.04.001; Yang FMY, 2015, BIOMOLECULES, V5, P2538, DOI 10.3390/biom5042538	31	2	2	0	1	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1021-335X	1791-2431		ONCOL REP	Oncol. Rep.	AUG	2020	44	2					449	456		10.3892/or.2020.7639			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	NL1MT	WOS:000567188700004	32627024	hybrid, Green Published			2022-04-25	
J	Lee, AJX; Roylance, R; Sander, J; Gorman, P; Endesfelder, D; Kschischo, M; Jones, NP; East, P; Nicke, B; Spassieva, S; Obeid, LM; Birkbak, NJ; Szallasi, Z; McKnight, NC; Rowan, AJ; Speirs, V; Hanby, AM; Downward, J; Tooze, SA; Swanton, C				Lee, Alvin J. X.; Roylance, Rebecca; Sander, Jil; Gorman, Patricia; Endesfelder, David; Kschischo, Maik; Jones, Neil P.; East, Philip; Nicke, Barbara; Spassieva, Stefka; Obeid, Lina M.; Birkbak, Nicolai Juul; Szallasi, Zoltan; McKnight, Nicole C.; Rowan, Andrew J.; Speirs, Valerie; Hanby, Andrew M.; Downward, Julian; Tooze, Sharon A.; Swanton, Charles			CERT depletion predicts chemotherapy benefit and mediates cytotoxic and polyploid-specific cancer cell death through autophagy induction	JOURNAL OF PATHOLOGY			English	Article						CERT; autophagy; LAMP2; HER2; polyploidy; drug resistance	BREAST-CANCER; MITOTIC ARREST; CERAMIDE; SENSITIVITY; PACLITAXEL; GENES; ARRAY; SPHINGOLIPIDS; INTERFERENCE; METASTASIS	Chromosomal instability (CIN) has been implicated in multidrug resistance and the silencing of the ceramide transporter, CERT, promotes sensitization to diverse cytotoxics. An improved understanding of mechanisms governing multidrug sensitization might provide insight into pathways contributing to the death of CIN cancer cells. Using an integrative functional genomics approach, we find that CERT-specific multidrug sensitization is associated with enhanced autophagosomelysosome flux, resulting from the expression of LAMP2 following CERT silencing in colorectal and HER2+ breast cancer cell lines. Live cell microscopy analysis revealed that CERT depletion induces LAMP2-dependent death of polyploid cells following exit from mitosis in the presence of paclitaxel. We find that CERT is relatively over-expressed in HER2+ breast cancer and CERT protein expression acts as an independent prognostic variable and predictor of outcome in adjuvant chemotherapy-treated patients with primary breast cancer. These data suggest that the induction of LAMP2-dependent autophagic flux through CERT targeting may provide a rational approach to enhance multidrug sensitization and potentiate the death of polyploid cells following paclitaxel exposure to limit the acquisition of CIN and intra-tumour heterogeneity. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.	[Lee, Alvin J. X.; Sander, Jil; Endesfelder, David; East, Philip; Nicke, Barbara; McKnight, Nicole C.; Rowan, Andrew J.; Downward, Julian; Tooze, Sharon A.; Swanton, Charles] Canc Res UK London Res Inst, London WC2A 3LY, England; [Roylance, Rebecca; Gorman, Patricia] Queen Mary Univ London, Barts Canc Inst, London EC1M 6BQ, England; [Sander, Jil; Endesfelder, David; Kschischo, Maik] Univ Appl Sci Koblenz, D-53424 Remagen, Germany; [Jones, Neil P.] UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England; [Spassieva, Stefka; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA; [Obeid, Lina M.] Ralph H Johnson Vet Affairs Hosp, Div Gen Internal Med, Charleston, SC 29401 USA; [Birkbak, Nicolai Juul; Szallasi, Zoltan] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark; [Birkbak, Nicolai Juul] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA; [Szallasi, Zoltan] Harvard Univ, Sch Med, Childrens Hosp, Harvard MIT Div Hlth Sci & Technol,Informat Progr, Boston, MA 02115 USA; [Speirs, Valerie; Hanby, Andrew M.] Univ Leeds, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England; [Swanton, Charles] UCL Canc Inst, London WC1E 6BT, England; [Swanton, Charles] Macmillan Canc Ctr, London WC1E 6BT, England		Swanton, C (corresponding author), Canc Res UK London Res Inst, 44 Lincolns Inn Fields, London WC2A 3LY, England.	charles.swanton@cancer.org.uk	Speirs, Valerie/ABE-7377-2021; Lee, Alvin Jun Xing/A-1047-2017; Downward, Julian/A-3251-2012	Speirs, Valerie/0000-0002-0602-4666; Lee, Alvin Jun Xing/0000-0002-7427-9142; obeid, lina/0000-0002-0734-0847; Tooze, Sharon/0000-0002-2182-3116; Swanton, Charles/0000-0002-4299-3018; Howell, Michael/0000-0003-0912-0079; McKnight, Nicole/0000-0003-4269-3960; Downward, Julian/0000-0002-2331-4729; East, Philip/0000-0001-5801-5713; Szallasi, Zoltan/0000-0001-5395-7509; Birkbak, Nicolai/0000-0003-1613-9587	National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NCI SPORE P50 CA 89393, R21LM008823-01A1]; Danish Council for Independent Research/Medical Sciences (FSS)Det Frie Forskningsrad (DFF)Danish Medical Research Council; Breast Cancer Research Foundation (BCRF); Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission; CR-UKCancer Research UK; Cancer Research UKCancer Research UK [15680] Funding Source: researchfish; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [G0701935] Funding Source: researchfish; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P50CA089393, P01CA097132] Funding Source: NIH RePORTER; NATIONAL CENTER FOR RESEARCH RESOURCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [P20RR017677] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGINGUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01AG016583] Funding Source: NIH RePORTER; NATIONAL LIBRARY OF MEDICINEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Library of Medicine (NLM) [R21LM008823] Funding Source: NIH RePORTER; Veterans AffairsUS Department of Veterans Affairs [I01BX000156] Funding Source: NIH RePORTER; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [G0701935] Funding Source: UKRI	We thank the following: Sarah McClelland, Jasmin Zohren and Rebecca Burrell for help with manuscript preparation; Hannah Armer and Lucy Collinson from the EM facility at Cancer Research UK (CR-UK) LRI and Niamh Murphy for help with the breast cancer TMA cohort. CS is funded by the Medical Research Council and CR-UK. AL, NM, AR, JD and ST are funded by CR-UK. ZS is funded by the National Institute of Health (Grant Nos NCI SPORE P50 CA 89393 and R21LM008823-01A1), the Danish Council for Independent Research/Medical Sciences (FSS) and the Breast Cancer Research Foundation (BCRF).	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Pathol.	FEB	2012	226	3					482	494		10.1002/path.2998			13	Oncology; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pathology	877DY	WOS:000299158400011	21953249	Green Published			2022-04-25	
J	Wang, ZZ; Jin, JJ				Wang, Zhaozhi; Jin, Jianjun			LncRNA SLCO4A1-AS1 promotes colorectal cancer cell proliferation by enhancing autophagy via miR-508-3p/PARD3 axis	AGING-US			English	Article						colorectal cancer (CRC); SLCO4A1-AS1; PARD3; miR-508-3p; autophagy	LONG NONCODING RNAS; DOWN-REGULATION; STATISTICS; CARCINOMA; INVASION	Aberrant expressions of various long non-coding RNAs (lncRNAs) have been involved in the progression and pathogenesis of various carcinomas. However, the expression and biological function of SLCO4A1-AS1 in colorectal cancer (CRC) remain poorly understood. Gain-and loss-of-function assays were applied to determine the roles of SLCO4A1-AS1 in autophagy and CRC progression. qRT-PCR and in situ hybridization (ISH) results showed that SLCO4A1-AS1 was positively associated with PARD3 expression in CRC tissues. In vitro and in vivo studies revealed that SLCO4A1-AS1 knockdown repressed cytoprotective autophagy as assayed by transmission electron microscopy (TEM), and inhibited cell proliferation by directly targeting partition-defective 3 (PARD3). Mechanistically, SLCO4A1-AS1 acted as a sponge of miR-508-3p, leading to upregulation of PARD3 and promotion of CRC cell proliferation. The current study demonstrates that the SLCO4A1-AS1/miR-5083p/PARD3/autophagy pathway play a critical role in CRC cell proliferation, and might provide novel targets for developing therapeutic strategies for CRC.	[Wang, Zhaozhi; Jin, Jianjun] Henan Univ Sci & Technol, Affiliated Hosp 1, Dept Gastrointestinal Med, Luoyang 471003, Henan, Peoples R China; [Wang, Zhaozhi; Jin, Jianjun] Henan Univ Sci & Technol, Coll Clin Med, Luoyang 471003, Henan, Peoples R China		Wang, ZZ (corresponding author), Henan Univ Sci & Technol, Affiliated Hosp 1, Dept Gastrointestinal Med, Luoyang 471003, Henan, Peoples R China.; Wang, ZZ (corresponding author), Henan Univ Sci & Technol, Coll Clin Med, Luoyang 471003, Henan, Peoples R China.	wangzhaozhiroy@163.com					Choi EJ, 2018, PATHOL ONCOL RES, V24, P827, DOI 10.1007/s12253-017-0297-0; Gonzalez V, 2010, BIOCHEMISTRY-US, V49, P9706, DOI 10.1021/bi100509s; Gu P, 2017, MOL THER, V25, P1959, DOI 10.1016/j.ymthe.2017.04.016; Han Y, 2014, PATHOLOGY, V46, P396, DOI 10.1097/PAT.0000000000000125; Huang T, 2018, MED SCI MONITOR, V24, P7340, DOI 10.12659/MSM.910054; Kondo Y, 2017, CANCER SCI, V108, P1927, DOI 10.1111/cas.13342; Li MH, 2018, ONCOTARGETS THER, V11, P6295, DOI 10.2147/OTT.S168807; Li S, 2018, J CELL PHYSIOL, V233, P6679, DOI 10.1002/jcp.26325; Liu HB, 2019, J CELL PHYSIOL, V234, P13843, DOI 10.1002/jcp.28064; Liu XH, 2014, MOL CANCER, V13, DOI 10.1186/1476-4598-13-92; Luo J, 2016, ONCOL REP, V35, P2035, DOI 10.3892/or.2016.4606; McShane LM, 2005, BRIT J CANCER, V93, P387, DOI 10.1038/sj.bjc.6602678; Migliore L, 2011, J BIOMED BIOTECHNOL, DOI 10.1155/2011/792362; Miller KD, 2016, CA-CANCER J CLIN, V66, P271, DOI 10.3322/caac.21349; Siegel RL, 2019, CA-CANCER J CLIN, V69, P7, DOI 10.3322/caac.21551; Siegel RL, 2017, CA-CANCER J CLIN, V67, P177, DOI 10.3322/caac.21395; von Elm E, 2007, LANCET, V370, P1453, DOI [10.2471/BLT.07.045120, 10.1371/journal.pmed.0040296, 10.1016/j.jclinepi.2007.11.008]; Wan WJ, 2019, CELL DEATH DIS, V10, DOI 10.1038/s41419-019-1440-5; Wang F, 2018, BIOCHEM BIOPH RES CO, V504, P171, DOI 10.1016/j.bbrc.2018.08.150; Wang QM, 2019, CANCER CELL INT, V19, DOI 10.1186/s12935-019-0760-y; Wang S, 2017, CELL DEATH DIS, V8, DOI 10.1038/cddis.2017.485; Yang YX, 2019, CELL DEATH DIS, V10, DOI 10.1038/s41419-018-1280-8; Yang ZY, 2017, CANCER BIOMARK, V18, P95, DOI 10.3233/CBM-161715; Zhang KC, 2017, THERANOSTICS, V7, P213, DOI 10.7150/thno.16044; Zhou HY, 2016, CANCER BIOMARK, V17, P1, DOI 10.3233/CBM-160613; Zhou QY, 2017, CELL SIGNAL, V38, P49, DOI 10.1016/j.cellsig.2017.06.016	26	22	23	1	3	IMPACT JOURNALS LLC	ORCHARD PARK	6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA	1945-4589			AGING-US	Aging-US	JUL 31	2019	11	14					4876	4889		10.18632/aging.102081			14	Cell Biology; Geriatrics & Gerontology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Geriatrics & Gerontology	IO1KN	WOS:000479140500010	31308265	Green Published, gold			2022-04-25	
J	Germani, A; Matrone, A; Grossi, V; Peserico, A; Sanese, P; Liuzzi, M; Palermo, R; Murzilli, S; Campese, AF; Ingravallo, G; Canettieri, G; Tezil, T; Simone, C				Germani, Aldo; Matrone, Antonio; Grossi, Valentina; Peserico, Alessia; Sanese, Paola; Liuzzi, Micaela; Palermo, Rocco; Murzilli, Stefania; Campese, Antonio Francesco; Ingravallo, Giuseppe; Canettieri, Gianluca; Tezil, Tugsan; Simone, Cristiano			Targeted therapy against chemoresistant colorectal cancers: Inhibition of p38 alpha modulates the effect of cisplatin in vitro and in vivo through the tumor suppressor FoxO3A	CANCER LETTERS			English	Article						Dual therapy; p38 MAPK; Chemoresistance; Colorectal cancer; Cell death	ACTIVATED PROTEIN-KINASES; P38 MAPK; OVARIAN-CANCER; AMPK-FOXO3A AXIS; CELL-DEATH; RESISTANCE; CARCINOMA; AUTOPHAGY; COPPER; ERK	Chemoresistance is a major obstacle to effective therapy against colorectal cancer (CRC) and may lead to deadly consequences. The metabolism of CRC cells depends highly on the p38 MAPK pathway, whose involvement in maintaining a chemoresistant behavior is currently being investigated. Our previous studies revealed that p38 alpha is the main p38 isoform in CRC cells. Here we show that p38 alpha pharmacological inhibition combined with cisplatin administration decreases colony formation and viability of cancer cells and strongly increases Bax-dependent apoptotic cell death by activating the tumor suppressor protein FoxO3A. Our results indicate that FoxO3A activation up-regulates transcription of its target genes (p21, PTEN, Bim and GADD45), which forces both chemosensitive and chemoresistant CRC cells to undergo apoptosis. Additionally, we found that FoxO3A is required for apoptotic cell death induction, as confirmed by RNA interference experiments. In animal models xenografted with chemoresistant HT29 cells, we further confirmed that the p38-targeted dual therapy strategy produced an increase in apoptosis in cancer tissue leading to tumor regression. Our study uncovers a major role for the p38FoxO3A axis in chemoresistance, thereby suggesting a new therapeutic approach for CRC treatment; moreover, our results indicate that Bax status may be used as a predictive biomarker. (C) 2013 Elsevier Ireland Ltd. All rights reserved.	[Germani, Aldo; Matrone, Antonio; Peserico, Alessia; Sanese, Paola; Tezil, Tugsan; Simone, Cristiano] Consorzio Mario Negri Sud, DTP, Lab Signal Dependent Transcript, I-66030 Santa Maria Imbaro, Ch, Italy; [Grossi, Valentina] IRCCS S de Bellis, Canc Genet Lab, I-70013 Castellana Grotte, Italy; [Liuzzi, Micaela; Ingravallo, Giuseppe] Univ Bari, DETO, Div Anat Pathol, I-70124 Bari, Italy; [Palermo, Rocco; Campese, Antonio Francesco; Canettieri, Gianluca] Ist Italiano Tecnol, Ctr Life Nano Sci Sapienza, Rome, Italy; [Murzilli, Stefania] Consorzio Mario Negri Sud, DTP, Anim Care Facil, I-66030 Santa Maria Imbaro, Ch, Italy; [Simone, Cristiano] Univ Bari, DIMO, Div Med Genet, I-70124 Bari, Italy		Tezil, T (corresponding author), Consorzio Mario Negri Sud, DTP, Lab Signal Dependent Transcript, Via Nazl 8-A, I-66030 Santa Maria Imbaro, Ch, Italy.	teziltugsan@sabanciuniv.edu; cristiano.simone@uniba.it	Tezil, Tugsan/A-3909-2013; GROSSI, Valentina/O-6546-2019; Ingravallo, Giuseppe/Q-1477-2016; tezil, tugsan/P-4053-2019; Grossi, Valentina/K-9821-2016; Campese, Antonio/A-9783-2015; INGRAVALLO, Giuseppe/N-2466-2019; Palermo, Rocco/I-5140-2016; Sanese, Paola/AAC-1991-2019; Simone, Cristiano/K-3452-2018	Tezil, Tugsan/0000-0003-0796-3718; GROSSI, Valentina/0000-0003-3843-1618; Ingravallo, Giuseppe/0000-0002-4792-3545; Grossi, Valentina/0000-0003-3843-1618; INGRAVALLO, Giuseppe/0000-0002-4792-3545; Palermo, Rocco/0000-0003-0134-9370; Simone, Cristiano/0000-0002-2628-7658; Sanese, Paola/0000-0001-8872-7498; CANETTIERI, Gianluca/0000-0001-6694-2613; Peserico, Alessia/0000-0003-2025-2419	Italian Foundation for Cancer Research (FIRC) fellowshipsFondazione AIRC per la ricerca sul cancro; Italian Association for Cancer Research (AIRC)Fondazione AIRC per la ricerca sul cancro [IG10177]; Italian Fund for Basic Research (FIRB)	We thank Dr Francesco Paolo Joni for his helpful discussion during the preparation of the manuscript and editorial assistance. T.T. and A.P. are supported by Italian Foundation for Cancer Research (FIRC) fellowships. This study was partially supported by an 'Investigator Grant 2010' (IG10177) (to C.S.) from the Italian Association for Cancer Research (AIRC) and the Italian Fund for Basic Research (FIRB).	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J	Xia, F; Liu, PQ; Li, M				Xia, Fan; Liu, Peiqing; Li, Min			The regulatory factors and pathological roles of autophagy-related protein 4 in diverse diseases: Recent research advances	MEDICINAL RESEARCH REVIEWS			English	Review						ATG4; autophagy; disease; inhibitor; regulatory factor	HEPATOCELLULAR-CARCINOMA; UP-REGULATION; COLORECTAL-CANCER; DOWN-REGULATION; LUNG-CANCER; ISCHEMIA/REPERFUSION INJURY; ATG8-PE DECONJUGATION; SUPPRESSES AUTOPHAGY; ATTENUATES AUTOPHAGY; CONJUGATION SYSTEMS	Macroautophagy (autophagy) is an evolutionarily conserved and dynamic degradation/recycling pathway in which portions of the cytoplasm, such as dysfunctional proteins and surplus organelles, are engulfed by double-membrane bound vesicles through a lysosome-dependent process. As the only proteolytic enzyme of the core mammalian autophagy proteins, autophagy-related protein 4 (ATG4) primes newly synthesized pro-light chain 3 (LC3) to form LC3-I that attaches to phosphatidylethanolamine and delipidates LC3-PE to LC3-I for recycling. Besides autophagy, ATG4 has been shown to be involved in regulating various biological and pathological processes. The roles of ATG4 in cancer therapy, a methodology for ATG4 activity detection, and the discovery of chemical modulators have been well-reviewed. However, a comprehensive summary on how ATG4 is regulated by multiple factors and, thereby, how ATG4 influences autophagy or other pathways remains lacking. In this paper, we summarize multiple processes and molecules that regulate the activity of ATG4, such as micro-RNAs, posttranslational modifications, and small molecules. Additionally, we focus on the relationship between ATG4 and diverse diseases, including cancer, neurodegeneration, microbial infection, and other diseases. It provides insight regarding potential ATG4-targeted therapeutic opportunities, which could be beneficial for future studies and human health.	[Xia, Fan; Liu, Peiqing; Li, Min] Sun Yat Sen Univ, Natl & Local United Engn Lab Druggabil & New Drug, Guangdong Prov Key Lab Chiral Mol & Drug Discover, Sch Pharmaceut Sci,Dept Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China		Liu, PQ; Li, M (corresponding author), Sun Yat Sen Univ, Natl & Local United Engn Lab Druggabil & New Drug, Guangdong Prov Key Lab Chiral Mol & Drug Discover, Sch Pharmaceut Sci,Dept Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China.	liupq@mail.sysu.edu.cn; limin65@mail.sysu.edu.cn		li, min/0000-0002-5657-8675	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31970699, 31671437]; Guangdong Basic and Applied Basic Research Foundation [2019A1515011030]; Guangdong Provincial Key Laboratory of Construction Foundation [2019B030301005]; Key-Area Research and Development Program of Guangdong Province [2020B1111110003]; National Major Special Projects for the Creation and Manufacture of New Drugs [2019ZX09301104]	This study was supported by the National Natural Science Foundation of China (31970699 and 31671437), the Guangdong Basic and Applied Basic Research Foundation (2019A1515011030), the Guangdong Provincial Key Laboratory of Construction Foundation (2019B030301005), the Key-Area Research and Development Program of Guangdong Province (2020B1111110003), and the National Major Special Projects for the Creation and Manufacture of New Drugs (2019ZX09301104).	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Res. Rev.	MAY	2021	41	3					1644	1675		10.1002/med.21772		DEC 2020	32	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	RM3PS	WOS:000598258200001	33314291				2022-04-25	
J	Qiu, GL; Li, XQ; Che, XM; Wei, C; He, SC; Lu, J; Jia, ZL; Pang, K; Fan, L				Qiu, Guanglin; Li, Xuqi; Che, Xiangming; Wei, Chao; He, Shicai; Lu, Jing; Jia, Zongliang; Pang, Ke; Fan, Lin			SIRT1 is a regulator of autophagy: Implications in gastric cancer progression and treatment	FEBS LETTERS			English	Review						Gastric cancer; Silent mating type information regulation 1; Autophagy; Tumor suppressor; Tumor promoter	HISTONE DEACETYLASE EXPRESSION; RAPAMYCIN-INDUCED AUTOPHAGY; CELL CARCINOMA PATIENTS; HELICOBACTER-PYLORI; COLORECTAL-CANCER; POOR-PROGNOSIS; CLINICOPATHOLOGICAL SIGNIFICANCE; VACUOLATING CYTOTOXIN; UP-REGULATION; DNA-DAMAGE	Silent mating type information regulation 1 (SIRT1) is implicated in tumorigenesis through its effect on autophagy. In gastric cancer (GC), SIRT1 is a marker for prognosis and is involved in cell invasion, proliferation, epithelial-mesenchymal transition (EMT) and drug resistance. Autophagy can function as a cell-survival mechanism or lead to cell death during the genesis and treatment of GC. This functionality is determined by factors including the stage of the tumor, cellular context and stress levels. Interestingly, SIRT1 can regulate autophagy through the deacetylation of autophagy-related genes (ATGs) and mediators of autophagy. Taken together, these findings support the need for continued research efforts to understand the mechanisms mediating the development of gastric cancer and unveil new strategies to eradicate this disease. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.	[Qiu, Guanglin; Li, Xuqi; Che, Xiangming; He, Shicai; Lu, Jing; Jia, Zongliang; Fan, Lin] Xi An Jiao Tong Univ, Dept Gen Surg, Affiliated Hosp 1, Coll Med, Xian 710061, Shaanxi Provinc, Peoples R China; [Wei, Chao] Xian Hlth Sch, Xian 710054, Shaanxi Provinc, Peoples R China; [Pang, Ke] Shaanxi Friendship Hosp, Xian 710068, Shaanxi Provinc, Peoples R China		Fan, L (corresponding author), Xi An Jiao Tong Univ, Dept Gen Surg, Affiliated Hosp 1, Coll Med, 277 Yanta West Rd, Xian 710061, Shaanxi Provinc, Peoples R China.	linnet@mail.xjtu.edu.cn	Li, Xuqi/B-3090-2014	Li, Xuqi/0000-0002-2497-020X	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81270150]; International Cooperation Project of Science and Technology Research of Shaanxi Province [2012KW-41]	This study was supported by grants from the National Natural Science Foundation of China (No. 81270150) and the International Cooperation Project of Science and Technology Research of Shaanxi Province (No. 2012KW-41).	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JUL 22	2015	589	16					2034	2042		10.1016/j.febslet.2015.05.042			9	Biochemistry & Molecular Biology; Biophysics; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics; Cell Biology	CN9XT	WOS:000358805100002	26049033	Bronze			2022-04-25	
J	Bortolami, M; Comparato, A; Benna, C; Errico, A; Maretto, I; Pucciarelli, S; Cillo, U; Farinati, F				Bortolami, Marina; Comparato, Alessandra; Benna, Clara; Errico, Andrea; Maretto, Isacco; Pucciarelli, Salvatore; Cillo, Umberto; Farinati, Fabio			Gene and protein expression of mTOR and LC3 in hepatocellular carcinoma, colorectal liver metastasis and "normal" liver tissues	PLOS ONE			English	Article							HEPATITIS-B-VIRUS; MAMMALIAN TARGET; AUTOPHAGY; CANCER; PHOSPHORYLATION; INFLAMMATION; RESISTANCE; MICRORNAS; PATHWAY; MICE	The physiological role of autophagy in the progression of liver diseases is still debated. To understand the clinical relevance of autophagy in primary e secondary hepatic tumors, we analyzed the expression of mTOR (mammalian target of rapamycin), a key regulator of autophagy; Raptor (regulatory-associated protein of mTOR); ULK1 (Unc-51 like kinase 1) determinant in the autophagy initiation; LC3 (microtubule-associated protein 1A/1B-light chain 3), a specific marker of autophagosomes; and p62, a selective autophagy receptor. Samples from subjects with chronic hepatitis (n.58), cirrhosis (n.12), hepatocellular carcinoma (HCC, n.56), metastases (n.48) from colorectal cancer and hyperplasia or gallbladder stones (n.7), the latter considered as controls, were examined. Gene expression analysis was carried out in n.213 tissues by absolute q-PCR, while protein expression by Western Blot in n.191 lysates, including tumoral, surrounding tumoral and normal tissues. Nonparametric statistical tests were used for comparing expression levels in the above-mentioned groups. Subgroup analysis was performed considering viral infection and chemotherapy treatment. The mTOR transcriptional level was significantly lower in metastases compared to HCC (P = 0.0001). p-mTOR(Ser2448) and LC3II/LC3I protein levels were significantly higher in metastases compared to HCC (P = 0.008 and P<0.0001, respectively). ULK(Ser757) levels were significantly higher in HCC compared to metastases (P = 0.0002) while the HCV- and HBV- related HCC showed the highest p62 levels. Chemotherapy induced a down-regulation of the p-mTOR(Ser2448) in metastases and in non-tumor surrounding tissues in treated patients compared to untreated (P = 0.001 and P = 0.005, respectively). Conclusions: the different expression of proteins considered, owning their interaction and diverse tissue microenvironment, indicate an impairment of the autophagy flux in primary liver tumors that is critical for the promotion of tumorigenesis process and a coexistence of autophagy inhibition and activation mechanisms in secondary liver tumors. Differences in mTOR and LC3 transcripts emerged in tumor-free tissues, therefore particular attention should be considered in selecting the control group.	[Bortolami, Marina; Comparato, Alessandra; Errico, Andrea; Farinati, Fabio] Univ Padua, Dept Surg Oncol & Gastroenterol, DISCOG, Sch Med,Gastroenterol Unit, Padua, Italy; [Benna, Clara; Maretto, Isacco; Pucciarelli, Salvatore; Cillo, Umberto] Univ Padua, Dept Surg Oncol & Gastroenterol, DISCOG, Sch Med,Surg Unit, Padua, Italy		Bortolami, M (corresponding author), Univ Padua, Dept Surg Oncol & Gastroenterol, DISCOG, Sch Med,Gastroenterol Unit, Padua, Italy.	marina.bortolami@unipd.it	benna, clara/K-1083-2018; PUCCIARELLI, SALVATORE/J-5050-2018	FARINATI, FABIO/0000-0002-2944-1374; PUCCIARELLI, SALVATORE/0000-0001-5289-9925	University of Padova [BIRD175781]	MB: 2017-prot. BIRD175781 University of Padova The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Liu, JT; Fan, LL; Wang, H; Sun, GP				Liu, Jiatao; Fan, Lulu; Wang, Hua; Sun, Guoping			Autophagy, a double-edged sword in anti-angiogenesis therapy	MEDICAL ONCOLOGY			English	Review						Autophagy; Anti-angiogenesis; Hypoxia	HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; METASTATIC COLORECTAL-CANCER; PLATINUM-BASED CHEMOTHERAPY; HEPATOCELLULAR-CARCINOMA; CELL-DEATH; ANTIANGIOGENIC THERAPY; DRUG-RESISTANCE; LUNG-CANCER; CISPLATIN RESISTANCE; TUMOR ANGIOGENESIS	Autophagy is a highly conservative cell behavior to keep the intracellular homeostasis and is frequently activated when cells encounter disgusting conditions, such as nutrition or growth factor deprive, hypoxia and cytotoxic agents. However, the precise role of autophagy under various conditions may be opposite, differ from protect cells survival to promote cells death, and the mechanism of this conditional-dependent role is still unclear. Anti-angiogenesis agents, such as bevacizumab, sorafenib and sunitinib, could reduce tumor microvascular density and increase tumor hypoxia, thus up-regulating autophagy activation of tumor cells, but the function of autophagy induced by anti-angiogenesis agents is still divergent and is considered to play a cytoprotective role in most cases. In this review, we mainly discuss the relationship between anti-angiogenesis therapy-induced hypoxia and autophagy, and pay special attention on the exact role of anti-angiogenesis agents induced autophagy in the process of anti-angiogenesis treatment.	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J	Gil, J; Karpinski, P; Sasiadek, MM				Gil, Justyna; Karpinski, Pawel; Sasiadek, Maria M.			Transcriptomic Profiling for the Autophagy Pathway in Colorectal Cancer	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						autophagy; gene expression; colorectal cancer	CONSENSUS MOLECULAR SUBTYPES; EXPRESSION; TUMORIGENESIS; MUTATIONS; UNDERLIE; PROTEINS	The role of autophagy in colorectal cancer (CRC) pathogenesis appears to be crucial. Autophagy acts both as a tumor suppressor, by removing redundant cellular material, and a tumor-promoting factor, by providing access to components necessary for growth, metabolism, and proliferation. To date, little is known about the expression of genes that play a basal role in the autophagy in CRC. In this study, we aimed to compare the expression levels of 46 genes involved in the autophagy pathway between tumor-adjacent and tumor tissue, employing large RNA sequencing (RNA-seq) and microarray datasets. Additionally, we verified our results using data on 38 CRC cell lines. Gene set enrichment analysis revealed a significant deregulation of autophagy-related gene sets in CRC. The unsupervised clustering of tumors using the mRNA levels of autophagy-related genes revealed the existence of two major clusters: microsatellite instability (MSI)-enriched and -depleted. In cluster 1 (MSI-depleted), ATG9B and LAMP1 genes were the most prominently expressed, whereas cluster 2 (MSI-enriched) was characterized by DRAM1 upregulation. CRC cell lines were also clustered according to MSI-enriched/-depleted subgroups. The moderate deregulation of autophagy-related genes in cancer tissue, as compared to adjacent tissue, suggests a prominent field cancerization or early disruption of autophagy. Genes differentiating these clusters are promising candidates for CRC targeting therapy worthy of further investigation.	[Gil, Justyna; Karpinski, Pawel; Sasiadek, Maria M.] Wroclaw Med Univ, Dept Genet, Marcinkowskiego 1, PL-50368 Wroclaw, Poland; [Karpinski, Pawel] Polish Acad Sci, Inst Immunol & Expt Therapy, Lab Genom & Bioinformat, PL-53114 Wroclaw, Poland		Gil, J (corresponding author), Wroclaw Med Univ, Dept Genet, Marcinkowskiego 1, PL-50368 Wroclaw, Poland.		Karpinski, Pawel/U-3313-2018	Karpinski, Pawel/0000-0003-3885-694X; Gil, Justyna/0000-0003-0991-7686; Sasiadek, Maria/0000-0002-7599-7074			Alessandrini F, 2017, SEMIN ONCOL, V44, P239, DOI 10.1053/j.seminoncol.2017.10.013; Alhamdoosh M, 2017, BIOINFORMATICS, V33, P414, DOI 10.1093/bioinformatics/btw623; Amaravadi R, 2016, GENE DEV, V30, P1913, DOI 10.1101/gad.287524.116; Aran D, 2017, NAT COMMUN, V8, DOI 10.1038/s41467-017-01027-z; Arnold M, 2017, GUT, V66, P683, DOI 10.1136/gutjnl-2015-310912; Bendell JC, 2012, J CLIN ONCOL, V30, DOI 10.1200/jco.2012.30.18_suppl.lba3501; Crighton D, 2006, CELL, V126, P121, DOI 10.1016/j.cell.2006.05.034; Dai MH, 2005, NUCLEIC ACIDS RES, V33, DOI 10.1093/nar/gni179; Devenport SN, 2019, CELLS-BASEL, V8, DOI 10.3390/cells8111349; Eide PW, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-16747-x; Filzmoser P, 2013, INFORM SCIENCES, V245, P4, DOI 10.1016/j.ins.2012.10.017; Folkerts H, 2019, MED RES REV, V39, P517, DOI 10.1002/med.21531; Freeman T.J., 2012, GASTROENTEROLOGY, V142, P562; Furuta K, 2001, AM J PATHOL, V159, P449, DOI 10.1016/S0002-9440(10)61716-6; Galluzzi L, 2015, EMBO J, V34, P856, DOI 10.15252/embj.201490784; Gandhi J, 2017, BRIT J SURG, V104, P1063, DOI 10.1002/bjs.10518; Gewirtz DA, 2014, CANCER RES, V74, P647, DOI 10.1158/0008-5472.CAN-13-2966; Gil J, 2016, BIOMARK MED, V10, P1081, DOI 10.2217/bmm-2016-0083; Gil J, 2010, WSPOLCZESNA ONKOL, V14, P211, DOI 10.5114/wo.2010.14132; Gilcrease GW, 2019, INVEST NEW DRUG, V37, P482, DOI 10.1007/s10637-018-0645-2; Guan JJ, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2014.546; Guinney J, 2015, NAT MED, V21, P1350, DOI 10.1038/nm.3967; Hashim D, 2016, ANN ONCOL, V27, P926, DOI 10.1093/annonc/mdw027; Hoadley KA, 2014, CELL, V158, P929, DOI 10.1016/j.cell.2014.06.049; Huang Z, 2019, DOSE-RESPONSE, V17, DOI 10.1177/1559325819894179; Iorio F, 2016, CELL, V166, P740, DOI 10.1016/j.cell.2016.06.017; Johnson WE, 2007, BIOSTATISTICS, V8, P118, DOI 10.1093/biostatistics/kxj037; Jorissen RN, 2009, CLIN CANCER RES, V15, P7642, DOI 10.1158/1078-0432.CCR-09-1431; Jorissen RN, 2008, CLIN CANCER RES, V14, P8061, DOI 10.1158/1078-0432.CCR-08-1431; Kang MR, 2009, J PATHOL, V217, P702, DOI 10.1002/path.2509; Keller CW, 2018, CURR OPIN IMMUNOL, V52, P68, DOI 10.1016/j.coi.2018.04.014; Kemper K, 2012, CLIN CANCER RES, V18, P3132, DOI 10.1158/1078-0432.CCR-11-3066; Koustas E, 2019, CANCERS, V11, DOI 10.3390/cancers11040533; LaPointe LC, 2008, PHYSIOL GENOMICS, V33, P50, DOI 10.1152/physiolgenomics.00185.2006; Li ST, 2013, FUTURE ONCOL, V9, P727, DOI [10.2217/FON.13.25, 10.2217/fon.13.25]; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Linnekamp JF, 2018, CELL DEATH DIFFER, V25, P616, DOI 10.1038/s41418-017-0011-5; Maes H, 2013, TRENDS MOL MED, V19, P428, DOI 10.1016/j.molmed.2013.04.005; Mah LY, 2012, AUTOPHAGY, V8, P18, DOI 10.4161/auto.8.1.18077; Marisa L, 2013, PLOS MED, V10, DOI 10.1371/journal.pmed.1001453; Matsuyama T, 2010, INT J CANCER, V127, P2292, DOI 10.1002/ijc.25256; Mieczkowski J, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0041541; Molnar B, 2018, BMC CANCER, V18, DOI 10.1186/s12885-018-4609-x; Nikolouzakis TK, 2018, ONCOL REP, V39, P2455, DOI 10.3892/or.2018.6330; Okato A, 2016, INT J ONCOL, V49, P111, DOI 10.3892/ijo.2016.3522; Okita Akira, 2018, Oncotarget, V9, P18698, DOI 10.18632/oncotarget.24617; Qu XP, 2003, J CLIN INVEST, V112, P1809, DOI 10.1172/JCI200320039; Rahman M, 2015, BIOINFORMATICS, V31, P3666, DOI 10.1093/bioinformatics/btv377; Rodchenkov I, 2020, NUCLEIC ACIDS RES, V48, pD489, DOI 10.1093/nar/gkz946; Sabates-Beliver J, 2007, MOL CANCER RES, V5, P1263, DOI 10.1158/1541-7786.MCR-07-0267; Sandberg R, 2007, BMC BIOINFORMATICS, V8, DOI 10.1186/1471-2105-8-48; Sarafian VS, 2018, APMIS, V126, P657, DOI 10.1111/apm.12856; Schlicker A, 2012, BMC MED GENOMICS, V5, DOI 10.1186/1755-8794-5-66; Siegel RL, 2017, CA-CANCER J CLIN, V67, P177, DOI 10.3322/caac.21395; Sveen A, 2018, CLIN CANCER RES, V24, P794, DOI 10.1158/1078-0432.CCR-17-1234; Sweeney T.E., 2015, SCI REP, V5, P1; Takeda M, 2019, CANCER RES, V79, P1426, DOI 10.1158/0008-5472.CAN-18-2192; Thorsson V, 2018, IMMUNITY, V48, P812, DOI 10.1016/j.immuni.2018.03.023; Tsuji S, 2012, BRIT J CANCER, V106, P126, DOI 10.1038/bjc.2011.505; Valcz G, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0106143; Wang QQ, 2017, ONCOL LETT, V14, P4729, DOI 10.3892/ol.2017.6757; Welch HG, 2016, NEW ENGL J MED, V374, P1605, DOI 10.1056/NEJMp1600448; Yang X, 2015, CELL BIOSCI, V5, DOI 10.1186/s13578-015-0005-2; Young JP, 2015, J GASTROEN HEPATOL, V30, P6, DOI 10.1111/jgh.12792; Yun CW, 2018, INT J MOL SCI, V19, DOI 10.3390/ijms19113466; Zhou Z, 2019, FRONT ONCOL, V9, DOI 10.3389/fonc.2019.00878	66	1	1	0	2	MDPI	BASEL	ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND		1422-0067		INT J MOL SCI	Int. J. Mol. Sci.	OCT	2020	21	19							7101	10.3390/ijms21197101			14	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	OO1QM	WOS:000587161100001	32993062	Green Published, gold			2022-04-25	
J	Sun, C; Wang, FJ; Zhang, HG; Xu, XZ; Jia, RC; Yao, L; Qiao, PF				Sun, Chen; Wang, Fu-Jing; Zhang, Hao-Gang; Xu, Xun-Zheng; Jia, Rui-Chun; Yao, Lei; Qiao, Peng-Fei			miR-34a mediates oxaliplatin resistance of colorectal cancer cells by inhibiting macroautophagy via transforming growth factor-beta/Smad4 pathway	WORLD JOURNAL OF GASTROENTEROLOGY			English	Article						miR-34a; Oxaliplatin; Colorectal cancer; Macroautophagy; Transforming growth factor-alpha/Smad pathway	MESENCHYMAL TRANSITION; AUTOPHAGY; 5-FLUOROURACIL; MICRORNAS	AIM To investigate whether microRNA (miR)-34a mediates oxaliplatin (OXA) resistance of colorectal cancer (CRC) cells by inhibiting macroautophagy via the transforming growth factor (TGF)-alpha/Smad4 pathway. METHODS miR-34a expression levels were detected in CRC tissues and CRC cell lines by quantitative real-time polymerase chain reaction. Computational search, functional luciferase assay and western blotting were used to demonstrate the downstream target of miR-34a in CRC cells. Cell viability was measured with Cell Counting Kit-8. Apoptosis and macroautophagy of CRC cells were analyzed by flow cytometry and transmission electron microscopy, and expression of beclin I and LC3-II was detected by western blotting. RESULTS Expression of miR-34a was significantly reduced while expression of TGF-beta and Smad4 was increased in CRC patients treated with OXA-based chemotherapy. OXA treatment also resulted in decreased miR-34a levels and increased TGF-beta and Smad4 levels in both parental cells and the OXA-resistant CRC cells. Activation of macroautophagy contributed to OXA resistance in CRC cells. Expression levels of Smad4 and miR-34a in CRC patients had a significant inverse correlation and overexpressing miR-34a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-alpha/Smad4 pathway. OXA-induced downregulation of miR-34a and increased drug resistance by activating macroautophagy in CRC cells. CONCLUSION miR-34a mediates OXA resistance of CRC by inhibiting macroautophagy via the TGF-alpha/Smad4 pathway.	[Sun, Chen; Wang, Fu-Jing; Zhang, Hao-Gang; Xu, Xun-Zheng; Yao, Lei; Qiao, Peng-Fei] Harbin Med Univ, Affiliated Hosp 2, Dept Gen Surg, Harbin 150086, Heilongjiang Pr, Peoples R China; [Jia, Rui-Chun] Harbin Med Univ, Affiliated Hosp 2, Dept Blood Transfus, Harbin 150086, Heilongjiang Pr, Peoples R China		Qiao, PF (corresponding author), Harbin Med Univ, Affiliated Hosp 2, Dept Gen Surg, Harbin 150086, Heilongjiang Pr, Peoples R China.	lunwenqpf@126.com			Science Foundation of Education Department of Heilongjiang Province, China [12541430]	Supported by Science Foundation of Education Department of Heilongjiang Province, China, no. 12541430.	Bartel DP, 2009, CELL, V136, P215, DOI 10.1016/j.cell.2009.01.002; Burada F, 2015, WORLD J GASTRO ONCOL, V7, P271, DOI 10.4251/wjgo.v7.i11.271; Duncan C, 2010, AUTOPHAGY, V6, P312, DOI 10.4161/auto.6.2.11139; He CJ, 2015, ONCOTARGET, V6, P28867, DOI 10.18632/oncotarget.4814; Kenific CM, 2015, TRENDS CELL BIOL, V25, P37, DOI 10.1016/j.tcb.2014.09.001; Li GD, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0035895; Li HH, 2015, ONCOTARGET, V6, P14026, DOI 10.18632/oncotarget.4334; Lubner SJ, 2010, CLIN COLORECTAL CANC, V9, P157, DOI 10.3816/CCC.2010.n.021; Lv L, 2016, TUMOR BIOL, V37, P8811, DOI 10.1007/s13277-015-4755-6; Matamala N, 2015, CLIN CHEM, V61, P1098, DOI 10.1373/clinchem.2015.238691; Meyerhardt JA, 2005, NEW ENGL J MED, V352, P476, DOI 10.1056/NEJMra040958; Pan BZ, 2015, ONCOTARGET, V6, P32805, DOI 10.18632/oncotarget.5352; Qiao PF, 2015, WORLD J GASTROENTERO, V21, P12822, DOI 10.3748/wjg.v21.i45.12822; Qiao PF, 2015, BMC CANCER, V15, DOI 10.1186/s12885-015-1359-x; Ranadive IN, 2014, CURR COLORECT CANC R, V10, P84, DOI 10.1007/s11888-013-0201-6; Sostres Carlos, 2014, World J Gastrointest Pharmacol Ther, V5, P40, DOI 10.4292/wjgpt.v5.i1.40; Suzuki HI, 2010, AUTOPHAGY, V6, P645, DOI 10.4161/auto.6.5.12046; Toden S, 2016, ONCOTARGET, V7, P16158, DOI 10.18632/oncotarget.7567; Ung L, 2014, CLIN TRANSL ONCOL, V16, P425, DOI 10.1007/s12094-013-1154-6; Welch C, 2007, ONCOGENE, V26, P5017, DOI 10.1038/sj.onc.1210293; White E, 2015, J CLIN INVEST, V125, P42, DOI 10.1172/JCI73941; Yang AD, 2006, CLIN CANCER RES, V12, P4147, DOI 10.1158/1078-0432.CCR-06-0038; Yang HZ, 2015, CANCER LETT, V361, P128, DOI 10.1016/j.canlet.2015.02.045; Zhou JY, 2014, CANCER LETT, V351, P265, DOI 10.1016/j.canlet.2014.06.010; Zhou YF, 2014, MOL ONCOL, V8, P83, DOI 10.1016/j.molonc.2013.09.004	25	73	76	1	3	BAISHIDENG PUBLISHING GROUP INC	PLEASANTON	8226 REGENCY DR, PLEASANTON, CA 94588 USA	1007-9327	2219-2840		WORLD J GASTROENTERO	World J. Gastroenterol.	MAR 14	2017	23	10					1816	1827		10.3748/wjg.v23.i10.1816			12	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	EN4AB	WOS:000395948200010	28348487	hybrid, Green Submitted, Green Published			2022-04-25	
J	Domart, MC; Degli Esposti, D; Sebagh, M; Olaya, N; Harper, F; Pierron, G; Franc, B; Tanabe, KK; Debuire, B; Azoulay, D; Brenner, C; Lemoine, A				Domart, Marie-Charlotte; Degli Esposti, Davide; Sebagh, Mylene; Olaya, Natalia; Harper, Francis; Pierron, Gerard; Franc, Brigitte; Tanabe, Kenneth K.; Debuire, Brigitte; Azoulay, Daniel; Brenner, Catherine; Lemoine, Antoinette			Concurrent induction of necrosis, apoptosis, and autophagy in ischemic preconditioned human livers formerly treated by chemotherapy	JOURNAL OF HEPATOLOGY			English	Article						Cell death; Ischemia/reperfusion; Ischemic preconditioning; Chemotherapy; Bcl-2; Beclin-1; Autophagy; Liver	MOUSE-LIVER; PREOPERATIVE CHEMOTHERAPY; REPERFUSION INJURY; COLORECTAL-CANCER; CELL-DEATH; IN-VIVO; BCL-2; METASTASES; OXALIPLATIN; MECHANISMS	Background/Aims: Liver pathology induced by chemotherapy (steatosis or vascular injury) is known to increase the liver's sensitivity to ischemia/reperfusion (I/R) injury, thereby increasing morbidity and mortality after liver resection. Our aim was to assess whether ischemic preconditioning (IP) reduces I/R injury to livers with chemotherapy-induced pathology. Methods: We analyzed a series of livers from patients treated with chemotherapy for colorectal cancer who underwent IP (n = 30) or not (n = 31) before hepatectomy. All but one of the livers exhibited chemotherapy-induced steatosis and/or peliosis before the I/R insult. Results: Necrosis was less frequent (p = 0.038) in livers with IP than in the others. IP had no influence on apoptosis as assessed by terminal transferase uridyl nick-end labeling (TUNEL) assay or caspase-3, -8 and -9 expression. I P induced a twofold increase in B-cell leukemia/lymphoma 2 (Bcl-2; p < 0.05), which was localized to hepatocytes of centrolobular and peliotic areas and colocalized with the autophagy protein beclin-1 in livers with IP, suggesting their coordinated role in autophagy. Increased expression of the phosphorylated Bcl-2 was observed in preconditioned livers and was associated with a decreased immunoprecipitation of beclin-1 and the increased expression of light chain 3 type II (LC3-II). The increased number of autophagic vacuoles seen by electron microscopy confirmed an association of autophagy in chemotherapy-injured livers following I P. However, the differences in protein expression were not reflected in postresection liver-injury tests or measure of patient morbidity. Conclusions: IP is associated with a reduction in necrosis of hepatocytes already damaged by chemotherapy and an activation of autophagy. Bcl-2 and beclin-1 could be major targets in the regulation of cell death during I/R injury. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.	[Domart, Marie-Charlotte; Degli Esposti, Davide; Olaya, Natalia; Debuire, Brigitte; Lemoine, Antoinette] Hop Paul Brousse, AP HP, Serv Biochim & Biol Mol, F-94804 Villejuif, France; [Domart, Marie-Charlotte; Degli Esposti, Davide; Olaya, Natalia] Univ Paris 11, INSERM, Inst Andre Lwoff IFR89, PRES Universud Paris,U602, Villejuif, France; [Degli Esposti, Davide; Lemoine, Antoinette] Univ Paris 11, Fac Pharm, Lab Biochim & Biol Cellulaire, F-92290 Chatenay Malabry, France; [Sebagh, Mylene] Univ Paris 11, AP HP, Hop Paul Brousse, Inst Andre Lwoff,Serv Anat Pathol,Inserm U785, F-94804 Villejuif, France; [Harper, Francis; Pierron, Gerard] Inst Andre Lwoff, Lab Replicat ADN & Ultrastruct Noyau, UPR 1983, Villejuif, France; [Franc, Brigitte] Univ Versailles St Quentin, Hop Ambroise Pare, AP HP, Serv Anat Pathol,PRES Universud Paris, Versailles, France; [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA USA; [Tanabe, Kenneth K.] Harvard Univ, Sch Med, Boston, MA USA; [Azoulay, Daniel] Univ Paris 11, Hop Paul Brousse, AP HP, Ctr Hepatobiliaire, Villejuif, France; [Brenner, Catherine] Univ Versailles St Quentin, CNRS, PRES Univsud Paris, UMR 8159, Versailles, France		Lemoine, A (corresponding author), Hop Paul Brousse, AP HP, Serv Biochim & Biol Mol, 14 Ave Paul Vaillant Couturier, F-94804 Villejuif, France.	antoinette.lemoine@pbr.aphp.fr	Azoulay, Daniel/Q-7887-2018; Degli Esposti, Davide/M-1917-2015; SEBAGH, Mylène/T-7464-2018	Degli Esposti, Davide/0000-0003-1390-4845; Domart, Marie-Charlotte/0000-0002-5703-2922	Ligue Nationale Contre le Cancer (comite de l'Essonne); NRB-Vaincre le Cancer; Groupement Cooperatif de Transplantation de I'lle de France; Colciencias (Colombia)Departamento Administrativo de Ciencia, Tecnologia e Innovacion Colciencias	Marie-Charlotte Dorriart is a fellow of Ligue Nationale Contre le Cancer (comite de l'Essonne). Davide Degli Esposti is a fellow of NRB-Vaincre le Cancer and Groupement Cooperatif de Transplantation de I'lle de France. Natalia Olaya was supported by a grant from Colciencias (Colombia).	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Hepatol.	NOV	2009	51	5					881	889		10.1016/j.jhep.2009.06.028			9	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	519IY	WOS:000271760800007	19765849				2022-04-25	
J	Wu, WB; Gou, H; Dong, JY; Yang, XL; Zhao, YA; Peng, H; Chen, D; Geng, RM; Chen, LH; Liu, J				Wu, Wenbing; Gou, Hui; Dong, Jingying; Yang, Xiaolong; Zhao, Yanan; Peng, Heng; Chen, Dan; Geng, Ruiman; Chen, Lihong; Liu, Ji			Usnic Acid Inhibits Proliferation and Migration through ATM Mediated DNA Damage Response in RKO Colorectal Cancer Cell	CURRENT PHARMACEUTICAL BIOTECHNOLOGY			English	Article						Apoptosis; ATM; autophagy; DNA damage; miR-18a; usnic acid	INDUCED TOXICITY; APOPTOSIS; AUTOPHAGY; TRANSCRIPTION; ACTIVATION; MICRORNAS; MECHANISMS; CARCINOMA; ROS	Background: Usnic Acid (UA), also known as lichenol, has been reported to have inhibitory effects on a variety of cancer cells, but its specific mechanism remained to be elucidated. Tumor chemotherapy drugs, especially DNA damage chemotherapeutic drugs, target Chromosomal DNA, but their spontaneous and acquired drug resistance are also an urgent problem to be solved. Therefore, drug combination research has become the focus of researchers. Methods: Here, we evaluated the tumor- suppressing molecular mechanism of UA in colorectal cancer cells RKO from the perspective of the ATM-mediated DNA damage signaling pathway through H2O2 simulating DNA damage chemotherapeutic drugs. CCK8 cell proliferation assay was used to determine the inhibition of RKO cells by hydrogen peroxide and UA alone or in combination, and wound healing assay was applied to determine the effect of the drug on cell migration. Results: Transfected cells with miRNA18a-5p mimics and inhibitors, MDC and DCFH-DA staining for the measurement of autophagy and ROS, cell cycle and apoptosis were detected by flow cytometry, expressions of microRNA and mRNA were determined by fluorescence quantitative PCR, and protein by Western blot. Discussion: We found that UA can upregulate ATM via miR-18a to activate the DNA damage signaling pathway and inhibit the proliferation and migration of RKO cells in a concentration-dependent manner. Conclusion: At the same time, DNA damage responses, including cell cycle, autophagy, apoptosis and ROS levels, are also regulated by UA. Therefore, UA combined with DNA damage chemotherapeutic drugs may be an effective treatment for cancer.	[Wu, Wenbing; Dong, Jingying; Yang, Xiaolong; Zhao, Yanan; Peng, Heng; Chen, Dan; Geng, Ruiman; Chen, Lihong; Liu, Ji] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Dept Biochem & Mol Biol, 17 Peoples South Rd, Chengdu 610041, Peoples R China; [Wu, Wenbing] Southwest Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Luzhou 646000, Peoples R China; [Gou, Hui] Southwest Med Univ, Dept Pharm, Affiliated Hosp, Luzhou 646000, Peoples R China		Liu, J (corresponding author), Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Dept Biochem & Mol Biol, 17 Peoples South Rd, Chengdu 610041, Peoples R China.	liuji6103@163.com		Geng, Ruiman/0000-0002-9253-9171; wenbing, wu/0000-0002-8132-5100; dong, jingying/0000-0002-3841-1644			Backorova M, 2011, TOXICOL IN VITRO, V25, P37, DOI 10.1016/j.tiv.2010.09.004; Bakkenist CJ, 2003, NATURE, V421, P499, DOI 10.1038/nature01368; Bessadottir M, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0051296; Brisdelli F, 2013, PHYTOTHER RES, V27, P431, DOI 10.1002/ptr.4739; Cadet J, 2014, ARCH BIOCHEM BIOPHYS, V557, P47, DOI 10.1016/j.abb.2014.05.001; Cardarelli M, 1997, CELL MOL LIFE SCI, V53, P667, DOI 10.1007/s000180050086; Carrassa L, 2017, CANCER TREAT REV, V60, P139, DOI 10.1016/j.ctrv.2017.08.013; Chen S, 2017, ARCH TOXICOL, V91, P1293, DOI 10.1007/s00204-016-1775-y; Chen S, 2014, TOXICOL SCI, V142, P33, DOI 10.1093/toxsci/kfu154; Einarsdottir E, 2010, PLANTA MED, V76, P969, DOI 10.1055/s-0029-1240851; Geng XG, 2018, MED SCI MONITOR, V24, DOI 10.12659/MSM.908568; Guo Z, 2010, SCIENCE, V330, P517, DOI 10.1126/science.1192912; Halliwell B, 2007, BIOCHEM J, V401, P1, DOI 10.1042/BJ20061131; Krishna YR, 2011, CAN J GASTROENTEROL, V25, P157; Li LL, 2015, CELL MOL NEUROBIOL, V35, P615, DOI 10.1007/s10571-015-0166-x; Liu MZ, 2013, GENE DEV, V27, P2543, DOI 10.1101/gad.224170.113; Lord CJ, 2012, NATURE, V481, P287, DOI 10.1038/nature10760; Machado NM, 2019, J TOXICOL ENV HEAL A, V82, P401, DOI 10.1080/15287394.2019.1613274; Maciag-Dorszynska M, 2014, FEMS MICROBIOL LETT, V353, P57, DOI 10.1111/1574-6968.12409; Meschini S, 2008, AUTOPHAGY, V4, P1020, DOI 10.4161/auto.6952; Pires RH, 2012, ANTIMICROB AGENTS CH, V56, P595, DOI 10.1128/AAC.05348-11; Polewska J, 2012, POSTEP HIG MED DOSW, V66, P921, DOI 10.5604/17322693.1021109; Qased A, 2013, MOL MED REP, V7, P559, DOI 10.3892/mmr.2012.1214; Rancoule C, 2017, B CANCER, V104, P962, DOI 10.1016/j.bulcan.2017.09.006; Redondo-Blanco S, 2017, FRONT PHARMACOL, V8, DOI 10.3389/fphar.2017.00109; Schieber M, 2014, CURR BIOL, V24, pR453, DOI 10.1016/j.cub.2014.03.034; Siegel R, 2014, CA-CANCER J CLIN, V64, P104, DOI 10.3322/caac.21220; Simizu S, 1998, J BIOL CHEM, V273, P26900, DOI 10.1074/jbc.273.41.26900; Singh N, 2013, NUTR CANCER, V65, P36, DOI 10.1080/01635581.2013.785007; Song LB, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0025454; Tan H, 2019, EBIOMEDICINE, V43, P82, DOI 10.1016/j.ebiom.2019.03.082; Tian H, 2015, CANCER LETT, V358, P8, DOI 10.1016/j.canlet.2014.12.038; Valko M, 2004, MOL CELL BIOCHEM, V266, P37, DOI 10.1023/B:MCBI.0000049134.69131.89; Vasudevan S, 2007, SCIENCE, V318, P1931, DOI 10.1126/science.1149460; Wu CW, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0057036; Wu W, 2018, EVID-BASED COMPL ALT, V2018, DOI 10.1155/2018/5149436; Wu XJ, 2007, CANCER BIOL THER, V6, P646, DOI 10.4161/cbt.6.5.4092; Xiao M, 2017, RNA BIOL, V14, P1326, DOI 10.1080/15476286.2015.1112487; Yurdacan B, 2019, J PHARM PHARMACOL, V71, P1119, DOI 10.1111/jphp.13097; Zhang YJ, 2014, RNA, V20, P1878, DOI 10.1261/rna.045633.114	40	3	3	6	19	BENTHAM SCIENCE PUBL LTD	SHARJAH	EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES	1389-2010	1873-4316		CURR PHARM BIOTECHNO	Curr. Pharm. Biotechnol.		2021	22	8					1129	1138		10.2174/1389201021666201002155955			10	Biochemistry & Molecular Biology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy	SF0KU	WOS:000652454500011	33006536				2022-04-25	
J	Wang, J; Wang, J; Li, L; Feng, L; Wang, YR; Wang, Z; Tan, NH				Wang, Jing; Wang, Jia; Li, Ling; Feng, Li; Wang, Yu-Rong; Wang, Zhe; Tan, Ning-Hua			RA-XII, a bicyclic hexapeptidic glucoside isolated from Rubia yunnanensis Diels, exerts antitumor activity by inhibiting protective autophagy and activating Akt-mTOR pathway in colorectal cancer cells	JOURNAL OF ETHNOPHARMACOLOGY			English	Article						Rubia yunnanensis Diels; Cyclopeptide; RA-XII; Colorectal cancer; Antitumor mechanism		Ethnopharmacological relevance: The roots of Rubia yunnanensis Diels (Chinese name 'Xiao-Hong-Shen'), a traditional Chinese medicine native to Yunnan province (China), have a long history of use for treating several diseases, such as tuberculosis, rheumatism and cancers. A bicyclic hexapeptidic glucoside named RA-XII was isolated from R. yunnanensis, which has been reported to exert anti-inflammatory and antitumor activities. Aim of the study: This study was designed to investigate the antitumor activity and potential mechanism of RA-XII on colorectal cancer (CRC) cell lines. Materials and methods: Sulforhodamine B assay, clonogenic assay and cell cycle analysis were conducted to assess the anti-proliferative activity of RA-XII on CRC cells. GFP-LC3B plasmid transfection, MDC and AO staining assays, cathepsin activity assay, and siRNAs against several genes were used to investigate the effect of RA-XII on autophagy. Western blotting was used to examine the expression levels of proteins associated with cell cycle arrest, apoptosis and autophagy. Human CRC xenograft-bearing BALB/c nude mice were used to evaluate the antitumor effect of RA-XII in vivo. Results: RA-XII showed favorable antineoplastic activity in SW620 and HT29 cells in vitro and in vivo. RA-XII did not induce apoptosis indicated by no obvious changes on mitochondrial membrane potential and apoptosisrelated marker proteins in SW620 or HT29 cells. Treatment of RA-XII inhibited the formation of autophagosomes, which is implied by the GFP-LC3 fluorescent dots, MDC-stained autophagic vesicles and LC3 protein expression. It was indicated that RA-XII suppressed autophagy by regulating several signaling pathways including mTOR and NF-kappa B pathways. Pharmacological or genetic inhibition of autophagy could enhance the cytotoxicity of RA-XII while autophagy inducer could rescue RA-XII-induced cell death. Besides, RA-XII could increase the susceptibility of CRC cells to bortezomib. Conclusion: Our study demonstrated that RA-XII exerted antitumor activity independent of apoptosis, and suppressed protective autophagy by regulating mTOR and NF-kappa B pathways in SW620 and HT29 cell lines, which suggested that RA-XII is a key active ingredient for the cancer treatment of Rubia yunnanensis and possesses a promising prospect as an autophagy inhibitor for CRC therapy.	[Wang, Jing; Wang, Jia; Li, Ling; Feng, Li; Wang, Yu-Rong; Wang, Zhe; Tan, Ning-Hua] China Pharmaceut Univ, Sch Tradit Chinese Pharm, Dept TCMs Pharmaceut, Nanjing 211198, Peoples R China		Wang, Z; Tan, NH (corresponding author), China Pharmaceut Univ, Sch Tradit Chinese Pharm, Dept TCMs Pharmaceut, Nanjing 211198, Peoples R China.	18851107621@163.com; 1731020094@stu.cpu.edu.cn; 1821020435@stu.cpu.edu.cn; cpu_fengli2012@163.com; yurong1987213@163.com; wangzhe@cpu.edu.cn; nhtan@cpu.edu			National New Drug Innovation Major Project of Ministry of Science and Technology of China [2017ZX09309027]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21702231, 81803572]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20170745]; Program of Innovative Research Team of Jiangsu Province; "Double First-Class" Project of China Pharmaceutical University [CPU2018GF05]	This work was supported by the National New Drug Innovation Major Project of Ministry of Science and Technology of China (2017ZX09309027), the National Natural Science Foundation of China (21702231, 81803572), the Natural Science Foundation of Jiangsu Province (BK20170745), the Program of Innovative Research Team of Jiangsu Province, and the "Double First-Class" Project of China Pharmaceutical University (CPU2018GF05).	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Ethnopharmacol.	FEB 10	2021	266								113438	10.1016/j.jep.2020.113438			13	Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine	PE0JX	WOS:000598060900005	33017635				2022-04-25	
J	Chen, LX; Sun, LB; Dai, XF; Li, T; Yan, XJ; Zhang, YT; Xiao, HX; Shen, XD; Huang, G; Xiang, W; Zhang, Y; Tan, DH; Yang, SM; Nie, YZ; Huang, XQ; Lian, JQ; He, FT				Chen, Lingxi; Sun, Liangbo; Dai, Xufang; Li, Tao; Yan, Xiaojing; Zhang, Yueting; Xiao, Hanxi; Shen, Xiaodong; Huang, Gang; Xiang, Wei; Zhang, Yan; Tan, Dehong; Yang, Shiming; Nie, Yongzhan; Huang, Xuequan; Lian, Jiqin; He, Fengtian			LncRNA CRNDE Promotes ATG4B-Mediated Autophagy and Alleviates the Sensitivity of Sorafenib in Hepatocellular Carcinoma Cells	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY			English	Article						hepatocellular carcinoma; CRNDE; ATG4B; autophagy; sorafenib	LONG-NONCODING RNA; CANCER; CHEMOSENSITIVITY; PROLIFERATION; EXPRESSION; MECHANISM; INVASION; SPONGE; ATG4B; 5-FU	Autophagy is closely related to the growth and drug resistance of cancer cells, and autophagy related 4B (ATG4B) performs a crucial role in the process of autophagy. The long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) promotes the progression of hepatocellular carcinoma (HCC), but it is unclear whether the tumor-promoting effect of CRNDE is associated with the regulation of ATG4B and autophagy. Herein, we for the first time demonstrated that CRNDE triggered autophagy via upregulating ATG4B in HCC cells. Mechanistically, CRNDE enhanced the stability of ATG4B mRNA by sequestrating miR-543, leading to the elevation of ATG4B and autophagy in HCC cells. Moreover, sorafenib induced CRNDE and ATG4B as well as autophagy in HCC cells. Knockdown of CRNDE sensitized HCC cells to sorafenib in vitro and in vivo. Collectively, these results reveal that CRNDE drives ATG4B-mediated autophagy, which attenuates the sensitivity of sorafenib in HCC cells, suggesting that the pathway CRNDE/ATG4B/autophagy may be a novel target to develop sensitizing measures of sorafenib in HCC treatment.	[Chen, Lingxi; Li, Tao; Yan, Xiaojing; Zhang, Yueting; Xiao, Hanxi; Shen, Xiaodong; Huang, Gang; Xiang, Wei; Zhang, Yan; Lian, Jiqin; He, Fengtian] Army Med Univ, Coll Basic Med Sci, Dept Biochem & Mol Biol, Chongqing, Peoples R China; [Sun, Liangbo; Lian, Jiqin] Army Med Univ, Fac Pharm & Lab Med, Dept Clin Biochem, Chongqing, Peoples R China; [Dai, Xufang] Chongqing Normal Univ, Coll Educ Sci, Chongqing, Peoples R China; [Tan, Dehong] Army Med Univ, Southwest Hosp, Inst Hepatopancreatobiliary Surg, Chongqing, Peoples R China; [Yang, Shiming] Army Med Univ, Xinqiao Hosp, Dept Gastroenterol, Chongqing, Peoples R China; [Nie, Yongzhan] Air Force Med Univ, State Key Lab Canc Biol, Xian, Peoples R China; [Huang, Xuequan] Army Med Univ, Southwest Hosp, Ctr Minimally Invas Intervent, Chongqing, Peoples R China		Lian, JQ; He, FT (corresponding author), Army Med Univ, Coll Basic Med Sci, Dept Biochem & Mol Biol, Chongqing, Peoples R China.; Lian, JQ (corresponding author), Army Med Univ, Fac Pharm & Lab Med, Dept Clin Biochem, Chongqing, Peoples R China.; Huang, XQ (corresponding author), Army Med Univ, Southwest Hosp, Ctr Minimally Invas Intervent, Chongqing, Peoples R China.	hxuequan@163.com; lianjiqin@sina.com; hefengtian66@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81872024, 31671464, 82073300]; Natural Science Foundation of ChongqingNatural Science Foundation of Chongqing [cstc2017jcyjBX0079, cstc2018jcyjA2018]; Open Fund Research Projects of the State Key Laboratory of Cancer Biology of Air Force Medical University [CBSKL2019ZDKF07]; Basic and Clinical Integration Research Project of Army Medical University [2019JCLC04]	This study was supported by the National Natural Science Foundation of China (81872024, 31671464, and 82073300), the Natural Science Foundation of Chongqing (cstc2017jcyjBX0079 and cstc2018jcyjA2018), the Open Fund Research Projects of the State Key Laboratory of Cancer Biology of Air Force Medical University (CBSKL2019ZDKF07), and the Basic and Clinical Integration Research Project of Army Medical University (2019JCLC04).	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Cell. Dev. Biol.	AUG 2	2021	09								687524	10.3389/fcell.2021.687524			16	Cell Biology; Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Developmental Biology	UA6DC	WOS:000685249400001	34409031	Green Published, gold			2022-04-25	
J	Kim, MS; Song, SY; Lee, JY; Yoo, NJ; Lee, SH				Kim, Min Sung; Song, Sang Yong; Lee, Ji Youl; Yoo, Nam Jin; Lee, Sug Hyung			Expressional and mutational analyses of ATG5 gene in prostate cancers	APMIS			English	Article						ATG5; mutation; expression; prostate cancer; autophagy	AUTOPHAGY-RELATED GENE; MICROSATELLITE INSTABILITY; COLORECTAL CANCERS; CELL-DEATH; BECLIN-1; APOPTOSIS; TUMORIGENESIS; DISRUPTION; CARCINOMAS; THERAPY	Autophagy is an evolutionarily conserved mechanism that plays important roles in both cell death and cell survival. ATG5 is an essential constituent for autophagosome formation, which sequesters cytoplasmic materials before lysosomal delivery. Although both cell death and survival are important in cancer development, the role of autophagy in prostate cancer development remains unclear. The aim of this study was to see whether alterations of ATG5 protein expression and somatic mutations of the ATG5 gene are found in prostate cancers. In the present study, we analyzed ATG5 protein expression in 107 prostate carcinomas by immunohistochemistry; additionally, we assayed the presence of ATG5 somatic mutations in 45 prostate carcinomas by single-strand conformation polymorphism. Immunostaining of ATG5 in normal prostate cells was observed in 44.9% of the cases, whereas in prostate intraepithelial neoplasm (PIN) and prostate cancer cells, ATG5 was observed in 100% and 89.7% of the cases, respectively. Cytoplasmic expression of ATG5 that might be related to autophagy was seen in PIN (100%) and cancers (83.2%), but not in normal cells (0%). ATG5 expression was not associated with any of the pathologic characteristics, including size of the cancers, age, Gleason score, and stage. As for the ATG5 gene, we found no somatic mutations in the prostate cancers. In this study, we analyzed ATG5 expression and mutation in prostate cancers, and found that ATG5 expression was altered in prostate cancers. The expression of ATG5, especially in the cytoplasm, in the prostate cancers compared with normal prostate cells suggested that overexpression of this protein may be related to autophagy and might play a role in prostate tumorigenesis.	[Kim, Min Sung; Yoo, Nam Jin; Lee, Sug Hyung] Catholic Univ Korea, Dept Pathol, Coll Med, Seoul 137701, South Korea; [Song, Sang Yong] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea; [Lee, Ji Youl] Catholic Univ Korea, Dept Urol, Coll Med, Seoul 137701, South Korea		Lee, SH (corresponding author), Catholic Univ Korea, Dept Pathol, Coll Med, 505 Banpo Dong, Seoul 137701, South Korea.	suhulee@catholic.ac.kr			Ministry for Health, Welfare and Family Affairs of KoreaMinistry of Health & Welfare, Republic of Korea [A100098]	This study was supported by a grant from Ministry for Health, Welfare and Family Affairs of Korea (A100098).	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J	Uscatu, CD; Mixich, F; Dumitrescu, TV; Nicoli, ER; Deliu, IC; Man, GM; Plesea, IE				Uscatu, Constantin Daniel; Mixich, Francisc; Dumitrescu, Theodor Viorel; Nicoli, Elena-Raluca; Deliu, Ionela Cristina; Man, George Mihail; Plesea, Iancu Emil			The influence of irradiation on autophagy process in normal and malignant colorectal epithelia	ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY			English	Article						colorectal cancer; autophagy; LC3; preoperative irradiation	CANCER CELLS; PATTERNS	Aim: The authors assessed the influence of preoperative radiotherapy on autophagy process using a quantitative assessment of LC3 expression on both normal and tumoral colorectal tissues. Materials and Methods: Normal and malignant tissue samples were taken from 50 patients that underwent surgery for colorectal adenocarcinoma of which 11 received preoperative radiotherapy. Tissue samples were included in paraffin and sections were immunomarked for LC3 expression. LC3 percentage was assessed with dedicated software on 10 randomly selected fields with 40x objective from both normal and malignant tissue samples of each patient. The resulting data were assessed and compared with a statistical apparatus. Results: LC3 was overexpressed in tumoral tissue as compared with normal one. The LC3 percentage is different from person to person and the higher it is in normal epithelium, the higher will be in tumoral epithelium of the same person, regardless the irradiation. The LC3 expression levels are decreasing from tumoral non-irradiated epithelia to normal irradiated epithelia. LC3 expression in tumoral cells is granular, with particular perinuclear disposal and often "annular' pattern. Conclusions: The autophagy process has a basal level in the normal tissue, with interindividual variability. The autophagy process proved to be upregulated in the tumoral cells, with a particular morphological expression, namely the presence of cytoplasmic coarse granules disposed in an "annular' pattern. Preoperative radiotherapy is downregulating the autophagy process both in normal and tumoral tissue but to a lesser extent in the latter.	[Uscatu, Constantin Daniel; Mixich, Francisc; Nicoli, Elena-Raluca] Univ Med & Pharm Craiova, Dept Cellular & Mol Biol, Craiova 200349, Romania; [Uscatu, Constantin Daniel; Plesea, Iancu Emil] Emergency Cty Hosp, Dept Pathol, 1 Tabaci St, Craiova 200642, Romania; [Dumitrescu, Theodor Viorel] Emergency Cty Hosp, Dept Surg, Craiova 200642, Romania; [Deliu, Ionela Cristina] Univ Med & Pharm Craiova, Dept Gastroenterol, Craiova 200349, Romania; [Man, George Mihail] Emergency Cty Hosp, Dept Pathol, Pitesti, Romania; [Plesea, Iancu Emil] Univ Med & Pharm Craiova, Dept Pathol, 2 Petru Rares St, Craiova 200349, Romania		Plesea, IE (corresponding author), Emergency Cty Hosp, Dept Pathol, 1 Tabaci St, Craiova 200642, Romania.; Plesea, IE (corresponding author), Univ Med & Pharm Craiova, Dept Pathol, 2 Petru Rares St, Craiova 200349, Romania.	pie1956@yahoo.com	Nicoli, Elena-Raluca/F-3968-2011	Nicoli, Elena-Raluca/0000-0002-5545-630X; Dumitrescu, Theodor Viorel/0000-0002-2485-7821; Calota, Firmilian/0000-0002-2689-5477	European Social Fund, Human Resources Development Operational ProgramEuropean Social Fund (ESF) [POSDRU/159/1.5/136893]	This paper was published under the frame of European Social Fund, Human Resources Development Operational Program 2007-2013, Project No. POSDRU/159/1.5/136893.	Giatromanolaki A, 2010, J CLIN PATHOL, V63, P867, DOI 10.1136/jcp.2010.079525; Guo GF, 2011, WORLD J GASTROENTERO, V17, P4779, DOI 10.3748/wjg.v17.i43.4779; Holt SV, 2011, TOXICOL PATHOL, V39, P516, DOI 10.1177/0192623310396903; Koukourakis MI, 2010, BRIT J CANCER, V103, P1209, DOI 10.1038/sj.bjc.6605904; Ladoire S, 2012, AUTOPHAGY, V8, P1175, DOI 10.4161/auto.20353; Lebovitz CB, 2012, CLIN CANCER RES, V18, P1214, DOI 10.1158/1078-0432.CCR-11-2465; Rosenfeldt MT, 2012, AUTOPHAGY, V8, P963, DOI 10.4161/auto.20186; Sato K, 2007, CANCER RES, V67, P9677, DOI 10.1158/0008-5472.CAN-07-1462; Zheng Hai-yang, 2012, Cancer Biology Medicine, V9, P105, DOI 10.3969/j.issn.2095-3941.2012.02.004	9	0	0	0	4	EDITURA ACAD ROMANE	BUCURESTI	CALEA 13 SEPTEMBRIE NR 13, SECTOR 5, BUCURESTI 050711, ROMANIA	1220-0522			ROM J MORPHOL EMBRYO	Rom. J. Morphol. Embryol.		2016	57	1					227	232					6	Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Developmental Biology	DM0PR	WOS:000376048800029	27151712				2022-04-25	
J	Lee, G; Liang, CY; Park, G; Jang, C; Jung, JU; Chung, J				Lee, Gina; Liang, Chengyu; Park, Gihyun; Jang, Cholsoon; Jung, Jae U.; Chung, Jongkyeong			UVRAG is required for organ rotation by regulating Notch endocytosis in Drosophila	DEVELOPMENTAL BIOLOGY			English	Article						UVRAG; Organ rotation; Vesicle trafficking; Notch endocytosis; Left-right body asymmetry	LEFT-RIGHT ASYMMETRY; PROGRAMMED CELL-DEATH; UNCONVENTIONAL MYOSIN; SIGNALING PATHWAY; TUMOR SUPPRESSORS; NODAL EXPRESSION; ENDOSOMAL ENTRY; MALE TERMINALIA; DOWN-REGULATION; COLON-CANCER	Heterotaxy characterized by abnormal left-right body asymmetry causes diverse congenital anomalies. Organ rotation is a crucial developmental process to establish the left-right patterning during animal development. However, the molecular basis of how organ rotation is regulated is poorly understood. Here we report that Drosophila UV-resistance associated gene (UVRAG), a tumor suppressor that regulates autophagy and endocytosis, plays unexpected roles in controlling organ rotation. Loss-of-function mutants of UVRAG show seriously impaired organ rotation phenotypes, which are associated with defects in endocytic trafficking rather than autophagy. Blunted endocytic degradation by UVRAG deficiency causes endosomal accumulation of Notch, resulting in abnormally enhanced Notch activity. Knockdown of Notch itself or expression of a dominant negative form of Notch transcriptional co-activator Mastermind is sufficient to rescue the rotation defect in UVRAG mutants. Consistently. UVRAG-mutated heterotaxy patient cells also display highly increased Notch protein levels. These results suggest evolutionarily conserved roles of UVRAG in organ rotation by regulating Notch endocytic degradation. (C) 2011 Elsevier Inc. All rights reserved.	[Liang, Chengyu; Jung, Jae U.] Univ So Calif, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA; [Lee, Gina; Park, Gihyun; Chung, Jongkyeong] Seoul Natl Univ, Natl Creat Res Initiat Ctr, Seoul 151742, South Korea; [Lee, Gina; Park, Gihyun; Chung, Jongkyeong] Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea; [Lee, Gina; Park, Gihyun; Jang, Cholsoon; Chung, Jongkyeong] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea; [Chung, Jongkyeong] Seoul Natl Univ, Inst Mol Biol & Genet, Seoul 151742, South Korea		Jung, JU (corresponding author), Univ So Calif, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA.	jaeujung@usc.edu; jkc@snu.ac.kr		LIANG, CHENGYU/0000-0001-6082-2143	National Creative Research Initiatives ProgramMinistry of Education, Science and Technology, Republic of Korea [2010-0018291]; Priority Research Centers Program [2009-0094022]; Ministry of Education, Science, and Technology (MEST) of KoreaMinistry of Education, Science and Technology, Republic of Korea; U.S. Public Health ServiceUnited States Department of Health & Human ServicesUnited States Public Health Service [CA82057, CA91819, CA31363, CA115284, AI073099]; Fletcher Jones Foundation; Hastings Foundation; Korean GRL Program [K20815000001]; Lymphoma and Leukemia Society of USA; Wright Foundation; Baxter Foundation;  [AI083841];  [CA140964]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA031363, R21CA161436, R01CA082057, R01CA091819, R01CA140964, R01CA115284] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01AI073099, R21AI083841] Funding Source: NIH RePORTER	We thank Drs. Ben-Zion Shilo, Denise Montell, Ernesto Sanchez-Herrero, Gary Struhl, Harald Stenmark, Hirofumi Ohashi, Hugo Bellen, Jaeseob Kim, Masayuki Miura, Pernille Rorth, Tetsuya Tabata and Thomas Neufeld for reagents and Drosophila lines. We are grateful to Drs. Kyung-Ok Cho, Kwang-Wook Choi and Young-Yun Kong for helpful discussion and kind support. We thank Bloomington Stock Center, Developmental Studies Hybridoma Bank, Drosophila Genetic Resource Center, Drosophila Genomics Resource Center, National Institute of Genetics and VDRC Stock Center for Drosophila stocks and antibodies, and Korea Basic Science Institute and National Instrumentation Center for Environmental Management (Seoul National University) for electron microscopic analysis. This work was supported by the National Creative Research Initiatives Program (2010-0018291) to J.C. and the Priority Research Centers Program (2009-0094022) to G.L. from the National Research Foundation (NRF) grant funded by the Ministry of Education, Science, and Technology (MEST) of Korea. J.J. was supported by U.S. Public Health Service grants CA82057, CA91819, CA31363, CA115284, AI073099, the Fletcher Jones Foundation, the Hastings Foundation and the Korean GRL Program (K20815000001). C.L was supported by AI083841, CA140964, the Lymphoma and Leukemia Society of USA, the Wright Foundation and the Baxter Foundation.	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Biol.	AUG 15	2011	356	2					588	597		10.1016/j.ydbio.2011.06.024			10	Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Developmental Biology	806JO	WOS:000293803900026	21729695	Green Accepted, Bronze			2022-04-25	
J	Park, SJ; Park, SH; Kim, JO; Kim, JH; Park, SJ; Hwang, JJ; Jin, DH; Jeong, SY; Lee, SJ; Kim, JC; Kim, I; Cho, DH				Park, So Jung; Park, Seong Ho; Kim, Joo-Oh; Kim, Jung Ho; Park, So Jung; Hwang, Jung Jin; Jin, Dong-Hoon; Jeong, Seong-Yun; Lee, Seung Jin; Kim, Jin Cheon; Kim, InKi; Cho, Dong-Hyung			Carnitine sensitizes TRAIL-resistant cancer cells to TRAIL-induced apoptotic cell death through the up-regulation of Bax	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						TRAIL; Resistance; Carnitine; A549; Apoptosis; Sensitization	GENE-EXPRESSION; LIGAND; MITOCHONDRIA; INHIBITION; ACTIVATION; PROTEIN; MCL-1; MECHANISMS; THERAPY; PATHWAY	Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family with apoptosis-inducing activity. Given that TRAIL selectively induces cell death in various tumors but has little or no toxicity to normal cells. TRAIL agonists have been considered as promising anti-cancer therapeutic agents. However, the resistance of many primary tumors and cancer cells to TRAIL poses a challenge. In our present study, we found that carnitine, a metabolite that transfers long-chain fatty acids into mitochondria for beta-oxidation and modulates protein kinase C activity, sensitizes TRAIL-resistant cancer cells to TRAIL. Combination of carnitine and TRAIL was found to synergistically induce apoptotic cell death through caspase activation, which was blocked by a pan caspase inhibitor, but not by an inhibitor of autophagy or an inhibitor of necrosis. The combination of carnitine and TRAIL reversed the resistance to TRAIL in lung cancer cells, colon carcinoma cells, and breast carcinoma cells. We further demonstrate that carnitine, either alone or in combination with TRAIL, enhances the expression of the pro-apoptotic Bcl-2 family protein, Bcl-2-associated X protein (Bax). The downregulation of Bax expression by small interfering RNA reduced caspase activation when cells were treated with TRAIL, and experiments with cells from Bax knockout mice confirmed this result. Taken together, our current results suggest that carnitine can reverse the resistance of cancer cells to TRAIL by up-regulating Bax expression. Thus, a combined delivery of carnitine and TRAIL may represent a new therapeutic strategy to treat TRAIL-resistant cancer cells. (C) 2012 Elsevier Inc. All rights reserved.	[Park, So Jung; Kim, Joo-Oh; Kim, Jung Ho; Cho, Dong-Hyung] Kyung Hee Univ, Grad Sch EW Med Sci, Yongin 446701, Gyeoggi Do, South Korea; [Park, Seong Ho] Hallym Univ, Ilsong Inst Life Sci, Kangwon Do, South Korea; [Park, So Jung; Hwang, Jung Jin; Jin, Dong-Hoon; Jeong, Seong-Yun; Lee, Seung Jin; Kim, InKi] Univ Ulsan, Coll Med, Asan Med Ctr, Asan Inst Med Res, Seoul, South Korea; [Hwang, Jung Jin; Jin, Dong-Hoon; Jeong, Seong-Yun; Lee, Seung Jin; Kim, Jin Cheon] Asan Med Ctr, Inst Innovat Canc Res, Seoul 138736, South Korea; [Kim, Jin Cheon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Surg, Seoul, South Korea		Kim, I (corresponding author), Asan Med Ctr, Asan Inst Med Reserch, Seoul 138736, South Korea.	ik.kim@amc.seoul.kr; dhcho@khu.ac.kr	Hwang, Jung Jin/F-3424-2014		Basic Science Research Program; National Research Foundation, KoreaNational Research Foundation of Korea [2010-0009164]; Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A062254]	This research was supported by the Basic Science Research Program, the National Research Foundation, Korea (2010-0009164), and a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A062254).	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Biophys. Res. Commun.	NOV 9	2012	428	1					185	190		10.1016/j.bbrc.2012.10.038			6	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	043DN	WOS:000311523200032	23068102				2022-04-25	
J	Wei, FZ; Cao, ZY; Wang, X; Wang, H; Cai, MY; Li, TT; Hattori, N; Wang, DL; Du, YP; Song, BY; Cao, LL; Shen, CC; Wang, LN; Wang, HY; Yang, Y; Xie, D; Wang, F; Ushijima, T; Zhao, Y; Zhu, WG				Wei, Fu-Zheng; Cao, Ziyang; Wang, Xi; Wang, Hui; Cai, Mu-Yan; Li, Tingting; Hattori, Naoko; Wang, Donglai; Du, Yipeng; Song, Boyan; Cao, Lin-Lin; Shen, Changchun; Wang, Lina; Wang, Haiying; Yang, Yang; Xie, Dan; Wang, Fan; Ushijima, Toshikazu; Zhao, Ying; Zhu, Wei-Guo			Epigenetic regulation of autophagy by the methyltransferase EZH2 through an MTOR-dependent pathway	AUTOPHAGY			English	Article						autophagy; EZH2; histone modification; MTA2; MTOR pathway	REPRESSIVE COMPLEX 2; HISTONE DEACETYLASE; MI-2/NURD COMPLEX; TUMOR-SUPPRESSOR; CHROMATIN; NURD; METHYLATION; METASTASIS; GENE; RECRUITMENT	Macroautophagy is an evolutionarily conserved cellular process involved in the clearance of proteins and organelles. Although the autophagy regulation machinery has been widely studied, the key epigenetic control of autophagy process still remains unknown. Here we report that the methyltransferase EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) epigenetically represses several negative regulators of the MTOR (mechanistic target of rapamycin [serine/threonine kinase]) pathway, such as TSC2, RHOA, DEPTOR, FKBP11, RGS16 and GPI. EZH2 was recruited to these genes promoters via MTA2 (metastasis associated 1 family, member 2), a component of the nucleosome remodeling and histone deacetylase (NuRD) complex. MTA2 was identified as a new chromatin binding protein whose association with chromatin facilitated the subsequent recruitment of EZH2 to silenced targeted genes, especially TSC2. Downregulation of TSC2 (tuberous sclerosis 2) by EZH2 elicited MTOR activation, which in turn modulated subsequent MTOR pathway-related events, including inhibition of autophagy. In human colorectal carcinoma (CRC) tissues, the expression of MTA2 and EZH2 correlated negatively with expression of TSC2, which reveals a novel link among epigenetic regulation, the MTOR pathway, autophagy induction, and tumorigenesis.	[Wei, Fu-Zheng; Cao, Ziyang; Wang, Xi; Wang, Hui; Wang, Donglai; Du, Yipeng; Song, Boyan; Cao, Lin-Lin; Shen, Changchun; Wang, Lina; Wang, Haiying; Yang, Yang; Zhao, Ying; Zhu, Wei-Guo] Peking Univ, Beijing Key Lab Prot Posttranslat Modificat & Cel, Dept Biochem & Mol Biol,Hlth Sci Ctr,Minist Educ, State Key Lab Nat & Biomimet Drugs,Key Lab Carcin, Beijing 100871, Peoples R China; [Cai, Mu-Yan; Xie, Dan] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China; [Li, Tingting] Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biomed Informat, Beijing 100871, Peoples R China; [Hattori, Naoko; Ushijima, Toshikazu] Natl Canc Ctr, Div Epigen, Tokyo, Japan; [Wang, Fan] Peking Univ, Sch Basic Med Sci, Dept Radiat Med, Beijing 100871, Peoples R China; [Zhu, Wei-Guo] Peking Univ Tsinghua Univ Ctr Life Sci, Beijing, Peoples R China; [Zhu, Wei-Guo] Shenzhen Univ, Sch Med, Shenzhen, Peoples R China		Zhu, WG (corresponding author), Peking Univ, Beijing Key Lab Prot Posttranslat Modificat & Cel, Dept Biochem & Mol Biol,Hlth Sci Ctr,Minist Educ, State Key Lab Nat & Biomimet Drugs,Key Lab Carcin, Beijing 100871, Peoples R China.	zhaoying0812@bjmu.edu.cn; zhuweiguo@bjmu.edu.cn	Ushijima, Toshikazu/AAP-5742-2021; Du, Yipeng/O-1223-2013	Ushijima, Toshikazu/0000-0003-3405-7817; Zhu, Wei-Guo/0000-0001-8385-6581; Yang, Yang/0000-0002-8737-590X; Hattori, Naoko/0000-0002-0901-4869; Wang, Haiying/0000-0001-7729-0649	973 ProjectsNational Basic Research Program of China [2011CB910100, 2011CB504200, 2013CB911000]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81222028, 81321003, 81472581, 81530074, 31570812, 91319302]; Ministry of Science and Technology of ChinaMinistry of Science and Technology, China [B70001]	This study was supported by the "973 Projects" (2011CB910100, 2011CB504200 and 2013CB911000); National Natural Science Foundation of China (81222028, 81321003, 81472581, 81530074, 31570812 and 91319302), and grants (B70001) from the Ministry of Science and Technology of China.	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J	Li, H; Chen, C				Li, Hai; Chen, Chen			Inhibition of autophagy enhances synergistic effects of Salidroside and anti-tumor agents against colorectal cancer	BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE			English	Article						Salidroside; Autophagy; AMPK signaling; Anti-tumor agents; Colorectal cancer	IN-VITRO; CELLS; JAK2/STAT3; APOPTOSIS; GROWTH	Background: Various plant extracts have been suggested to be used as auxiliary agents in chemotherapy considering their anti-proliferative effect on cancer cells. However, recent reports reveal that plant extracts may function as inducers of autophagy of cancer cells. In general, autophagy confers survival advantage for cells responding to stress conditions, thus representing an important mechanism for chemo-resistance. This study was aimed to investigate the effectiveness of combined use of Salidroside (Sal, a phenylpropanoid glycosides from Rhodiola rosea L) with anti-tumor agents against colorectal cancer (CRC) cells, and moreover to evaluate the potential role of autophagy in the combined therapy. Methods: CRC cells, HCT-116, were incubated with Sal alone or in combination with conventional chemotherapy agents including oxaliplatin (OXA), 5-fluorouracil (5-FU) and Doxorubicin (ADM). Cell proliferative characteristics were evaluated by cell viability and apoptosis rate. The protein expression was assessed by Immunofluorescent and Western blot assays. Results: Sal, alone or in combination with anti-tumor agents, increased expression of autophagic biomarkers, including LC3B and Becline-1, suggesting an autophagy induction. Except for the up-regulation of p-AMPK, p-mTOR, p-NF-kappa B (p65), TGF-beta, p-JAK2 and p-STAT3 were down-regulated by Sal. Because autophagy is positively correlated with the activation of AMPK/mTOR, NF-kappa B, TGF beta 1 and JAK2/STAT3 cascades, the autophagy induced by Sal may associate with AMPK activation. Indeed, blockage of AMPK signaling via Compound C or AMPK knockdown inhibited the autophagy. The blockage of AMPK signaling or a direct inhibition of autophagy via 3-MA increased effectiveness of combined use of Sal with anti-tumor agents against CRC. Conclusions: Inhibition of autophagy enhances synergistic effects of Sal and anti-tumor agents against colorectal cancer. This study provides experimental evidence and theoretical reference for improvement of a novel chemotherapy treatment protocol.	[Li, Hai] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Geriatr, Tongji Med Coll, Wuhan, Hubei, Peoples R China; [Chen, Chen] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Breast & Thyroid Surg, Union Hosp, Wuhan, Hubei, Peoples R China		Li, H (corresponding author), Huazhong Univ Sci & Technol, Tongji Hosp, Dept Geriatr, Tongji Med Coll, Wuhan, Hubei, Peoples R China.	lihaiges@hust.edu.cn		Li, Hai/0000-0001-7937-5902	Shenzhen Municipal Commission of science and technology innovation [JCYJ20150402152005631]	This study was supported by the Shenzhen Municipal Commission of science and technology innovation (Grant No. JCYJ20150402152005631).	Bastola T, 2017, MOLECULES, V22, DOI 10.3390/molecules22020242; Chan SH, 2012, J BIOMED SCI, V19, DOI 10.1186/1423-0127-19-64; Chen WTL, 2014, NUTR RES, V34, P585, DOI 10.1016/j.nutres.2014.06.010; Cho YS, 2016, SCI REP-UK, V6, DOI 10.1038/srep34655; Einbond LS, 2017, PHYTOMEDICINE, V24, P1, DOI 10.1016/j.phymed.2016.11.002; Hao MJ, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18030614; Huang WW, 2017, KAOHSIUNG J MED SCI, V33, P308, DOI 10.1016/j.kjms.2017.03.004; Jang JE, 2017, AUTOPHAGY, V13, P761, DOI 10.1080/15548627.2016.1278328; Kim KY, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18051088; Law BYK, 2016, MOLECULES, V21, DOI 10.3390/molecules21030359; Liu ZY, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0177694; Lv C, 2016, CANCER BIOMARK, V17, P41, DOI 10.3233/CBM-160615; Ma YG, 2017, BMC PHARMACOL TOXICO, V18, DOI 10.1186/s40360-017-0135-8; Pratt J, 2014, CELL SIGNAL, V26, P917, DOI 10.1016/j.cellsig.2014.01.012; Rong LW, 2017, ONCOL LETT, V13, P5028, DOI 10.3892/ol.2017.6059; Shen J, 2017, EUR REV MED PHARMACO, V21, P1013; Sonowal H, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-03284-w; Wang J, 2014, ONCOL LETT, V7, P1159, DOI 10.3892/ol.2014.1863; Xie J, 2016, BMC CANCER, V16, DOI 10.1186/s12885-016-2921-x; Xu Z, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18030524; Zhao G, 2015, ONCOL REP, V33, P2553, DOI 10.3892/or.2015.3857; Zhou DZ, 2017, FREE RADICAL RES, V51, P517, DOI 10.1080/10715762.2017.1328552; Zhu Q, 2017, NEOPLASMA, V64, P709, DOI 10.4149/neo_2017_508	23	30	36	0	15	BIOMED CENTRAL LTD	LONDON	236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND	1472-6882			BMC COMPLEM ALTERN M	BMC Complement. Altern. Med.	DEC 16	2017	17								538	10.1186/s12906-017-2046-z			9	Integrative & Complementary Medicine	Science Citation Index Expanded (SCI-EXPANDED)	Integrative & Complementary Medicine	FQ0XD	WOS:000418079400002	29246220	Green Published, gold			2022-04-25	
J	Gutierrez-Martinez, IZ; Rubio, JF; Piedra-Quintero, ZL; Lopez-Mendez, O; Serrano, C; Reyes-Maldonado, E; Salinas-Lara, C; Betanzos, A; Shibayama, M; Silva-Olivares, A; Candelario-Martinez, A; Meraz-Rios, MA; Schnoor, M; Villegas-Sepulveda, N; Nava, P				Gutierrez-Martinez, I. Z.; Rubio, J. F.; Piedra-Quintero, Z. L.; Lopez-Mendez, O.; Serrano, C.; Reyes-Maldonado, E.; Salinas-Lara, C.; Betanzos, A.; Shibayama, M.; Silva-Olivares, A.; Candelario-Martinez, A.; Meraz-Rios, M. A.; Schnoor, M.; Villegas-Sepulveda, N.; Nava, P.			mTORC1 Prevents Epithelial Damage During Inflammation and Inhibits Colitis-Associated Colorectal Cancer Development	TRANSLATIONAL ONCOLOGY			English	Article							DNA-DAMAGE; COLONIC EPITHELIUM; MAMMALIAN TARGET; KINASE INHIBITOR; E-CADHERIN; LITHIUM; AUTOPHAGY; CELLS; DOXORUBICIN; INTESTINE	Epithelial cells lining the intestinal mucosa constitute a selective-semipermeable barrier acting as first line of defense in the organism. The number of those cells remains constant during physiological conditions, but disruption of epithelial cell homeostasis has been observed in several pathologies. During colitis, epithelial cell proliferation decreases and cell death augments. The mechanism responsible for these changes remains unknown. Here, we show that the pro-inflammatory cytokine IFN gamma contributes to the inhibition of epithelial cell proliferation in intestinal epithelial cells (IECs) by inducing the activation of mTORC1. Activation of mTORC1 in response to IFN gamma was detected in IECs present along the crypt axis and in colonic macrophages. mTORC1 inhibition enhances cell proliferation, increases DNA damage in IEC. In macrophages, mTORC1 inhibition strongly reduces the expression of pro-inflammatory markers. As a consequence, mTORC1 inhibition exacerbated disease activity, increased mucosal damage, enhanced ulceration, augmented cell infiltration, decreased survival and stimulated tumor formation in a model of colorectal cancer CRC associated to colitis. Thus, our findings suggest that mTORC1 signaling downstream of IFN gamma prevents epithelial DNA damage and cancer development during colitis.	[Gutierrez-Martinez, I. Z.; Rubio, J. F.; Lopez-Mendez, O.; Serrano, C.; Candelario-Martinez, A.; Nava, P.] CINVESTAV, Dept Physiol Biophys & Neurosci, Mexico City 07360, DF, Mexico; [Piedra-Quintero, Z. L.; Meraz-Rios, M. A.; Schnoor, M.; Villegas-Sepulveda, N.] CINVESTAV, Dept Mol Biomed, Mexico City 07360, DF, Mexico; [Reyes-Maldonado, E.] Natl Polytech, Natl Sch Biol Sci, Dept Morphol, Mexico City 11340, DF, Mexico; [Salinas-Lara, C.] UNAM, FES Iztacala, Surg & Med Sch, Histol & Pathol Unit, Tlalnepantla 54090, Mexico; [Betanzos, A.; Shibayama, M.; Silva-Olivares, A.] CINVESTAV, Dept Infect & Mol Pathogenesis, Mexico City 07360, DF, Mexico		Serrano, C; Nava, P (corresponding author), Cinvestav Zacatenco, Dept Physiol Biophys & Neurosci, Av Inst Politecn Nacl 2508, Mexico City 07360, DF, Mexico.	serrano.cisg@gmail.com; pnava@fisio.cinvestav.mx	Meraz-Rios, Marco Antonio/F-4194-2016; Nava, Porfirio/D-8306-2012; SALINAS, CITLALTEPETL/AAG-4810-2020; Schnoor, Michael/H-1863-2016	Meraz-Rios, Marco Antonio/0000-0001-6748-8117; Nava, Porfirio/0000-0002-0506-1510; Schnoor, Michael/0000-0002-0269-5884; Villegas-Sepulveda, Nicolas/0000-0001-9489-2545	Premio Lisker 2016	This work was supported by the Premio Lisker 2016 (PND). We thank Norma Trejo for their excellent technical assistance.	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Oncol.	JAN	2019	12	1					24	35		10.1016/j.tranon.2018.08.016			12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	HD9OU	WOS:000452892800004	30265974	gold, Green Published			2022-04-25	
J	Hao, HB; Xia, GF; Wang, C; Zhong, FP; Liu, LP; Zhang, D				Hao, Haibin; Xia, Guangfeng; Wang, Chao; Zhong, Fuping; Liu, Laipeng; Zhang, Dong			miR-106a suppresses tumor cells death in colorectal cancer through targeting ATG7	MEDICAL MOLECULAR MORPHOLOGY			English	Article						Colorectal cancer; miR-106a; ATG7; Cell death	GASTRIC-CANCER; AUTOPHAGY; EXPRESSION; PROLIFERATION; METASTASIS; RESISTANCE; APOPTOSIS; PATHWAY; BREAST	Autophagy-related gene 7 (ATG7) and miR-106a play an important role in cancer cell autophagy and apoptosis, but the outcome of ATG7 and miR-106a in colorectal cancer (CRC) still remains not clear. In this study, we found that ATG7 and miR-106a expression were mutually related with cell death and prognosis in CRC patients. In addition, we also showed that ATG7 and miR-106a expression were changeable in colorectal cancer cell lines when compared with normal cell lines, but ATG7 and miR-106a mRNA level was negatively correlated. Furthermore, ATG7 protein and mRNA levels decreased after over-expression of miR-106a, whereas the suppression of ATG7 had the opposite effect. We confirmed that miR-106a down-regulated ATG7 mRNA level by binding the specific sequence of ATG7 mRNA 3'UTR region. Moreover, the over-expression of ATG7 induced CRC cells death both in vitro and in vivo. Taken together, our study data demonstrated that ATG7 aggravated the cell death of CRC, which was inhibited by miR-106a.	[Hao, Haibin; Xia, Guangfeng; Wang, Chao; Zhong, Fuping; Liu, Laipeng; Zhang, Dong] Nanchang Univ, Affiliated Hosp 2, Dept Gen Surg, Med Coll, 461 Bayi Rd, Nanchang 330006, Jiangxi, Peoples R China		Hao, HB (corresponding author), Nanchang Univ, Affiliated Hosp 2, Dept Gen Surg, Med Coll, 461 Bayi Rd, Nanchang 330006, Jiangxi, Peoples R China.	haoweipei104@163.com					Arnold M, 2016, GUT; Baquero P, 2015, BR J HAEMATOL, V6; Bovell LC, 2013, CLIN CANCER RES, V19, P3955, DOI 10.1158/1078-0432.CCR-12-3302; Brody H, 2015, NATURE, V521, pS1, DOI 10.1038/521S1a; Chang TK, 2013, NAT CELL BIOL, V15, P1067, DOI 10.1038/ncb2804; Chen WY, 2015, INT J CLIN EXP PATHO, V8, P7092; Comincini S, 2013, CANCER BIOL THER, V14, P574, DOI 10.4161/cbt.24597; Ergun M, 2013, EUR J CANCER CARE, V22, P626, DOI 10.1111/ecc.12068; Gomez-Puerto MC, 2016, STEM CELLS; Hao H, 2016, ONCOTARGET, DOI 10.18632/oncotarget.13766; Hofius D, 2009, CELL, V137, P773, DOI 10.1016/j.cell.2009.02.036; Hsieh YY, 2016, AM J CANCER RES, V6, P1661; Ivkovic TC, 2013, EXP MOL PATHOL, V94, P148, DOI 10.1016/j.yexmp.2012.11.002; Komatsu M, 2005, J CELL BIOL, V169, P425, DOI 10.1083/jcb.200412022; Ma HL, 2015, CELL MOL BIOL, V61, P56; Masui A, 2016, PLOS ONE, V11, DOI 10.1371/journal.pone.0162786; McCoy F, 2010, CELL DEATH DIS, V1, DOI 10.1038/cddis.2010.86; Moscat J, 2009, CELL, V137, P1001, DOI 10.1016/j.cell.2009.05.023; Qi LQ, 2009, BMC CANCER, V9, DOI 10.1186/1471-2407-9-163; Qiu YM, 2015, BIOCHEM BIOPH RES CO, V467, P629, DOI 10.1016/j.bbrc.2015.10.103; Wang R, 2015, ONCOTARGET, V6, P7000, DOI 10.18632/oncotarget.3193; Wang ZZ, 2013, MOL CARCINOGEN, V52, P634, DOI 10.1002/mc.21899; Yang G, 2011, J MOL MED, V89, P1037, DOI 10.1007/s00109-011-0775-x; Yu L, 2004, SCIENCE, V304, P1500, DOI 10.1126/science.1096645; Yuan RS, 2015, TUMOR BIOL, V36, P3093, DOI 10.1007/s13277-014-2945-2; Zeng YC, 2015, J MOL NEUROSCI, V56, P815, DOI 10.1007/s12031-015-0514-9; Zhang Y, 2013, FEBS LETT, V587, P3069, DOI 10.1016/j.febslet.2013.06.058; Zhu M, 2016, CLIN EXP METASTAS, V33, P509, DOI 10.1007/s10585-016-9795-9	28	25	27	0	8	SPRINGER JAPAN KK	TOKYO	SHIROYAMA TRUST TOWER 5F, 4-3-1 TORANOMON, MINATO-KU, TOKYO, 105-6005, JAPAN	1860-1480	1860-1499		MED MOL MORPHOL	Med. Mol. Morphol.	JUN	2017	50	2					76	85		10.1007/s00795-016-0150-7			10	Biology; Microscopy; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Life Sciences & Biomedicine - Other Topics; Microscopy; Pathology	EV5FW	WOS:000401788900003	27981410				2022-04-25	
J	Jang, JH; Baerts, L; Waumans, Y; De Meester, I; Yamada, Y; Limani, P; Gil-Bazo, I; Weder, W; Jungraithmayr, W				Jang, Jae-Hwi; Baerts, Lesley; Waumans, Yannick; De Meester, Ingrid; Yamada, Yoshito; Limani, Perparim; Gil-Bazo, Ignacio; Weder, Walter; Jungraithmayr, Wolfgang			Suppression of lung metastases by the CD26/DPP4 inhibitor Vildagliptin in mice	CLINICAL & EXPERIMENTAL METASTASIS			English	Article						CD26/DPP4; Lung metastases; Autophagy; Apoptosis	DIPEPTIDYL-PEPTIDASE-IV; ANTI-CD26 MONOCLONAL-ANTIBODY; IN-VITRO; COLORECTAL-CANCER; CD26 EXPRESSION; TUMOR-GROWTH; STEM-CELLS; AUTOPHAGY; VIVO; LOCALIZATION	Metastases rather than primary cancers determine nowadays the survival of patients. One of the most common primary malignancies is colorectal cancer and this type of tumor is characterized by a high tendency to spread metastases to the lung and liver. CD26/DPP4 is a transmembrane molecule with enzymatic functions which cleaves biologically active peptides. Recently, CD26/DPP4 has become the focus of cancer research and it was shown that CD26/DPP4-positive cancer cells display increased metastatic activity. Here, we tested if the CD26/DPP4-inhibitor Vildagliptin suppresses the development and growth of mouse colorectal lung metastases. This inhibitor of CD26/DPP4 was employed on mouse (C57BL/6) colorectal lung metastases, established by intravenous injection of the syngeneic cell line MC38. For mechanistic analysis, a subcutaneous tumor model was used. The treatment with Vildagliptin significantly suppressed both, the incidence and growth of lung metastases. Autophagy markers (LC3, p62, and ATF4) decreased, apoptosis increased (TUNEL, pH3/Ki-76), and the cell cycle regulator pCDC2 was inhibited. In conclusion, we here showed an anti-tumor effect of Vildagliptin via downregulation of autophagy resulting in increased apoptosis and modulation of the cell cycle. We therefore propose Vildagliptin for the evaluation as a new therapeutic approach for the treatment of colorectal cancer lung metastases.	[Jang, Jae-Hwi; Yamada, Yoshito; Weder, Walter; Jungraithmayr, Wolfgang] Univ Zurich Hosp, Div Thorac Surg, CH-8091 Zurich, Switzerland; [Baerts, Lesley; Waumans, Yannick; De Meester, Ingrid] Univ Antwerp, Dept Pharmaceut Sci, Dept Med Biochem, B-2020 Antwerp, Belgium; [Limani, Perparim] Univ Zurich Hosp, Dept Visceral & Transplantat Surg, CH-8091 Zurich, Switzerland; [Gil-Bazo, Ignacio] Univ Navarra, Ctr Appl Med Res, Div Oncol, E-31080 Pamplona, Spain		Jungraithmayr, W (corresponding author), Univ Zurich Hosp, Div Thorac Surg, Raemistr 100, CH-8091 Zurich, Switzerland.	wolfgang.jungraithmayr@usz.ch	Jungraithmayr, Wolfgang/F-3882-2015; De Meester, Ingrid/A-6881-2017; Gil-Bazo, Ignacio/E-4581-2019	Jungraithmayr, Wolfgang/0000-0002-1442-4862; De Meester, Ingrid/0000-0002-3421-0124; Gil-Bazo, Ignacio/0000-0002-2626-5109	Swiss National Science Foundation (SNF)Swiss National Science Foundation (SNSF) [310030 156876/1]; Stiftung fur wissenschaftliche Forschung'; University of Antwerp [FFB3551]	We thank Dr. Lubor Borsig and Dr. Radovan Borojevic for kindly providing the MC38 (GFP) and GRX cell lines. This study is supported by Swiss National Science Foundation (SNF, 2014, 310030 156876/1) and the 'Stiftung fur wissenschaftliche Forschung' 2015 to WJ and by a special research fund of the University of Antwerp (FFB3551).	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Exp. Metastasis	OCT	2015	32	7					677	687		10.1007/s10585-015-9736-z			11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CR9ZF	WOS:000361715300004	26233333	Green Published, Green Accepted			2022-04-25	
J	Grasso, S; Pereira, GJS; Palmeira-dos-Santos, C; Calgarotto, AK; Martinez-Lacaci, I; Ferragut, JA; Smaili, SS; Bincoletto, C				Grasso, Silvina; Pereira, Gustavo J. S.; Palmeira-dos-Santos, Caroline; Calgarotto, Andrana K.; Martinez-Lacaci, Isabel; Antonio Ferragut, Jose; Smaili, Soraya S.; Bincoletto, Claudia			Autophagy regulates Selumetinib (AZD6244) induced-apoptosis in colorectal cancer cells	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY			English	Article						Apoptosis; Autophagy; Selumetinib (AZD6244); CRC cells (SW480 and HT29)	INHIBITOR SELUMETINIB; DRUG-RESISTANCE; OPEN-LABEL; PHASE-II; ARRY-142886; PROTEIN; THERAPY; PATHWAYS; TRIAL; MELANOMA	Objective: As Selumetinib is a MEK1/2 inhibitor that has gained interest as an anti-tumor agent, the present study was designed to investigate autophagy involvement on Selumetinib-induced apoptosis in colorectal cancer (CRC) cells. Methods: CRC cells death and cycle studies were assessed by AnnexinV-FITC and PI staining, respectively. Autophagy flux was analysed by Western Blot (LC3II and p62 protein levels) and retroviral infection of SW480 cells for siBecn1 RNA interference experiments. Confocal microscopy was used to determine mCherry-EGFP-LC3 distribution. Key findings: The Selumetinib effects were concentration-dependent in SW480 cell line. Whereas 1 mu M exerted an arrest in the cell cycle (G1 phase), higher concentrations (10 mu M) induced cell death, which was accompanied by autophagy blockage in its last stages. Autophagy induction by Rapamycin (RAPA) increased cell survival, whereas pharmacology autophagy inhibition by Bafilomycin A1 (BAF), Chloroquine (CQ) or 3-Methyladenine (3-MA) increased Selumetinib-induced CRC cells death. Conclusions: Altogether, these results suggest that autophagy plays a fundamental role in CRC cells response to Selumetinib. In addition, the combination of Selumetinib with autophagy inhibitors may be a useful therapeutic strategy to enhance its activity against colorectal tumours. (C) 2016 Elsevier Masson SAS. All rights reserved.	[Grasso, Silvina; Martinez-Lacaci, Isabel; Antonio Ferragut, Jose] Univ Miguel Hernandez, Inst Biol Mol & Celular, Alicante 03202, Spain; [Grasso, Silvina; Pereira, Gustavo J. S.; Palmeira-dos-Santos, Caroline; Calgarotto, Andrana K.; Smaili, Soraya S.; Bincoletto, Claudia] Univ Fed Sao Paulo UNIFESP, Escola Paulista Med, Dept Farmacol, Rua Tres Maio 100, Sao Paulo, SP, Brazil; [Martinez-Lacaci, Isabel] Hosp Univ Virgen de la Arrixaca, Unidad AECC Invest Traslac Canc, Inst Murciano Invest Biosanitaria, Murcia 30120, Spain		Smaili, SS; Bincoletto, C (corresponding author), Univ Fed Sao Paulo UNIFESP, Escola Paulista Med, Dept Farmacol, Rua Tres Maio 100, Sao Paulo, SP, Brazil.	soraya.smaili23@gmail.com; claudia.bincoletto@unifesp.br	Bincoletto, Claudia/H-4936-2012; Pereira, Gustavo José Silva/ABH-1344-2020; Smaili, Soraya/AAH-2129-2019; Pereira, Gustavo/H-4636-2012	Pereira, Gustavo/0000-0002-6765-1276	FAPESPFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [12/51215-4]; CAPESCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); CNPqConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ)	This work was supported by research grants from FAPESP (12/51215-4), CAPES and CNPq. The authors thank Dr. Hanako Hirata, Cicero Santos and Bruno Palmieri de Souza for excellent technical assistance.	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J. Med. Chem.	OCT 21	2016	122						611	618		10.1016/j.ejmech.2016.06.043			8	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	DV5XL	WOS:000383003900052	27448918				2022-04-25	
J	Byun, HO; Han, NK; Lee, HJ; Kim, KB; Ko, YG; Yoon, G; Lee, YS; Hong, SI; Lee, JS				Byun, Hae-Ok; Han, Na-Kyung; Lee, Hae-June; Kim, Ki-Bum; Ko, Young-Gyu; Yoon, Gyesoon; Lee, Yun-Sil; Hong, Seok-Il; Lee, Jae-Seon			Cathepsin D and Eukaryotic Translation Elongation Factor 1 as Promising Markers of Cellular Senescence	CANCER RESEARCH			English	Article							ACCELERATED SENESCENCE; IN-VIVO; TUMOR-REGRESSION; CANCER CELLS; APOPTOSIS; P53; EXPRESSION; RADIATION; ARREST; DEATH	Induction of premature senescence may be a promising strategy for cancer treatment. However, biomarkers for senescent cancer cells are lacking. To identify such biomarkers, we performed comparative proteomic analysis of MCF7 human breast cancer cells undergoing cellular senescence in response to ionizing radiation (IR). IR-induced senescence was associated with up-regulation of cathepsin D (CD) and down-regulation of eukaryotic translation elongation factor 1 beta 2 (eEF1B2), as confirmed by Western blot. The other elongation factor, eukaryotic translation elongation factor 1 alpha 1 (eEF1A1), was also down-regulated. IR-induced senescence was associated with similar changes of CD and eEF1 (eEF1A1 and eEF1B2) levels in the HCT116 colon cancer cell line and the H460 lung cancer cell line. Up-regulation of CD and down-regulation of eEF1 seemed to be specific to senescence, as they were observed during cellular senescence induced by hydrogen peroxide or anticancer drugs (camptothecin, etoposide, or 50 ng doxorubicin) but not during apoptosis induced by Taxol or 10 mu g doxorubicin or autophagy induced by tamoxifen. The same alterations in CD and eEF1A1 levels were observed during replicative senescence and Ras oncogene-induced senescence. Transient cell cycle arrest did not alter levels of eEF1 or CD. Chemical inhibition of CD (pepstatin A) and small interfering RNA-mediated knockdown of CD and eEF1 revealed that these factors participate in cell proliferation. Finally, the senescence-associated alteration in CD and eEF1 levels observed in cell lines was also observed in IR-exposed xenografted tumors. These findings show that CD and eEF1 are promising markers for the detection of cellular senescence induced by a variety of treatments. [Cancer Res 2009;69(11):4638-47]	[Byun, Hae-Ok; Han, Na-Kyung; Lee, Jae-Seon] Korea Inst Radiol & Med Sci, Div Radiat Canc Res, Seoul 139706, South Korea; [Lee, Hae-June; Lee, Yun-Sil] Korea Inst Radiol & Med Sci, Div Radiat Effects, Seoul 139706, South Korea; [Hong, Seok-Il] Korea Inst Radiol & Med Sci, Dept Lab Med & Clin Pathol, Seoul 139706, South Korea; [Han, Na-Kyung; Kim, Ki-Bum; Ko, Young-Gyu] Korea Univ, Grad Sch Life Sci & Biotechnol, Seoul, South Korea; [Yoon, Gyesoon] Ajou Univ, Sch Med, Dept Biochem, Suwon 441749, South Korea; [Yoon, Gyesoon] Ajou Univ, Grad Sch, Dept Mol Sci & Technol, Suwon 441749, South Korea		Lee, JS (corresponding author), Korea Inst Radiol & Med Sci, Div Radiat Canc Res, Seoul 139706, South Korea.	jaeslee@kcch.re.kr	Lee, Yun-Sil/AAP-1378-2020	Lee, Yun-Sil/0000-0002-7538-8850	Ministry of Education, Science, and Technology of KoreaMinistry of Education, Science and Technology, Republic of Korea	National Nuclear Technology Program from The Ministry of Education, Science, and Technology of Korea.	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JUN 1	2009	69	11					4638	4647		10.1158/0008-5472.CAN-08-4042			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	455JL	WOS:000266755000014	19487283	Green Published			2022-04-25	
J	Mi, WN; Wang, CY; Luo, G; Li, JH; Zhang, YZ; Jiang, MM; Zhang, CC; Liu, NN; Jiang, XX; Yang, G; Zhang, LL; Zhang, G; Zhang, YJ; Fu, Y				Mi, Wunan; Wang, Chuyue; Luo, Guang; Li, Jiehan; Zhang, Yizheng; Jiang, Meimei; Zhang, Chuchu; Liu, Nannan; Jiang, Xinxiu; Yang, Ge; Zhang, Lingling; Zhang, Ge; Zhang, Yingjie; Fu, Yang			Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer	CELL DEATH DISCOVERY			English	Article							WILD-TYPE; APOPTOSIS; P53; ROS; STATISTICS	In recent years, many studies have shown that autophagy plays a vital role in the resistance of tumor chemotherapy. However, the interaction between autophagy and cell death has not yet been clarified. In this study, a new specific ERK inhibitor CC90003 was found to suppress colorectal cancer growth by inducing cell death both in vitro and in vivo. Studies have confirmed that higher concentrations of ROS leads to autophagy or cell death. In this research, the role of CC90003-induced ROS was verified. But after inhibiting ROS by two kinds of ROS inhibitors NAC and SFN, the autophagy induced by CC90003 decreased, while cell death strengthened. In parallel, protective autophagy was also induced, while in a p53-dependent manner. After silencing p53 or using the p53 inhibitor PFT alpha, the autophagy induced by CC90003 was weakened and the rate of cell death increases. Therefore, we confirmed that CC90003 could induce autophagy by activating ROS/p53. Furthermore, in the xenograft mouse model, the effect was obtained remarkably in the combinational treatment group of CC90003 plus CQ, comparing with that of the single treatment groups. In a word, our results demonstrated that targeting ERK leads to cell death and p53/ROS-dependent protective autophagy simultaneously in colorectal cancer, which offers new potential targets for clinical therapy.	[Mi, Wunan; Li, Jiehan; Zhang, Yizheng; Zhang, Ge; Fu, Yang] Zhengzhou Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Zhengzhou 450052, Peoples R China; [Mi, Wunan; Wang, Chuyue; Zhang, Yizheng; Jiang, Meimei; Zhang, Chuchu; Liu, Nannan; Jiang, Xinxiu; Zhang, Yingjie] Hunan Univ, Coll Biol, Changsha 410082, Peoples R China; [Mi, Wunan; Zhang, Yingjie] Hunan Univ, Sch Biomed Sci, Changsha 410082, Peoples R China; [Luo, Guang; Zhang, Lingling] Cent South Univ, Xiangya Hosp 3, Dept Lab Med, Changsha 410013, Peoples R China; [Yang, Ge] Zhengzhou Univ, Affiliated Hosp 1, Dept Ophthalmol, Zhengzhou 450052, Peoples R China; [Fu, Yang] Collaborat Innovat Ctr Henan Prov Canc Chemopreve, Zhengzhou 450052, Peoples R China		Fu, Y (corresponding author), Zhengzhou Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Zhengzhou 450052, Peoples R China.; Zhang, YJ (corresponding author), Hunan Univ, Coll Biol, Changsha 410082, Peoples R China.; Zhang, YJ (corresponding author), Hunan Univ, Sch Biomed Sci, Changsha 410082, Peoples R China.; Fu, Y (corresponding author), Collaborat Innovat Ctr Henan Prov Canc Chemopreve, Zhengzhou 450052, Peoples R China.	yingjiezhang@hnu.edu.cn; fuyang@zzu.edu.cn			Chinese National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81871995, 31801140, 31701132]; Project of Henan Health Department [YXKC2020029/2020054, SBGJ201901049/2020002041]; Excellent Youth Fund of Henan Natural Science Foundation [212300410075]; Natural Science Foundation of Hunan ProvinceNatural Science Foundation of Hunan Province [2020JJ4182, 2019JJ40366]; province-ministry joint construction project of Henan Provincial Health Commission [SB201901049]	This study was supported by Chinese National Natural Science Foundation (Nos. 81871995, 31801140, and 31701132), the Project of Henan Health Department (Nos. YXKC2020029/2020054 and SBGJ201901049/2020002041), the Excellent Youth Fund of Henan Natural Science Foundation (No. 212300410075), the Natural Science Foundation of Hunan Province (2020JJ4182 and 2019JJ40366), and province-ministry joint construction project of Henan Provincial Health Commission (SB201901049).	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DEC 4	2021	7	1							375	10.1038/s41420-021-00677-9			11	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	XI7LP	WOS:000726288400001	34864826	Green Published, gold			2022-04-25	
J	Lu, WY; Lin, CH; Li, YH				Lu, Wenyan; Lin, Cuihong; Li, Yonghe			Rottlerin induces Wnt co-receptor LRP6 degradation and suppresses both Wnt/beta-catenin and mTORC1 signaling in prostate and breast cancer Cells	CELLULAR SIGNALLING			English	Article						LRP6; Wnt signaling; mTORCI signaling; Rottlerin; Cancer; Drug discovery	DELTA-INDEPENDENT PATHWAY; COLON-CARCINOMA CELLS; CYCLIN D1 EXPRESSION; INDUCED APOPTOSIS; UP-REGULATION; BETA-CATENIN; AUTOPHAGY; INHIBITION; SURVIVIN; TARGET	Activation of Wnt/beta-catenin signaling can result in up-regulation of mTORC1 signaling in cancer cells. The low density lipoprotein receptor-related protein-6 (LRP6) is an essential Wnt co-receptor for Wnt/S-catenin signaling. We found that rottlerin, a natural plant polyphenol, suppressed LRP6 expression and phosphotylation, and inhibited Wnt43-catenin signaling in HEK293 cells. Furthermore, the inhibitory effects of rottlerin on LRP6 expression/phosphorylation and Wnt/beta-catenin signaling were confirmed in human prostate cancer PC-3 and DU145 cells and breast cancer MDA-MB-231 and T-47D cells. Mechanistically, rottlerin promoted LRP6 degradation, but had no effects on LRP6 transcriptional activity. In addition, rottlerin-mediated LRP6 downregulation was unrelated to activation of 5'-AMP-activated protein kinase (AMPK). Importantly, we also found that rottlerin inhibited mTORC1 signaling in prostate and breast cancer cells. Finally, we demonstrated that rottlerin was able to suppress the expression of cyclin D1 and survivin, two targets of both Wnt/S-catenin and mTORC1 signaling, in prostate and breast cancer cells, and displayed remarkable anticancer activity with IC50 values between 0.7 and 1.7 mu M for prostate cancer PC-3 and DU145 cells and breast cancer MDA-MB-231 and T-47D cells. The IC50 values are comparable to those shown to suppress the activities of Wnt/S-catenin and mTORC1 signaling in prostate and breast cancer cells. Our data indicate that rottlerin is a novel LRP6 inhibitor and suppresses both Wnt/S-catenin and mTORC1 signaling in prostate and breast cancer cells, and that LRP6 represents a potential therapeutic target for cancers. (c) 2014 Elsevier B.V. All rights reserved.	[Lu, Wenyan; Lin, Cuihong; Li, Yonghe] So Res Inst, Dept Biochem & Mol Biol, Drug Discovery Div, Birmingham, AL 35205 USA; [Lin, Cuihong] Fujian Med Univ, Affiliated Hosp 1, Dept Pharm, Fuzhou, Peoples R China		Li, YH (corresponding author), So Res Inst, Dept Biochem & Mol Biol, Drug Discovery Div, 2000 Ninth Ave South, Birmingham, AL 35205 USA.	y.li@souternresearch.org			National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01CAl24531, R21CA182056]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA124531, R21CA182056] Funding Source: NIH RePORTER	We are grateful to Dr. Christof Niehrs (Deutsches Krebsforschungszentrum, Heidelberg, Germany) for providing LRP6 cDNA, Dr. Gail Johnson (University of Rochester) for providing GST-E Cadherin cDNA, and Dr. Randall T. Moon (University of Washington) for providing the Super8XTOPFlash luciferase construct. This work was supported by grants from the National Institutes of Health R01CAl24531 and R21CA182056 (to Y.L.).	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Signal.	JUN	2014	26	6					1303	1309		10.1016/j.cellsig.2014.02.018			7	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	AG0OH	WOS:000335114300015	24607787	Green Accepted			2022-04-25	
J	Neilsen, BK; Kelly, DL; Chakraborty, B; Kim, HS; White, MA; Lewis, RE; Fisher, KW				Neilsen, Beth K.; Kelly, David L.; Chakraborty, Binita; Kim, Hyun Seok; White, Michael A.; Lewis, Robert E.; Fisher, Kurt W.			High-throughput identification of protein functional similarities using a gene-expression-based siRNA screen	SCIENTIFIC DATA			English	Article; Data Paper								A gene expression-based siRNA screen was used to evaluate functional similarity between genetic perturbations to identify functionally similar proteins. A siRNA library (siGenome library, Dharmacon) consisting of multiple siRNAs per gene that have been pooled in to one well per gene was arrayed in a 384-well format and used to individually target 14,335 proteins for depletion in HCT116 colon cancer cells. For each protein depletion, the gene expression of eight genes was quantified using the multiplexed Affymetrix Quantigene 2.0 assay in technical triplicate. As a proof of concept, six genes (BNIP3, NDRG1, ALDOC, LOXL2, ACSL5, BNIP3L) whose expression pattern reliably reflect the disruption of the molecular scaffold KSR1 were measured upon each protein depletion. The remaining two genes (PPIB and HPRT) are housekeeping genes used for normalization. The gene expression signatures from this screen can be used to estimate the functional similarity between any two proteins and successfully identified functional relationships for specific proteins such as KSR1 and more generalized processes, such as autophagy.	[Neilsen, Beth K.; Kelly, David L.; Lewis, Robert E.] Univ Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Eppley Inst, Omaha, NE 68198 USA; [Chakraborty, Binita] Duke Univ, Med Ctr, Pharmacol & Canc Biol, Durham, NC 27710 USA; [Kim, Hyun Seok] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul, South Korea; [White, Michael A.] Univ Texas Southwestern Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA; [Fisher, Kurt W.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA		Fisher, KW (corresponding author), Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA.	kfisher@unmc.edu		Fisher, Kurt/0000-0002-8391-390X; Neilsen, Beth/0000-0002-4859-6486	NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA157774, GM121316, CA203397, CA22287]; Eppley Institute in Cancer Biology training grant [NCI T32CA009476]; NPOD COBRE [NIH P20 GM104320]; Fred & Pamela Buffett Cancer Center Support Grant [P30 CA036727]	We thank Amy Wells from the University of Nebraska Medical Center (UNMC) Eppley Institute high-throughput screening facility for her assistance. This work was supported by grants from NCI (CA157774 and GM121316 to R.E.L.; CA203397 to B.K.N., and CA22287 to K.W.F), Eppley Institute in Cancer Biology training grant (NCI T32CA009476), NPOD COBRE (NIH P20 GM104320), and the Fred & Pamela Buffett Cancer Center Support Grant (P30 CA036727).	[Anonymous], 2019, MULTIPLEX GENE EXPRE; Fisher KW, 2015, MOL CELL BIOL, V35, P3866, DOI 10.1128/MCB.00528-15; Kortum RL, 2004, MOL CELL BIOL, V24, P4407, DOI 10.1128/MCB.24.10.4407-4416.2004; McMillan EA, 2019, CELL CHEM BIOL, V26, P1380, DOI 10.1016/j.chembiol.2019.07.008; Potts MB, 2013, SCI SIGNAL, V6, DOI 10.1126/scisignal.2004657; Stegmaier K, 2004, NAT GENET, V36, P257, DOI 10.1038/ng1305	6	1	1	0	1	NATURE PUBLISHING GROUP	LONDON	MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND		2052-4463		SCI DATA	Sci. Data	JAN 21	2020	7	1								10.1038/s41597-020-0365-2			9	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	KI6DK	WOS:000511439400004	31964871	gold, Green Published			2022-04-25	
J	de Nigris, F; Balestrieri, ML; Napoli, C				de Nigris, Filomena; Balestrieri, Maria Luisa; Napoli, Claudio			Targeting c-Myc, Ras and IGF cascade to treat cancer and vascular disorders	CELL CYCLE			English	Review						c-Myc; Ras; IGF; cancer; atherosclerosis	GROWTH-FACTOR-I; SMOOTH-MUSCLE-CELLS; HUMAN ATHEROSCLEROTIC PLAQUES; ANTISENSE OLIGONUCLEOTIDES; COLON-CANCER; CARDIOVASCULAR-DISEASES; CAROTID ATHEROSCLEROSIS; HYPERLIPIDEMIC RABBITS; MORPHOLINO OLIGOMER; BINDING PROTEIN-3	Cancer and vascular diseases remain the predominant causes of morbidity and mortality in industrialized countries worldwide. The course of atherosclerosis with initiation, progression, and complication parallels the three stages of carcinogenesis with induction, growth, and invasion of tissue and neoangiogenesis. Within this framework, the oncogene c-Myc and growth factors pathways are acquiring increasing importance. Insulin-like growth factor-1 (IGF-1) pathway emerges among them for its versatile pleiotropic actions. A number of genes that permit extensive communication between IGF-1-AKT, p53, and mammalian target of rapamycin ( mTOR) pathways have been identified. In turn these pathways lead to p53 transcriptional program, the forkhead transcriptional programs, autophagy, and translational controls, which determine cell growth or arrest, cell survival or death. The increased understanding of the extensive communication and coordination between all these pathways may enable to targeting these events and to prevent neoplastic and vascular diseases. Great effort has been focused on the development of new agents designed to target various steps of c-Myc, Ras, and IGF cascade. However, what have we recently learned about their safety and effectiveness? Here, we review the very recent advances in the identification of novel inhibitors as well as antisense oligonuleotides (ASOs) and siRNA that are proving their usefulness in ongoing clinical trials both in therms of toxicity and specificity.	Univ Naples Federico II, Dept Gen Pathol, Sch Med 1, Div Clin Pathol, I-80134 Naples, Italy; Univ Naples Federico II, Excellence Res Ctr Cardiovasc Dis, Sch Med 1, I-80134 Naples, Italy; Univ Naples Federico II, Dept Chem Biol & Phys, Sch Med 1, I-80134 Naples, Italy		Napoli, C (corresponding author), Univ Naples Federico II, Dept Gen Pathol, Sch Med 1, Div Clin Pathol, Comlesso S Andrea Dame,Via L Crecchio 7, I-80134 Naples, Italy.	claunap@tin.it		Balestrieri, Maria Luisa/0000-0001-6001-1789; de nigris, filomena/0000-0002-2322-1557; Napoli, Claudio/0000-0002-5455-555X			Akagi Y, 1998, CANCER RES, V58, P4008; Andre F, 2004, ONCOGENE, V23, P1177, DOI 10.1038/sj.onc.1207238; Andreassi MG, 2000, ENVIRON MOL MUTAGEN, V35, P265, DOI 10.1002/1098-2280(2000)35:4<265::AID-EM1>3.0.CO;2-M; Appels NMGM, 2005, ONCOLOGIST, V10, P565, DOI 10.1634/theoncologist.10-8-565; Bayes-Genis A, 2000, CIRC RES, V86, P125, DOI 10.1161/01.RES.86.2.125; BENDITT EP, 1973, P NATL ACAD SCI USA, V70, P1753, DOI 10.1073/pnas.70.6.1753; 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J	Yeon, M; Lee, S; Lee, JE; Jung, HS; Kim, Y; Jeoung, D				Yeon, Minjeong; Lee, Seungheon; Lee, Joo-Eun; Jung, Hyun Suk; Kim, Youngmi; Jeoung, Dooil			CAGE-miR-140-5p-Wnt1 Axis Regulates Autophagic Flux, Tumorigenic Potential of Mouse Colon Cancer Cells and Cellular Interactions Mediated by Exosomes	FRONTIERS IN ONCOLOGY			English	Article						cancer associated gene CAGE; cellular interactions; exosomes; micro RNA-140-5p; tumor microenvironment; wnt1	CANCER/TESTIS ANTIGEN CAGE; FEEDBACK LOOP; MAST-CELLS; EXPRESSION; PROLIFERATION; ACTIVATION; RESISTANCE; INHIBITION; INCREASES; CISPLATIN	Although the cancer/testis antigen CAGE has been implicated in tumorigenesis, the molecular mechanisms of CAGE-promoted tumorigenesis remain largely unknown. CT26(Flag-CAGE) cells, CT26 (mouse colon cancer cells) cells stably expressing CAGE, were established to investigate CAGE-promoted tumorigenesis. Down-regulation of CAGE led to decreased autophagic flux in CT26(Flag-CAGE) cells. CAGE interacted with Beclin1, a mediator of autophagy. The CT26(Flag-CAGE) cells showed enhanced autophagosome formation and displayed greater tumor spheroid-forming potential than CT26 cells. MicroRNA array analysis revealed that CAGE decreased the expression of various microRNAs, including miR-140-5p, in CT26 cells. CAGE was shown to bind to the promoter sequences of miR-140-5p. MiR-140-5p inhibition increased the tumorigenic potential of and autophagic flux in CT26 cells. A miR-140-5p mimic exerted negative effects on the tumorigenic potential of CT26(Flag-CAGE) cells and autophagic flux in CT26(Flag-CAGE) cells. MiR-140-5p was predicted to bind to the 3 '-UTR of Wnt1. CT26(Flag-CAGE) cells showed higher expression of Wnt1 than CT26 cells. Down-regulation of Wnt1 decreased autophagic flux. Luciferase activity assays showed the direct regulation of wnt1 by miR-140-5p. Tumor tissue derived from the CT26(Flag-CAGE) cells revealed higher expressions of factors associated with activated mast cells and tumor-associated macrophages than tumor tissue derived from CT26 cells. Culture medium from the CT26(Flag-CAGE) cells increased autophagic flux in CT26 cells, mast cells and macrophages. Culture medium from the CT26(Flag-CAGE) cells increased CD163 and autophagic flux in CT26 cells, mast cells, and macrophages in a Wnt1-dependent manner. Exosomes from CT26(Flag-CAGE) cells increased autophagc flux in CT26 cells, mast cells, and macrophages. Exosomes from CT26(Flag-CAGE) cells increased the tumorigenic potential of CT26 cells. Wnt1 was shown to be present within the exosomes. Recombinant Wnt1 protein increased autophagic flux in CT26, mast cells, and macrophages. Recombinant wnt1 protein mediated interactions between the CT26 cells, mast cells, and macrophages. Our results showed novel roles for the CAGE-miR-140-5p-Wnt1 axis in autophagic flux and cellular interactions mediated by exosomes.	[Yeon, Minjeong; Lee, Seungheon; Lee, Joo-Eun; Jung, Hyun Suk; Jeoung, Dooil] Kangwon Natl Univ, Dept Biochem, Chuncheon Si, South Korea; [Kim, Youngmi] Hallym Univ, Coll Med, Inst New Frontier Res, Chuncheon Si, South Korea		Jeoung, D (corresponding author), Kangwon Natl Univ, Dept Biochem, Chuncheon Si, South Korea.	jeoungd@kangwon.ac.kr			National Research Foundation [2017R1A2A2A05001029, 2017M3A9G7072417, 2018R1D1A1B07043498]; BK21 plus Program; Korea Foundation for Cancer Research [KFCR-2018-002]	This work was supported by National Research Foundation Grants (2017R1A2A2A05001029, 2017M3A9G7072417, 2018R1D1A1B07043498), a grant from the BK21 plus Program. This work was also supported by Korea Foundation for Cancer Research (KFCR-2018-002).	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Oncol.	NOV 14	2019	9								1240	10.3389/fonc.2019.01240			20	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	JT8RC	WOS:000501249700001	31799196	Green Published, gold			2022-04-25	
J	Bhagwat, SV; Gokhale, PC; Crew, AP; Cooke, A; Yao, Y; Mantis, C; Kahler, J; Workman, J; Bittner, M; Dudkin, L; Epstein, DM; Gibson, NW; Wild, R; Arnold, LD; Houghton, PJ; Pachter, JA				Bhagwat, Shripad V.; Gokhale, Prafulla C.; Crew, Andrew P.; Cooke, Andy; Yao, Yan; Mantis, Christine; Kahler, Jennifer; Workman, Jennifer; Bittner, Mark; Dudkin, Lorina; Epstein, David M.; Gibson, Neil W.; Wild, Robert; Arnold, Lee D.; Houghton, Peter J.; Pachter, Jonathan A.			Preclinical Characterization of OSI-027, a Potent and Selective Inhibitor of mTORC1 and mTORC2: Distinct from Rapamycin	MOLECULAR CANCER THERAPEUTICS			English	Article							MAMMALIAN TARGET; KINASE INHIBITOR; IN-VITRO; GROWTH; AUTOPHAGY; THERAPY; RICTOR; ROLES	The phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway is frequently activated in human cancers, and mTOR is a clinically validated target. mTOR forms two distinct multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, metabolism, proliferation, and survival. Rapamycin and its analogues partially inhibit mTOR through allosteric binding to mTORC1, but not mTORC2, and have shown clinical utility in certain cancers. Here, we report the preclinical characterization of OSI-027, a selective and potent dual inhibitor of mTORC1 and mTORC2 with biochemical IC50 values of 22 nmol/L and 65 nmol/L, respectively. OSI-027 shows more than 100-fold selectivity for mTOR relative to PI3K alpha, PI3K beta, PI3K gamma, and DNA-PK. OSI-027 inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo. OSI-027 and OXA-01 (close analogue of OSI-027) potently inhibit proliferation of several rapamycin-sensitive and -insensitive nonengineered and engineered cancer cell lines and also, induce cell death in tumor cell lines with activated PI3K-AKT signaling. OSI-027 shows concentration-dependent pharmacodynamic effects on phosphorylation of 4E-BP1 and AKT in tumor tissue with resulting tumor growth inhibition. OSI-027 shows robust antitumor activity in several different human xenograft models representing various histologies. Furthermore, in COLO 205 and GEO colon cancer xenograft models, OSI-027 shows superior efficacy compared with rapamycin. Our results further support the important role of mTOR as a driver of tumor growth and establish OSI-027 as a potent anticancer agent. OSI-027 is currently in phase I clinical trials in cancer patients. Mol Cancer Ther; 10(8); 1394-406. (C) 2011 AACR.	[Bhagwat, Shripad V.] OSI Pharmaceut Inc, Biochem & Cellular Pharmacol, Canc Biol, Farmingdale, NY 11735 USA; [Crew, Andrew P.; Arnold, Lee D.] OSI Pharmaceut Inc, Canc Chem, Farmingdale, NY 11735 USA; [Gokhale, Prafulla C.; Cooke, Andy; Mantis, Christine; Workman, Jennifer; Bittner, Mark; Wild, Robert] OSI Pharmaceut Inc, Vivo Pharmacol, Boulder, CO USA; [Dudkin, Lorina; Houghton, Peter J.] Nationwide Childrens Hosp, Ctr Childhood Canc, Columbus, OH USA		Bhagwat, SV (corresponding author), OSI Pharmaceut Inc, Biochem & Cellular Pharmacol, Canc Biol, Farmingdale, NY 11735 USA.	shripad.bhagwat@us.astellas.com	Houghton, Peter/E-3265-2011	Kahler, Jennifer/0000-0002-4088-0888	NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA077776] Funding Source: NIH RePORTER; NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01 CA077776] Funding Source: Medline		Abraham RT, 2008, EXPERT OPIN THER TAR, V12, P209, DOI [10.1517/14728222.12.2.209, 10.1517/14728222.12.2.209 ]; Abraham RT, 1996, CURR OPIN IMMUNOL, V8, P412, DOI 10.1016/S0952-7915(96)80132-4; Bhagwat SV, 2010, CURR OPIN INVEST DR, V11, P638; Carayol N, 2010, P NATL ACAD SCI USA, V107, P12469, DOI 10.1073/pnas.1005114107; Chang YY, 2009, BIOCHEM SOC T, V37, P232, DOI 10.1042/BST0370232; CHEN X, 2007, Patent No. 20070112005; Chiang GG, 2007, TRENDS MOL MED, V13, P433, DOI 10.1016/j.molmed.2007.08.001; Choo AY, 2008, P NATL ACAD SCI USA, V105, P17414, DOI 10.1073/pnas.0809136105; Chresta CM, 2010, CANCER RES, V70, P288, DOI 10.1158/0008-5472.CAN-09-1751; Cloughesy TF, 2008, PLOS MED, V5, P139, DOI 10.1371/journal.pmed.0050008; Dancey J, 2010, NAT REV CLIN ONCOL, V7, P209, DOI 10.1038/nrclinonc.2010.21; Engelman JA, 2009, NAT REV CANCER, V9, P550, DOI 10.1038/nrc2664; Faivre S, 2006, NAT REV DRUG DISCOV, V5, P671, DOI 10.1038/nrd2062; Falcon BL, 2011, CANCER RES, V71, P1573, DOI 10.1158/0008-5472.CAN-10-3126; Feldman ME, 2009, PLOS BIOL, V7, P371, DOI 10.1371/journal.pbio.1000038; Garcia-Martinez JM, 2009, BIOCHEM J, V421, P29, DOI 10.1042/BJ20090489; Guertin DA, 2007, CANCER CELL, V12, P9, DOI 10.1016/j.ccr.2007.05.008; HOSAI H, 1999, CANCER RES, V59, P886; Jacinto E, 2004, NAT CELL BIOL, V6, P1122, DOI 10.1038/ncb1183; Jessen K, 2009, MOL CANCER THER, V8, pB148; JESSEN K, 2010, P AM ASS CANC RES 10; Ji QS, 2007, MOL CANCER THER, V6, P2158, DOI 10.1158/1535-7163.MCT-07-0070; Kim KW, 2006, J BIOL CHEM, V281, P36883, DOI 10.1074/jbc.M607094200; Lane HA, 2009, CURR OPIN CELL BIOL, V21, P219, DOI 10.1016/j.ceb.2009.01.016; LIU Y, 2009, AM ASS CANC RES SPL; Loewith R, 2002, MOL CELL, V10, P457, DOI 10.1016/S1097-2765(02)00636-6; Meric-Bernstam F, 2009, J CLIN ONCOL, V27, P2278, DOI 10.1200/JCO.2008.20.0766; O'Reilly KE, 2006, CANCER RES, V66, P1500, DOI 10.1158/0008-5472.CAN-05-2925; OCONNOR M, 2011, P AM ASS CANC RES 10; Proud CG, 2009, BIOCHEM SOC T, V37, P227, DOI 10.1042/BST0370227; Sarbassov DD, 2005, SCIENCE, V307, P1098, DOI 10.1126/science.1106148; Sarbassov DD, 2004, CURR BIOL, V14, P1296, DOI 10.1016/j.cub.2004.06.054; Thoreen CC, 2009, J BIOL CHEM, V284, P8023, DOI 10.1074/jbc.M900301200; Wullschleger S, 2006, CELL, V124, P471, DOI 10.1016/j.cell.2006.01.016; Yu K, 2010, CANCER RES, V70, P621, DOI 10.1158/0008-5472.CAN-09-2340	35	136	138	1	8	AMER ASSOC CANCER RESEARCH	PHILADELPHIA	615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA	1535-7163	1538-8514		MOL CANCER THER	Mol. Cancer Ther.	AUG	2011	10	8					1394	1406		10.1158/1535-7163.MCT-10-1099			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	804YR	WOS:000293692500010	21673091				2022-04-25	
J	Wang, WY; Wei, JL; Zhang, HR; Zheng, XR; Zhou, H; Luo, YJ; Yang, JG; Deng, QC; Huang, SQ; Fu, ZX				Wang, Wuyi; Wei, Jinlai; Zhang, Hairong; Zheng, Xiangru; Zhou, He; Luo, Yajun; Yang, Jianguo; Deng, Qican; Huang, Siqi; Fu, Zhongxue			PRDX2 promotes the proliferation of colorectal cancer cells by increasing the ubiquitinated degradation of p53	CELL DEATH & DISEASE			English	Article							TUMOR-SUPPRESSOR PROTEIN; TRANSCRIPTIONAL REPRESSION; MDM2; ACTIVATION; L11; INHIBITION; CHECKPOINT; MUTATIONS; AUTOPHAGY; ARREST	Colorectal cancer is the most common gastrointestinal cancer and causes severe damage to human health. PRDX2 is a member of the peroxiredoxin family reported to have a high level of expression in colorectal cancer. However, the mechanisms by which PRDX2 promotes the proliferation of colorectal cancer are still unclear. Here, the results indicated that PRDX2 expression was upregulated in colorectal cancer and closely correlated with poor prognosis. Functionally, PRDX2 promoted the proliferation of colorectal cancer cells. Mechanistically, PRDX2 could bind RPL4, reducing the interaction between RPL4 and MDM2. These findings demonstrate that the oncogenic property of PRDX2 may be attributed to its regulation of the RPL4-MDM2-p53 pathway, leading to p53 ubiquitinated degradation.	[Wang, Wuyi; Wei, Jinlai; Zhang, Hairong; Zheng, Xiangru; Zhou, He; Luo, Yajun; Yang, Jianguo; Deng, Qican; Huang, Siqi; Fu, Zhongxue] Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China		Fu, ZX (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China.	fzx19990521@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572319]; Chongqing Natural Science FoundationNatural Science Foundation of Chongqing [cstc2017jcyjAX0127]	The research project was supported by the National Natural Science Foundation of China (Grant No. 81572319; Project recipient: F.Z.) and Chongqing Natural Science Foundation (Grant No. cstc2017jcyjAX0127; Project recipient: W.J.).	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JUN 11	2021	12	6							605	10.1038/s41419-021-03888-1			10	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	SV0YJ	WOS:000663552600003	34117220	Green Published, gold			2022-04-25	
J	Kang, S; Kim, JE; Song, NR; Jung, SK; Lee, MH; Park, JS; Yeom, MH; Bode, AM; Dong, ZG; Lee, KW				Kang, Soouk; Kim, Jong-Eun; Song, Nu Ry; Jung, Sung Keun; Lee, Mee Hyun; Park, Jun Seong; Yeom, Myeong-Hun; Bode, Ann M.; Dong, Zigang; Lee, Ki Won			The Ginsenoside 20-O-beta-D-Glucopyranosyl-20(S)-Protopanaxadiol Induces Autophagy and Apoptosis in Human Melanoma via AMPK/JNK Phosphorylation	PLOS ONE			English	Article							HUMAN COLORECTAL-CANCER; COMPOUND-K; CELL-DEATH; B-RAF; ACTIVATION; MUTATIONS; NECROSIS; SURVIVAL; BRAF; RB1	Studies have shown that a major metabolite of the red ginseng ginsenoside Rb1, called 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (GPD), exhibits anticancer properties. However, the chemotherapeutic effects and molecular mechanisms behind GPD action in human melanoma have not been previously investigated. Here we report the anticancer activity of GPD and its mechanism of action in melanoma cells. GPD, but not its parent compound Rb1, inhibited melanoma cell proliferation in a dose-dependent manner. Further investigation revealed that GPD treatment achieved this inhibition through the induction of autophagy and apoptosis, while Rb1 failed to show significant effect at the same concentrations. The inhibitory effect of GPD appears to be mediated through the induction of AMPK and the subsequent attenuation of mTOR phosphorylation. In addition, GPD activated c-Jun by inducing JNK phosphorylation. Our findings suggest that GPD suppresses melanoma growth by inducing autophagic cell death and apoptosis via AMPK/JNK pathway activation. GPD therefore has the potential to be developed as a chemotherapeutic agent for the treatment of human melanoma.	[Kang, Soouk; Kim, Jong-Eun; Song, Nu Ry; Jung, Sung Keun; Lee, Ki Won] Seoul Natl Univ, Dept Agr Biotechnol, WCU Biomodulat Major, Seoul, South Korea; [Kang, Soouk; Kim, Jong-Eun; Song, Nu Ry; Jung, Sung Keun; Lee, Ki Won] Seoul Natl Univ, Ctr Food & Bioconvergence, Seoul, South Korea; [Kang, Soouk; Kim, Jong-Eun; Jung, Sung Keun; Lee, Mee Hyun; Bode, Ann M.; Dong, Zigang] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA; [Song, Nu Ry; Lee, Ki Won] Seoul Natl Univ, Adv Inst Convergence Technol, Suwon, South Korea; [Jung, Sung Keun] Korea Food Res Inst, Funct Food Resources Res Grp, Songnam, South Korea; [Park, Jun Seong; Yeom, Myeong-Hun] Amorepacif Corp R&D Ctr, Skin Res Inst, Yongin, South Korea; [Lee, Ki Won] Seoul Natl Univ, Inst Green Bio Sci & Technol, Res Inst Bio Food Ind, Pyeongchang, South Korea		Dong, ZG (corresponding author), Univ Minnesota, Hormel Inst, 801 16th Ave NE, Austin, MN 55912 USA.	zgdong@hi.umn.edu; kiwon@snu.ac.kr	kim, jong-eun/B-3550-2017; Lee, Ki Won/M-4114-2018	kim, jong-eun/0000-0002-5030-6126; 	World Class Institute Program [WCI2009-002]; Leap Research Program Grant through the National Research Foundation, Ministry of Science, ICT and Future Planning, Republic of Korea [2010-0029233]	This work was supported by the World Class Institute Program (WCI2009-002) and the Leap Research Program Grant (2010-0029233) through the National Research Foundation, Ministry of Science, ICT and Future Planning, Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Tian, W; Chen, SY				Tian Wei; Chen Si-yu			Recent advances in the molecular basis of anti-neoplastic mechanisms of oridonin	CHINESE JOURNAL OF INTEGRATIVE MEDICINE			English	Review						oridonin; anti-neoplasm; cell cycle arrest; apoptosis; autophagy	CARCINOMA HELA-CELLS; BREAST-CANCER CELLS; NF-KAPPA-B; INDUCED APOPTOSIS; RABDOSIA-RUBESCENS; SIGNALING PATHWAYS; COLORECTAL-CANCER; INDUCED AUTOPHAGY; LEUKEMIA-CELLS; CYCLE ARREST	Oridonin, a diterpenoid isolated from Rabdosia rubescens, has been proven to possess various pharmacological and physiological effects such as anti-inflammation, anti-bacterial, and anti-neoplastic, although in recent years, more attention has been paid to its anti-neoplastic effects. For example, oridonin can trigger cell cycle arrest, apoptosis, and autophagy in different neoplastic cell lines. This review summarizes the considerable knowledge about the action mechanisms of oridonin that has been studied in recent years. The present observations reveal the novel anti-neoplastic effects of oridonin, suggesting that it may be effective as a potent alternative or adjunct drug to conventional chemotherapy.	[Tian Wei; Chen Si-yu] Shanghai Jiao Tong Univ, Dept Oncol, Xinhua Hosp, Sch Medcine, Shanghai 200092, Peoples R China		Chen, SY (corresponding author), Shanghai Jiao Tong Univ, Dept Oncol, Xinhua Hosp, Sch Medcine, Shanghai 200092, Peoples R China.	siyu.chen@shsmu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81274142, 30300139]; Natural Science Foundation of Science and Technology Commission of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [11ZR1423400]; Key Project of Shanghai Municipal Education CommissionScience & Technology Commission of Shanghai Municipality (STCSM) [07zz43]	Supported by National Natural Science Foundation of China (No. 81274142, No. 30300139), Natural Science Foundation of Science and Technology Commission of Shanghai Municipality (No. 11ZR1423400), Key Project of Shanghai Municipal Education Commission (No. 07zz43)	Cai JY, 1998, BBA-BIOENERGETICS, V1366, P139, DOI 10.1016/S0005-2728(98)00109-1; Chen Jun-hui, 2008, Zhonghua Zhongliu Zazhi, V30, P89; Chen S, 2005, INT J ONCOL, V26, P579; Cheng Y, 2009, ARCH BIOCHEM BIOPHYS, V490, P70, DOI 10.1016/j.abb.2009.08.011; Cheng Y, 2009, FEBS J, V276, P1291, DOI 10.1111/j.1742-4658.2008.06864.x; Cui Q, 2007, ACTA PHARMACOL SIN, V28, P1057, DOI 10.1111/j.1745-7254.2007.00588.x; Cui Q, 2006, J PHARMACOL SCI, V101, P230, DOI 10.1254/jphs.FPJ06003X; Cui Q, 2007, J PHARMACOL SCI, V105, P317, DOI 10.1254/jphs.FP0070336; Ding L, 2009, NAT PROD RES, V15, P1; DiPietrantonio AM, 1998, INT J CANCER, V78, P53, DOI 10.1002/(SICI)1097-0215(19980925)78:1<53::AID-IJC10>3.3.CO;2-C; Fan QX, 1997, CHIN J SURGERY INTEG, V3, P380; FUJITA E, 1976, EXPERIENTIA, V32, P203, DOI 10.1007/BF01937766; Gao F, 2010, INT J LAB HEMATOL, V32, pE114, DOI 10.1111/j.1751-553X.2009.01147.x; Gao FH, 2010, BMC CANCER, V10, DOI 10.1186/1471-2407-10-610; Han QB, 2003, CHEM PHARM BULL, V51, P790, DOI 10.1248/cpb.51.790; HARTWELL LH, 1994, SCIENCE, V266, P1821, DOI 10.1126/science.7997877; He Xu-jun, 2009, Zhonghua Wei Chang Wai Ke Za Zhi, V12, P607; Hsieh TC, 2005, BIOCHEM BIOPH RES CO, V337, P224, DOI 10.1016/j.bbrc.2005.09.040; Hu HZ, 2007, ACTA PHARMACOL SIN, V28, P1819, DOI 10.1111/j.1745-7254.2007.00667.x; Huang J, 2008, J PHARMACOL SCI, V107, P370, DOI 10.1254/jphs.08044FP; Ikezoe T, 2005, MOL CANCER THER, V4, P578, DOI 10.1158/1535-7163.MCT-04-0277; Ikezoe T, 2003, INT J ONCOL, V23, P1187; Jiang JF, 2011, BIOCHEM BIOPH RES CO, V412, P55, DOI 10.1016/j.bbrc.2011.07.036; Jilani K, 2011, ARCH BIOCHEM BIOPHYS, V511, P14, DOI 10.1016/j.abb.2011.05.001; Jin HY, 2011, J GASTROEN HEPATOL, V26, P706, DOI 10.1111/j.1440-1746.2010.06500.x; Jin S, 2007, CANCER BIOL THER, V6, P261, DOI 10.4161/cbt.6.2.3621; Kang N, 2010, J NAT PROD, V73, P1058, DOI 10.1021/np9008199; Kang N, 2010, CANCER LETT, V294, P147, DOI 10.1016/j.canlet.2010.01.032; Li D, 2008, J ASIAN NAT PROD RES, V10, P77, DOI 10.1080/10286020701273866; Liu C.J., 1998, CHIN PHARM J, V33, P577; Liu JW, 2007, INT IMMUNOPHARMACOL, V7, P945, DOI 10.1016/j.intimp.2007.03.001; Liu JJ, 2006, AM J HEMATOL, V81, P86, DOI 10.1002/ajh.20524; Liu JJ, 2005, NEOPLASMA, V52, P225; Liu JJ, 2005, LEUKEMIA LYMPHOMA, V46, P593, DOI 10.1080/10428190400019800; Liu JJ, 2004, ANN HEMATOL, V83, P691, DOI 10.1007/s00277-004-0919-y; Liu Yan-qiu, 2005, Zhongguo Zhong Yao Za Zhi, V30, P1856; Meier P, 2000, NATURE, V407, P796, DOI 10.1038/35037734; Ren KK, 2006, J ETHNOPHARMACOL, V103, P176, DOI 10.1016/j.jep.2005.07.020; Vousden KH, 2007, NAT REV MOL CELL BIO, V8, P275, DOI 10.1038/nrm2147; Wang H, 2007, MED J QILU CHIN, V22, P339; Wang H, 2011, PHYTOMEDICINE, V18, P163, DOI 10.1016/j.phymed.2010.06.011; Wang H, 2010, ONCOL REP, V24, P647, DOI 10.3892/or_00000903; Wilson MR, 1998, BIOCHEM CELL BIOL, V76, P573, DOI 10.1139/bcb-76-4-573; Ye Li-hong, 2010, Zhonghua Yi Xue Za Zhi, V90, P2984; YIN XM, 1994, NATURE, V369, P321, DOI 10.1038/369321a0; Zhan YH, 2009, BIOCHEM BIOPH RES CO, V378, P273, DOI 10.1016/j.bbrc.2008.11.038; Zhang JF, 2006, HEPATOL RES, V35, P104, DOI 10.1016/j.hepres.2006.03.007; Zhang Jun-Feng, 2006, Zhongguo Zhong Yao Za Zhi, V31, P1811; Zhang YH, 2011, ACTA PHARMACOL SIN, V32, P1266, DOI 10.1038/aps.2011.92; Zhang YH, 2009, ARCH BIOCHEM BIOPHYS, V489, P25, DOI 10.1016/j.abb.2009.07.017; Zhu Y, 2007, PHARMAZIE, V62, P439, DOI 10.1691/ph.2007.6.6691	51	29	35	5	56	SPRINGER	NEW YORK	233 SPRING ST, NEW YORK, NY 10013 USA	1672-0415	1993-0402		CHIN J INTEGR MED	Chin. J. Integr. Med.	APR	2013	19	4					315	320		10.1007/s11655-013-1437-3			6	Integrative & Complementary Medicine	Science Citation Index Expanded (SCI-EXPANDED)	Integrative & Complementary Medicine	117QA	WOS:000316967000010	23546635				2022-04-25	
J	Kouhbanani, MAJ; Sadeghipour, Y; Sarani, M; Sefidgar, E; Ilkhani, S; Amani, AM; Beheshtkhoo, N				Kouhbanani, Mohammad Amin Jadidi; Sadeghipour, Yasin; Sarani, Mina; Sefidgar, Erfan; Ilkhani, Saba; Amani, Ali Mohammad; Beheshtkhoo, Nasrin			The inhibitory role of synthesized Nickel oxide nanoparticles against Hep-G2, MCF-7, and HT-29 cell lines: the inhibitory role of NiO NPs against Hep-G2, MCF-7, and HT-29 cell lines	GREEN CHEMISTRY LETTERS AND REVIEWS			English	Article						Nickel oxide nanoparticles; cyclic voltammetry; Hep-G2; MTT assay	CATALYTIC-ACTIVITY; OXIDATIVE STRESS; GREEN SYNTHESIS; ZINC-OXIDE; SOL-GEL; EXTRACT; AUTOPHAGY; DECOMPOSITION	Nickel oxide nanoparticles (NiO NPs) were synthesized via the facile sol-gel method. The synthesized NiO NPs were characterized using X-ray diffraction (XRD), Field-Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy (TEM), Raman and Fourier Transform Infrared (FT-IR) techniques. The effect of particle size was analyzed on structural alterations, electrochemical behaviors, and cytotoxic effect of synthesized NiO NPs. According to TEM results, the particle sizes of synthesized NiO NPs were 8.2, 15.4, and 21.7 nm at 300, 400, and 500 degrees C, respectively. Electrochemical behaviors of synthesized NiO NPs were assessed through the cyclic voltammetry (CV) technique. The results showed that the magnitude of the current density was decreased in treated samples exposed to higher temperature values. The cytotoxic activity of synthesized nanoparticles was investigated against human liver cancer cell (Hep-G2), breast cancer cell (MCF-7), and colon cancer cell (HT-29) lines using the MTT assay. The results demonstrated that synthesized NiO NPs had higher cytotoxicity at 300 C than at 400 and 500 C, because of their small particle size. Thus, synthesized NiO NPs exhibit acceptable cytotoxic effects against Hep-G2, MCF-7, and HT-29 cancer cell lines so that they could be a good choice for cancer treatment.	[Kouhbanani, Mohammad Amin Jadidi; Sadeghipour, Yasin; Amani, Ali Mohammad; Beheshtkhoo, Nasrin] Shiraz Univ Med Sci, Sch Adv Med Sci & Technol, Dept Med Nanotechnol, Shiraz, Iran; [Sarani, Mina] Zabol Univ Med Sci, Zabol Med Plants Res Ctr, Zabol, Iran; [Sefidgar, Erfan] Inst Adv Studies Basic Sci, Dept Biol Sci, Zanjan, Iran; [Ilkhani, Saba] Shahid Beheshti Univ, Sch Med, Dept Biol & Anat Sci, Tehran, Iran; [Amani, Ali Mohammad] Shiraz Univ Med Sci, Pharmaceut Sci Res Ctr, Shiraz, Iran		Amani, AM; Beheshtkhoo, N (corresponding author), Shiraz Univ Med Sci, Sch Adv Med Sci & Technol, Dept Med Nanotechnol, Shiraz, Iran.	Aliamani1400@gmail.com; beheshtkhoo.nano@gmail.com			Shiraz University of Medical Science [1396-0174-1526B]	This work was financially supported by research Grant of Shiraz University of Medical Science (No.1396-0174-1526B)	Azad MB, 2009, ANTIOXID REDOX SIGN, V11, P777, DOI 10.1089/ARS.2008.2270; Azar BE, 2020, OPTIK, V208, DOI 10.1016/j.ijleo.2019.164129; Babu A, 2014, AAPS PHARMSCITECH, V15, P709, DOI 10.1208/s12249-014-0089-8; Behzad F, 2021, J IND ENG CHEM, V94, P92, DOI 10.1016/j.jiec.2020.12.005; Behzad F, 2020, SOFT MATER, V18, P471, DOI 10.1080/1539445X.2020.1716800; Boukhachem A, 2014, MATER SCI ENG B-ADV, V188, P72, DOI 10.1016/j.mseb.2014.06.001; Buazar F, 2016, J EXP NANOSCI, V11, P175, DOI 10.1080/17458080.2015.1039610; Buazar F, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-51663-2; Buazar F, 2019, GREEN PROCESS SYNTH, V8, P691, DOI 10.1515/gps-2019-0040; Buazar F, 2016, STARCH-STARKE, V68, P796, DOI 10.1002/star.201500347; Cho YL, 2020, FREE RADICAL BIO MED, V153, P173, DOI 10.1016/j.freeradbiomed.2020.03.027; Dalvand H, 2014, MATER LETT, V130, P54, DOI 10.1016/j.matlet.2014.05.057; DISLICH H, 1986, J NON-CRYST SOLIDS, V80, P115, DOI 10.1016/0022-3093(86)90384-4; Fardood ST, 2020, MATER RES EXPRESS, V7, DOI 10.1088/2053-1591/ab6c8d; Filomeni G, 2015, CELL DEATH DIFFER, V22, P377, DOI 10.1038/cdd.2014.150; Ghaz-Jahanian MA, 2015, MOL BIOTECHNOL, V57, P201, DOI 10.1007/s12033-014-9816-3; Gholizadeh BS, 2018, INT J BIOL MACROMOL, V116, P786, DOI 10.1016/j.ijbiomac.2018.05.104; Ghoran Salar Hafez, 2020, Nanomedicine Research Journal, V5, P20, DOI 10.22034/nmrj.2020.01.003; Gleiter H, 2000, ACTA MATER, V48, P1, DOI 10.1016/S1359-6454(99)00285-2; Hu Z, 2012, CARBON, V50, P994, DOI 10.1016/j.carbon.2011.10.002; Ibraheem F, 2019, MATER LETT, V234, P129, DOI 10.1016/j.matlet.2018.09.075; Khalafi T, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-43368-3; Kharissova OV, 2013, TRENDS BIOTECHNOL, V31, P240, DOI 10.1016/j.tibtech.2013.01.003; Kodama RH, 1997, PHYS REV LETT, V79, P1393, DOI 10.1103/PhysRevLett.79.1393; Koopi H, 2018, CERAM INT, V44, P8940, DOI 10.1016/j.ceramint.2018.02.091; Krishnamoorthy K, 2012, J MATER CHEM, V22, P24610, DOI 10.1039/c2jm35087d; Kumar PV, 2019, SN APPL SCI, V1, DOI 10.1007/s42452-019-1113-0; McHenry ME, 2000, ACTA MATER, V48, P223, DOI 10.1016/S1359-6454(99)00296-7; Mehr ES, 2018, J MATER SCI-MATER EL, V29, P1333, DOI 10.1007/s10854-017-8039-3; Moavi J, 2021, SCI REP-UK, V11, DOI 10.1038/s41598-021-85832-z; Moradnia F, 2021, J CLEAN PROD, V288, DOI 10.1016/j.jclepro.2020.125632; Moradnia F, 2020, J PHOTOCH PHOTOBIO A, V392, DOI 10.1016/j.jphotochem.2020.112433; Nasirmoghadas P, 2021, BIOTECHNOL PROGR, V37, DOI 10.1002/btpr.3070; Nath D, 2013, ENVIRON TOXICOL PHAR, V36, P997, DOI 10.1016/j.etap.2013.09.002; OHNO H, 1992, PHYS REV LETT, V68, P2664, DOI 10.1103/PhysRevLett.68.2664; Rasmussen JW, 2010, EXPERT OPIN DRUG DEL, V7, P1063, DOI 10.1517/17425247.2010.502560; Rezazadeh NH, 2020, SCI REP-UK, V10, DOI 10.1038/s41598-020-76726-7; Sasidharan A, 2011, NANOSCALE, V3, P3657, DOI 10.1039/c1nr10272a; Sorbiun M., 2018, NANOCHEMISTRY RES, V3, P1, DOI 10.22036/ncr.2018.01.001; Sriram MI, 2010, INT J NANOMED, V5, P753, DOI 10.2147/IJN.S11727; Wang YP, 2005, THERMOCHIM ACTA, V437, P106, DOI 10.1016/j.tca.2005.06.027; Winkler E, 2005, PHYS REV B, V72, DOI 10.1103/PhysRevB.72.132409; Yeganeh MS, 2019, MATER RES EXPRESS, V6, DOI 10.1088/2053-1591/ab6637; Zhang FF, 2014, CHEM ENG J, V256, P365, DOI 10.1016/j.cej.2014.07.007	44	3	3	0	2	TAYLOR & FRANCIS LTD	ABINGDON	2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND	1751-8253	1751-7192		GREEN CHEM LETT REV	Green Chem. Lett. Rev.	JUL 3	2021	14	3					443	453		10.1080/17518253.2021.1939435			11	Chemistry, Multidisciplinary; Green & Sustainable Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Science & Technology - Other Topics	SV2BV	WOS:000663630800001		gold			2022-04-25	
J	Zou, L; Sun, P; Zhang, L				Zou, Lei; Sun, Peng; Zhang, Lei			miR-651-3p Enhances the Sensitivity of Hepatocellular Carcinoma to Cisplatin via Targeting ATG3-Mediated Cell Autophagy	JOURNAL OF ONCOLOGY			English	Article							GASTRIC-CANCER; COLON-CANCER; PROLIFERATION; METASTASIS; RESISTANCE; INVASION; PROMOTES; AXIS; ATG3; HCC	Drug resistance is a major challenge for hepatocellular carcinoma (HCC) treatment in a clinic, which limits the therapeutic effect of the chemotherapeutic drugs, including cisplatin (CDDP), in this disease. Mounting evidence has identified that miRNAs dysfunction is related to the resistance of tumor cells to CDDP, and miR-651-3p has been identified as a tumor inhibitor to suppress the progression of multiple tumors. However, the role of miR-651-3p in HCC remains unclear. In this study, the relative expression of miR-651-3p in HCC tissues and cell lines were measured, and the functions of miR-651-3p were also observed by CCK-8 assay, flow cytometry assay, and Western blot. Moreover, the downstream target of miR-651-3p was predicted and verified via TargetScan and dual-luciferase reporter assay, and its functions were also investigated. The results showed that miR-651-3p was significantly downregulated in HCC tissues and cell lines, and the decreased miR-651-3p was also observed in CDDP-induced cells. miR-651-3p upregulation could effectively inhibit the proliferation and induce the apoptosis of R-HepG2. It was also found that ATG3 was a downstream target of miR-651-3p, and ATG3 was highly upregulated in HCC tissues. Moreover, the upregulated ATG3 could partly reverse the effects of miR-651-3p on R-HepG2. Besides, miR-651-3p involved the autophagy pathway of the HCC cells via targeting ATG3. In conclusion, miR-651-3p could regulate the autophagy to enhance the sensitivity of HepG2 cells to CDDP via targeting ATG3.	[Zou, Lei; Sun, Peng; Zhang, Lei] Zibo Cent Hosp, Dept Gastroenterol, Zibo 255036, Shandong, Peoples R China		Zhang, L (corresponding author), Zibo Cent Hosp, Dept Gastroenterol, Zibo 255036, Shandong, Peoples R China.	shibayej@163.com					Caines A, 2020, CLIN LIVER DIS, V24, P535, DOI 10.1016/j.cld.2020.06.001; Feng Y, 2020, EXP CELL RES, V394, DOI 10.1016/j.yexcr.2020.112162; Hu GF, 2019, INT J CLIN EXP PATHO, V12, P3185; Huang W, 2019, CANCER MANAG RES, V11, P10275, DOI 10.2147/CMAR.S226828; Kang Y, 2019, ONCOTARGETS THER, V12, P10787, DOI 10.2147/OTT.S226044; Lee E, 2014, AUTOPHAGY, V10, P572, DOI 10.4161/auto.27649; Li XY, 2020, J CELL PHYSIOL, V235, P3402, DOI 10.1002/jcp.29230; Liao YJ, 2020, MOLECULES, V25, DOI 10.3390/molecules25122856; Lin S, 2020, ONCOTARGETS THER, V13, P337, DOI 10.2147/OTT.S220302; Liu Z, 2018, CANCER BIOMARK, V22, P453, DOI 10.3233/CBM-171075; Ma K, 2017, AUTOPHAGY, V13, P579, DOI 10.1080/15548627.2016.1272742; Nazio F, 2019, CELL DEATH DIFFER, V26, P690, DOI 10.1038/s41418-019-0292-y; Peng YF, 2013, AUTOPHAGY, V9, P2056, DOI 10.4161/auto.26398; Regan-Fendt K, 2020, CANCERS, V12, DOI 10.3390/cancers12102730; Ren Y, 2020, AM J TRANSL RES, V12, P825; Ruan Q, 2020, INT J CANCER, V147, P1519, DOI 10.1002/ijc.32899; Tharmalingam MD, 2020, BMC MED, V18, DOI 10.1186/s12916-020-01844-y; Wang H, 2018, ONCOL REP, V39, P247, DOI 10.3892/or.2017.6088; Wang JC, 2019, J CELL BIOCHEM, V120, P18816, DOI 10.1002/jcb.29197; Wei L, 2019, NAT COMMUN, V10, DOI 10.1038/s41467-019-12606-7; Wojciechowska N, 2019, PLANTA, V250, P1789, DOI 10.1007/s00425-019-03265-5; Xiao Y, 2021, P NATL ACAD SCI USA, V118, DOI 10.1073/pnas.2015808118; Yu SF, 2021, CELL DEATH DIS, V12, DOI 10.1038/s41419-021-03432-1; Zhang S, 2020, DNA CELL BIOL, V39, P379, DOI 10.1089/dna.2019.5145; Zhang YS, 2018, LIFE SCI, V207, P451, DOI 10.1016/j.lfs.2018.06.034; Zhao HF, 2020, J CELL BIOCHEM, V121, P1690, DOI 10.1002/jcb.29404; Zhou Y, 2019, GENOMICS, V111, P1862, DOI 10.1016/j.ygeno.2018.12.009; Zhou Y, 2018, J EXP CLIN CANC RES, V37, DOI 10.1186/s13046-018-0965-2	28	0	0	0	1	HINDAWI LTD	LONDON	ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND	1687-8450	1687-8469		J ONCOL	J. Oncol.	AUG 19	2021	2021								5391977	10.1155/2021/5391977			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	UJ2AF	WOS:000691094200002	34457004	gold, Green Published			2022-04-25	
J	Yang, Z; Chen, YS; Wei, XY; Wu, DJ; Min, ZJ; Quan, YJ				Yang, Zhou; Chen, Yusheng; Wei, Xiyi; Wu, Dejun; Min, Zhijun; Quan, Yingjun			Upregulated NTF4 in colorectal cancer promotes tumor development via regulating autophagy	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						neurotrophin-4; colorectal cancer; epithelial-to-mesenchymal transition; autophagy; mitogen-activated protein kinase pathway	GENE-EXPRESSION; APOPTOSIS; PATHWAYS; CELLS; EMT	Autophagy plays a key role in colorectal cancer (CRC) development and reduces the sensitivity of CRC cells to treatment. The present study reported a novel tumor-suppressive role for autophagy, which was demonstrated to be regulated through the novel oncogene neurotrophin-4 (NTF4). NTF4 was significantly overexpressed in tumor tissue compared with non-tumor mucosa, and the upregulation of NTF4 in CRC was associated with poor overall survival and advanced TNM stage. The genetic knockdown of NTF4 using short hairpin RNA in CRC cells prevented epithelial-to-mesenchymal transition and activated autophagy; this was regulated through the interaction between autophagy-associated gene 5 (Atg5) and the mitogen-activated protein kinase pathway. In addition, the knockdown of NTF4 inhibited cell invasion, migration, proliferation and colony formation, and promoted cell cycle arrest. Treatment of the cells with the autophagy inhibitor chloroquine (CQ) rescued these functions and promoted cell invasion, migration, proliferation and colony formation. Finally, the knockdown of NTF4 inhibited the growth of subcutaneous xenografts in Balb/c-nu mice. In conclusion, these findings suggested that NTF4 may be a diagnostic marker associated with the overall survival and progression of patients with CRC. NTF4 was found to promote tumorigenesis and CRC development through autophagy regulation.	[Yang, Zhou; Chen, Yusheng; Wu, Dejun; Min, Zhijun; Quan, Yingjun] Fudan Univ, Pudong Med Ctr, Shanghai Pudong Hosp, Dept Gen Surg, 2800 Gongwei Rd, Shanghai 201399, Peoples R China; [Wei, Xiyi] Nanjing Med Univ, Clin Med Coll 1, Nanjing 210029, Jiangsu, Peoples R China; [Quan, Yingjun] Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Shanghai 201399, Peoples R China		Min, ZJ; Quan, YJ (corresponding author), Fudan Univ, Pudong Med Ctr, Shanghai Pudong Hosp, Dept Gen Surg, 2800 Gongwei Rd, Shanghai 201399, Peoples R China.	minzhijun@126.com; qyjasmine@126.com			Academic Leaders Training Program - Pudong Health Bureau of Shanghai [PWRd2016-05]; Scientific Research Foundation by Pudong Hospital [YJ2020-01]	The present study was funded by The Academic Leaders Training Program Supported by Pudong Health Bureau of Shanghai (grant no. PWRd2016-05) and the Scientific Research Foundation provided by Pudong Hospital affiliated to Fudan University (grant no. YJ2020-01).	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J. Oncol.	JUN	2020	56	6					1442	1454		10.3892/ijo.2020.5027			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	LJ8IE	WOS:000530403800008	32236587	Green Published, hybrid			2022-04-25	
J	BonakdarYazdi, B; Khodagholi, F; Shaerzadeh, F; Sharifzadeh, A; Ahmadi, R; Sanati, M; Mehdizadeh, H; Payandehmehr, B; Vali, L; Jahromi, MM; Taghizadeh, G; Sharifzadeh, M				BonakdarYazdi, Behnoosh; Khodagholi, Fariba; Shaerzadeh, Fatemeh; Sharifzadeh, Azadeh; Ahmadi, Ramesh; Sanati, Mehdi; Mehdizadeh, Hajar; Payandehmehr, Borna; Vali, Leila; Jahromi, Mehrnoush Moghaddasi; Taghizadeh, Ghorban; Sharifzadeh, Mohammad			The effect of arsenite on spatial learning: Involvement of autophagy and apoptosis	EUROPEAN JOURNAL OF PHARMACOLOGY			English	Article						Sodium arsenite; Autophagy; Apoptosis; Alzheimer disease; Spatial learning; Caspase-3; LC3	CASPASE-MEDIATED CLEAVAGE; COLON-CANCER CELLS; MORRIS WATER MAZE; SODIUM ARSENITE; CREB PHOSPHORYLATION; BECLIN 1; REGULATES AUTOPHAGY; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS; NERVOUS-SYSTEM	Spatial learning plays a major role in one's information recording. Arsenic is one of ubiquitous environmental toxins with known neurological effects. However, studies investigating the effects of arsenic on spatial learning and related mechanisms are limited. This study was planned toexaminethe effects of bilateral intra-hippocampal infusion of different concentrations of sodium arsenite (5, 10 and 100 nM, 5 mu l/side) on spatial learning in Wistar rats. Moreover, we evaluated levels of LC3-II, Atg7 and Atg12 as reliable biomarkers of autophagy and caspase-3 and Bax/Bcl-2 ratio as indicators of apoptosis in the hippocampus. Interestingly, low concentrations of sodium arsenite (5 and 10 nM) significantly increased spatial acquisition but pre-training administration of sodium arsenite100 nM did not significantly alter spatial learning. LC3-II levels were significantly increased in groups treated with sodium arsenite 5 and 10 nM and decreased in the group receiving arsenite 100 nM compared to the control group. Atg7 and Atg12 levels were obviously higher in all groups treated with sodium arsenite compared to control. However, caspase-3 cleavage and Bax/Bcl-2 ratio were notably greater in 100 nM, and lesser in 5 nM arsenite group in comparison with control animals. The results of this study showed that the low concentrations of sodium arsenite could facilitate spatial learning. This facilitation could be attributed to neuronal autophagy induced by low concentrations of sodium arsenite. These findings may help to clarify the regulatory pathways for apoptosis and autophagy balance due to sodium arsenite.	[BonakdarYazdi, Behnoosh; Sanati, Mehdi; Mehdizadeh, Hajar; Payandehmehr, Borna; Taghizadeh, Ghorban; Sharifzadeh, Mohammad] Univ Tehran Med Sci, Toxicol & Poisoning Res Ctr, Fac Pharm, Dept Pharmacol & Toxicol, Tehran, Iran; [Khodagholi, Fariba] Shahid Beheshti Univ Med Sci, Neurosci Res Ctr, Tehran, Iran; [Shaerzadeh, Fatemeh] Hormozgan Univ Med Sci, Dept Physiol, Fac Med, Bandar Abbas, Iran; [Sharifzadeh, Azadeh; Ahmadi, Ramesh] Azad Univ, Dept Physiol, Qom, Iran; [Mehdizadeh, Hajar; Taghizadeh, Ghorban; Sharifzadeh, Mohammad] Univ Tehran Med Sci, Sch Adv Technol Med, Dept Neurosci, Tehran, Iran; [Vali, Leila] Kuwait Univ, Fac Allied Hlth Sci, Dept Med Lab Sci, Sulibikhat, Kuwait; [Jahromi, Mehrnoush Moghaddasi] Lorestan Univ Med Sci, Sch Med, Dept Physiol, Khorramabad, Iran; [Taghizadeh, Ghorban] Iran Univ Med Sci, Fac Rehabil Sci, Dept Occupat Therapy, Tehran, Iran		Sharifzadeh, M (corresponding author), Univ Tehran Med Sci, Fac Pharm, Dept Pharmacol & Toxicol, Tehran, Iran.	msharifzadeh@sina.tums.ac.ir	Taghizadeh, Ghorban/L-8609-2018; Taghizadeh, Ghorban/AAD-7167-2022; Khodagholi, Fariba/AAZ-4436-2020; Sanati, Mehdi/AAH-6634-2021	Taghizadeh, Ghorban/0000-0002-0145-9599; Taghizadeh, Ghorban/0000-0002-0145-9599; 	Tehran University of Medical Sciences (TUMS)Tehran University of Medical Sciences [92-02-33-23268]; Lorestan University of Medical Sciences [1283]	This work was supported by funds (No. 92-02-33-23268) from the Tehran University of Medical Sciences (TUMS) and Lorestan University of Medical Sciences (No. 1283). We thank Dr. Kian Azami and Dr. Ali Hosseini for their generous scientific advices and Mr. Ali Kazemi and Mr. Mehdi Gholami for their technical assistance.	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J. Pharmacol.	FEB 5	2017	796						54	61		10.1016/j.ejphar.2016.12.023			8	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	EJ9EL	WOS:000393529300007	27993642				2022-04-25	
J	Park, SH; Park, SJ; Kim, JO; Shin, JH; Kim, ES; Jo, YK; Kim, JS; Park, SJ; Jin, DH; Hwang, JJ; Lee, SJ; Jeong, SY; Lee, C; Kim, I; Cho, DH				Park, Seong Ho; Park, So Jung; Kim, Joo-Oh; Shin, Ji Hyun; Kim, Eun Sung; Jo, Yoon Kyung; Kim, Jae-Sung; Park, So Jung; Jin, Dong-Hoon; Hwang, Jung Jin; Lee, Seung Jin; Jeong, Seong-Yun; Lee, Chaeyoung; Kim, InKi; Cho, Dong-Hyung			Down-Regulation of Survivin by Nemadipine-A Sensitizes Cancer Cells to TRAIL-Induced Apoptosis	BIOMOLECULES & THERAPEUTICS			English	Article						TRAIL; Nemadipine-A; Sensitization; Cell death; H1299 cells	COLON-CARCINOMA CELLS; HUMAN-MELANOMA CELLS; MEDIATED APOPTOSIS; UP-REGULATION; EXPRESSION; ACTIVATION; RESISTANCE; PATHWAY; LIGAND; INHIBITION	The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family of cytokines. TRAIL selectively induces apoptotic cell death in various tumors and cancer cells, but it has little or no toxicity in normal cells. Agonism of TRAIL receptors has been considered to be a valuable cancer-therapeutic strategy. However, more than 85% of primary tumors are resistant to TRAIL, emphasizing the importance of investigating how to overcome TRAIL resistance. In this report, we have found that nemadipine-A, a cell-permeable L-type calcium channel inhibitor, sensitizes TRAIL-resistant cancer cells to this ligand. Combination treatments using TRAIL with nemadipine-A synergistically induced both the caspase cascade and apoptotic cell death, which were blocked by a pan caspase inhibitor (zVAD) but not by autophagy or a necrosis inhibitor. We further found that nemadipine-A, either alone or in combination with TRAIL, notably reduced the expression of survivin, an inhibitor of the apoptosis protein (IAP) family of proteins. Depletion of survivin by small RNA interference (siRNA) resulted in increased cell death and caspase activation by TRAIL treatment. These results suggest that nemadipine-A potentiates TRAIL-induced apoptosis by down-regulation of survivin expression in TRAIL resistant cells. Thus, combination of TRAIL with nemadipine-A may serve a new therapeutic scheme for the treatment of TRAIL resistant cancer cells, suggesting that a detailed study of this combination would be useful.	[Park, Seong Ho] Hallym Univ, Ilsong Inst Life Sci, Anyang 431060, South Korea; [Park, So Jung; Kim, Joo-Oh; Shin, Ji Hyun; Kim, Eun Sung; Jo, Yoon Kyung; Cho, Dong-Hyung] Kyung Hee Univ, Grad Sch East West Med Sci, Yongin 446701, South Korea; [Kim, Jae-Sung] Korea Inst Radiol & Med Sci, Div Radiat Canc Res, Seoul 136706, South Korea; [Park, So Jung; Jin, Dong-Hoon; Hwang, Jung Jin; Lee, Seung Jin; Jeong, Seong-Yun; Kim, InKi] Asan Med Ctr, Asan Inst Life Sci, Seoul 138736, South Korea; [Jin, Dong-Hoon; Hwang, Jung Jin; Lee, Seung Jin; Jeong, Seong-Yun] Univ Ulsan, Coll Med, Asan Med Ctr, Inst Innovat Canc Res, Seoul 138736, South Korea; [Lee, Chaeyoung] Soongsil Univ, Dept Bioinformat & Life Sci, Seoul 156743, South Korea; [Kim, InKi] Univ Ulsan, Coll Med, Dept Med, Seoul 138736, South Korea		Kim, I (corresponding author), Asan Med Ctr, Asan Inst Life Sci, Seoul 138736, South Korea.	ik.kim@amc.seoul.kr; dhcho@khu.ac.kr	Lee, Chaeyoung/C-7929-2012; Hwang, Jung Jin/F-3424-2014	Lee, Chaeyoung/0000-0002-2940-1778; Lee, Seung Jin/0000-0003-0625-7774	Kyung Hee University [KHU-20101839]	This research was supported by a grant from Kyung Hee University in 2010 (KHU-20101839).	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Ther.	JAN 31	2013	21	1					29	34		10.4062/biomolther.2012.088			6	Biochemistry & Molecular Biology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy	284QK	WOS:000329334900004	24009855	Green Published, Bronze, Green Submitted			2022-04-25	
J	Ma, J; Liu, L; Ling, Y; Zheng, JH				Ma, Jian; Liu, Lei; Ling, Yang; Zheng, Jianhua			Polypeptide LTX-315 reverses the cisplatin chemoresistance of ovarian cancer cells via regulating Beclin-1/PI3K/mTOR signaling pathway	JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY			English	Article						autophagy; cisplatin chemoresistance; LTX-315; ovarian cacner	ONCOLYTIC PEPTIDE LTX-315; COLON-CANCER; AUTOPHAGY; RESISTANCE; TUMOR	Objective Polypeptide LTX-315 induces immunogenic cell death, thus having the potential to improve the effect of anticancer treatment. However, the function of LTX-315 in reversing chemoresistance in ovarian cancer (OC) still remains elusive. Our study aims to decipher the effect of LTX-315 on reversing the chemoresistance of OC cells and explore its mechanism. Methods SKOV3, A2780, SKOV3/DDP, and A2780/DDP cells (cisplatin [DDP]-resistant cells] were treated with different concentrations of LTX-315 (10 and 20 mu mol/L), respectively. Cell counting kit-8 assay, Transwell assay, and flow cytometry were used to assess cell viability, migration, invasion, apoptosis rate, and cell cycle of the cells. Western blot was performed to examine the expression of cleaved caspase 3, caspase 3, cleaved Poly (ADP-ribose) polymerase (PARP), PARP, Bax, Bcl-2, Beclin-1, p-Akt, Akt, p-mammalian target of rapamycin (mTOR), and mTOR. Furthermore, OC cells were treated with autophagy inhibitor 3-methyladenine (3-MA), and "rescue experiments" were performed. Results DDP-resistant OC cell models were established, and LTX-315 treatment resulted in lower IC50 of DDP. In OC cells treated with LTX-315, the viability, migration, invasion and the expression of Bcl-2 of were repressed, but the apoptotic rate and the expression of cleaved caspase 3, cleaved PARP and Bax were increased, and the cell cycle was arrested. Moreover, LTX-315 promoted Beclin-1 expression level and inhibited p-Akt and p-mTOR expression levels, whereas 3-MA could partially reverse the biological effects of LTX-315 on OC cells. Conclusion LTX-315 can inhibit the resistance of OC cells to DDP in vitro and plays a role by regulating Beclin-1/phosphatidylinositol-3-kinase/mTOR signaling pathway.	[Ma, Jian] Soochow Univ, Affiliated Hosp 3, Dept Med Oncol, Changzhou, Peoples R China; [Ma, Jian; Ling, Yang] Soochow Univ, Changzhou Tumor Hosp, Dept Med Oncol, Changzhou 213000, Jiangsu, Peoples R China; [Liu, Lei; Zheng, Jianhua] Harbin Med Univ, Clin Med Coll 1, Dept Obstet & Gynecol, Harbin, Peoples R China; [Liu, Lei] Harbin Med Univ, Affiliated Canc Hosp, Dept Obstet & Gynecol, Harbin, Peoples R China		Ling, Y (corresponding author), Soochow Univ, Changzhou Tumor Hosp, Dept Med Oncol, Changzhou 213000, Jiangsu, Peoples R China.; Zheng, JH (corresponding author), Harbin Med Univ, Clin Med Coll 1, 23 Youzheng St, Harbin 150001, Heilongjiang, Peoples R China.	2559512439@qq.com; kelanba5@163.com					Camilio KA, 2019, BREAST CANCER RES, V21, DOI 10.1186/s13058-018-1092-x; Gao J, 2019, BIOMED PHARMACOTHER, V120, DOI 10.1016/j.biopha.2019.109505; Ghoneum A, 2019, CANCERS, V11, DOI 10.3390/cancers11070949; Gu YF, 2020, ANTI-CANCER DRUG, V31, P385, DOI 10.1097/CAD.0000000000000886; Haybaeck J., 2020, CANCERS, V12; Jebsen NL, 2019, J MED CASE REP, V13, DOI 10.1186/s13256-019-2088-6; Jiang XY, 2019, J CANCER, V10, P1764, DOI 10.7150/jca.26481; Kim A, 2012, J EXP CLIN CANC RES, V31, DOI 10.1186/1756-9966-31-14; Li YC, 2019, ONCOTARGETS THER, V12, P2649, DOI 10.2147/OTT.S188054; Liang XH, 2001, CANCER RES, V61, P3443; Liao HW, 2019, CELL STRESS, V3, P348, DOI 10.15698/cst2019.11.204; Luan WQ, 2019, ONCOTARGETS THER, V12, P8063, DOI 10.2147/OTT.S220267; Ma SH, 2020, J CELL BIOCHEM, V121, P3256, DOI 10.1002/jcb.29593; Minamoto T, 2018, ONCOL LETT, V15, P1170, DOI 10.3892/ol.2017.7379; Muhammad N, 2017, ONCOTARGET, V8, P66226, DOI 10.18632/oncotarget.19887; Pilie PG, 2019, NAT REV CLIN ONCOL, V16, P81, DOI 10.1038/s41571-018-0114-z; Santa-Gonzalez GA, 2020, DATA BRIEF, V30, DOI 10.1016/j.dib.2020.105443; Si XQ, 2020, BIOMED PHARMACOTHER, V123, DOI 10.1016/j.biopha.2019.109717; Singh S, 2017, FEBS LETT, V591, P1371, DOI 10.1002/1873-3468.12655; Sun Yang, 2015, Asian Pac J Cancer Prev, V16, P2785; Yu Y, 2016, INT J ONCOL, V49, P285, DOI 10.3892/ijo.2016.3507; Zheng LM, 2020, GYNECOL ONCOL, V159, P239, DOI 10.1016/j.ygyno.2020.07.008; Zhou H, 2015, ONCOTARGET, V6, P26599, DOI 10.18632/oncotarget.5613; Zhou J, 2020, CELL PROLIFERAT, V53, DOI 10.1111/cpr.12739; Zou HX, 2019, EXP THER MED, V18, P4510, DOI 10.3892/etm.2019.8066	25	1	1	9	9	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1095-6670	1099-0461		J BIOCHEM MOL TOXIC	J. Biochem. Mol. Toxicol.	SEP	2021	35	9							e22853	10.1002/jbt.22853		JUL 2021	8	Biochemistry & Molecular Biology; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Toxicology	UQ0FH	WOS:000678805100001	34309113				2022-04-25	
J	de Franca, MNF; Isidorio, RG; Bonifacio, JHO; dos Santos, EWP; Santos, JF; Ottoni, FM; de Lucca, W; Scher, R; Alves, RJ; Correa, CB				Farias de Franca, Mariana Nobre; Isidorio, Raquel Geralda; Oliveira Bonifacio, Joao Henrique; Propheta dos Santos, Edmilson Willian; Santos, Jileno Ferreira; Ottoni, Flaviano Melo; de Lucca Junior, Waldecy; Scher, Ricardo; Alves, Ricardo Jose; Correa, Cristiane Bani			Anti-proliferative and pro-apoptotic activity of glycosidic derivatives of lawsone in melanoma cancer cell	BMC CANCER			English	Article						Lawsone; Melanoma; Cytotoxicity; Apoptosis; Flow cytometer; Migration; Clonogenic assay	MOLECULAR-MECHANISMS; COLON-CANCER; IN-VITRO; ASSAY; PROLIFERATION; THERAPEUTICS; CYTOTOXICITY; AUTOPHAGY	BackgroundMelanoma is a malignant cancer that affects melanocytes and is considered the most aggressive skin-type cancer. The prevalence for melanoma cancer for the last five year is about one million cases. The impact caused of this and other types of cancer, revel the importance of research into potential active compounds. The natural products are an important source of compounds with biological activity and research with natural products may enable the discovery of compounds with potential activity in tumor cells.MethodsThe Sulforhodamine B was used to determine cell density after treatment with lawsone derivatives. Apoptosis and necrosis were analyzed by flow cytometer. Morphological changes were observed by fluorescence using the Phalloidin/FITC and DAPI stains. The clonogenic and wound healing assays were used to analyze reduction of colonies formation and migratory capacity of melanoma cells, respectability.ResultsIn pharmacological screening, seven compounds derived from lawsone were considered to have high cytotoxic activity (GI>75%). Three compounds were selected to assess the inhibitory concentration for 50% of cells (IC50), and the compound 9, that has IC50 5.3 mu M in melanoma cells, was selected for further analyses in this cell line. The clonogenic assay showed that the compound is capable of reducing the formation of melanoma colonies at 10.6 mu M concentration. The compound induced apoptotic morphological changes in melanoma cells and increased by 50% the cells dying from apoptosis. Also, this compound reduced the migratory capacity of melanoma cells.ConclusionsThe results of this study showed that the evaluated lawsone derivatives have potential activity on tumor cells. The compound 9 is capable of inducing cell death by apoptosis in melanoma cells (B16F10).	[Farias de Franca, Mariana Nobre; Oliveira Bonifacio, Joao Henrique; Propheta dos Santos, Edmilson Willian; Santos, Jileno Ferreira; Scher, Ricardo; Correa, Cristiane Bani] Univ Fed Sergipe, Dept Morphol, Lab Biol & Immunol Canc & Leishmania, Sao Cristovao, Sergipe, Brazil; [Farias de Franca, Mariana Nobre; Propheta dos Santos, Edmilson Willian; Correa, Cristiane Bani] Univ Fed Sergipe, Grad Program Hlth Sci, Aracaju, Sergipe, Brazil; [Isidorio, Raquel Geralda; Ottoni, Flaviano Melo; Alves, Ricardo Jose] Univ Fed Minas Gerais, Fac Pharm, Dept Pharmaceut Prod, Lab Pharmaceut Chem, Belo Horizonte, MG, Brazil; [de Lucca Junior, Waldecy] Univ Fed Sergipe, Dept Morphol, Lab Mol Neurosci Sergipe, Sao Cristovao, Sergipe, Brazil		Correa, CB (corresponding author), Univ Fed Sergipe, Dept Morphol, Lab Biol & Immunol Canc & Leishmania, Sao Cristovao, Sergipe, Brazil.; Correa, CB (corresponding author), Univ Fed Sergipe, Grad Program Hlth Sci, Aracaju, Sergipe, Brazil.	crisbani@gmail.com	Correa, Cristiane Bani/AAR-9384-2020				Aminin D, 2020, CHEM PHARM BULL, V68, P46, DOI 10.1248/cpb.c19-00911; 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J	Xie, CM; Wei, DP; Zhao, LL; Marchetto, S; Mei, L; Borg, JP; Sun, Y				Xie, Chuan-Ming; Wei, Dongping; Zhao, Lili; Marchetto, Sylvie; Mei, Lin; Borg, Jean-Paul; Sun, Yi			Erbin is a novel substrate of the Sag-beta TrCP E3 ligase that regulates Kras(G12D)-induced skin tumorigenesis	JOURNAL OF CELL BIOLOGY			English	Article							COLON-CANCER CELLS; F-BOX PROTEIN; UBIQUITIN LIGASE; FUNCTIONAL-CHARACTERIZATION; ERBB2/HER2 RECEPTOR; KAPPA-B; K-RAS; AUTOPHAGY; DEGRADATION; SENESCENCE	SAG/RBX2 is the RING (really interesting new gene) component of Cullin-RING ligase, which is required for its activity. An organ-specific role of SAG in tumorigenesis is unknown. We recently showed that Sag/Rbx2, upon lung-targeted deletion, suppressed Kras(G12D)-induced tumorigenesis via inactivating NF-kappa B and mammalian target of rapamycin pathways. In contrast, we report here that, upon skin-targeted deletion, Sag significantly accelerated Kras(G12D)-induced papillomagenesis. In Kras(G12D)-expressing primary keratinocytes, Sag deletion promotes proliferation by inhibiting autophagy and senescence, by inactivating the Ras-Erk pathway, and by blocking reactive oxygen species (ROS) generation. This is achieved by accumulation of Erbin to block Ras activation of Raf and Nrf2 to scavenge ROS and can be rescued by knockdown of Nrf2 or Erbin. Simultaneous one-allele deletion of the Erbin-encoding gene Erbb2ip partially rescued the phenotypes. Finally, we characterized Erbin as a novel substrate of SAG-beta TrCP E3 ligase. By degrading Erbin and Nrf2, Sag activates the Ras-Raf pathway and causes ROS accumulation to trigger autophagy and senescence, eventually delaying Kras(G12D)-induced papillomagenesis and thus acting as a skin-specific tumor suppressor.	[Xie, Chuan-Ming; Wei, Dongping] Univ Michigan, Dept Radiat Oncol, Div Radiat & Canc Biol, Ann Arbor, MI 48109 USA; [Zhao, Lili] Univ Michigan, Dept Radiat Oncol, Dept Biostat, Ann Arbor, MI 48109 USA; [Sun, Yi] Zhejiang Univ, Sch Med, Inst Translat Med, Hangzhou 310058, Zhejiang, Peoples R China; [Sun, Yi] Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou 310058, Zhejiang, Peoples R China; [Marchetto, Sylvie; Borg, Jean-Paul] INSERM, U1068, Canc Res Ctr Marseille Cell Polar Cell Signalling, F-13009 Marseille, France; [Marchetto, Sylvie; Borg, Jean-Paul] Inst J Paoli I Calmettes, F-13009 Marseille, France; [Marchetto, Sylvie; Borg, Jean-Paul] Aix Marseille Univ, F-13284 Marseille, France; [Marchetto, Sylvie; Borg, Jean-Paul] CNRS, UMR7258, F-13009 Marseille, France; [Mei, Lin] Georgia Regents Univ, Dept Neurosci & Regenerat Med, Med Coll Georgia, Augusta, GA 30912 USA; [Mei, Lin] Georgia Regents Univ, Dept Neurol, Med Coll Georgia, Augusta, GA 30912 USA		Sun, Y (corresponding author), Univ Michigan, Dept Radiat Oncol, Div Radiat & Canc Biol, Ann Arbor, MI 48109 USA.	sunyi@umich.edu	Sun, Yi/K-1025-2014; Borg, Jean-Paul/AAX-8096-2020; Xie, Chuan-Ming/AAT-9557-2021	Sun, Yi/0000-0002-5841-4287; Borg, Jean-Paul/0000-0001-8418-3382; Xie, Chuan-Ming/0000-0003-4362-6612	National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA118762, CA156744, CA171277]; La Ligue Contre le Cancer (Label Ligue); Institut Paoli-Calmettes grants; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA156744, R01CA118762, R01CA171277, P30CA046592] Funding Source: NIH RePORTER	This work was supported by National Cancer Institute grants (CA118762, CA156744, and CA171277) to Y. Sun and by La Ligue Contre le Cancer (Label Ligue) and Institut Paoli-Calmettes grants to J.-P. Borg. J.-P. Borg is a member of Institut Universitaire de France.	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Cell Biol.	JUN 8	2015	209	5					721	737		10.1083/jcb.201411104			17	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	CK1AR	WOS:000355938200008	26056141	Bronze, Green Published, Green Submitted			2022-04-25	
J	Pellegrini, P; Serviss, JT; Lundback, T; Bancaro, N; Mazurkiewicz, M; Kolosenko, I; Yu, D; Haraldsson, M; D'Arcy, P; Linder, S; De Milito, A				Pellegrini, Paola; Serviss, Jason T.; Lundback, Thomas; Bancaro, Nicolo; Mazurkiewicz, Magdalena; Kolosenko, Iryna; Yu, Di; Haraldsson, Martin; D'Arcy, Padraig; Linder, Stig; De Milito, Angelo			A drug screening assay on cancer cells chronically adapted to acidosis	CANCER CELL INTERNATIONAL			English	Article						Tumor acidosis; Drug resistance; RNAseq; Verteporfin; Drug screening	VERTEPORFIN-PHOTODYNAMIC THERAPY; EXTRACELLULAR PH; MELANOMA-CELLS; TUMOR ACIDITY; RESISTANCE; AUTOPHAGY; LIGHT; PROLIFERATION; YAP	Background: Drug screening for the identification of compounds with anticancer activity is commonly performed using cell lines cultured under normal oxygen pressure and physiological pH. However, solid tumors are characterized by a microenvironment with limited access to nutrients, reduced oxygen supply and acidosis. Tumor hypoxia and acidosis have been identified as important drivers of malignant progression and contribute to multicellular resistance to different forms of therapy. Tumor acidosis represents an important mechanism mediating drug resistance thus the identification of drugs active on acid-adapted cells may improve the efficacy of cancer therapy. Methods: Here, we characterized human colon carcinoma cells (HCT116) chronically adapted to grow at pH 6.8 and used them to screen the Prestwick drug library for cytotoxic compounds. Analysis of gene expression profiles in parental and low pH-adapted cells showed several differences relating to cell cycle, metabolism and autophagy. Results: The screen led to the identification of several compounds which were further selected for their preferential cytotoxicity towards acid-adapted cells. Amongst 11 confirmed hits, we primarily focused our investigation on the benzoporphyrin derivative Verteporfin (VP). VP significantly reduced viability in low pH-adapted HCT116 cells as compared to parental HCT116 cells and normal immortalized epithelial cells. The cytotoxic activity of VP was enhanced by light activation and acidic pH culture conditions, likely via increased acid-dependent drug uptake. VP displayed the unique property to cause light-dependent cross-linking of proteins and resulted in accumulation of polyubiquitinated proteins without inducing inhibition of the proteasome. Conclusions: Our study provides an example and a tool to identify anticancer drugs targeting acid-adapted cancer cells.	[Pellegrini, Paola; Serviss, Jason T.; Bancaro, Nicolo; Mazurkiewicz, Magdalena; Kolosenko, Iryna; Yu, Di; De Milito, Angelo] Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, R8 00, S-17176 Stockholm, Sweden; [Lundback, Thomas; Haraldsson, Martin] Chem Biol Consortium Sweden, Sci Life Lab, Stockholm, Sweden; [D'Arcy, Padraig; Linder, Stig] Linkoping Univ, Dept Med & Hlth Sci, S-58183 Linkoping, Sweden; [Lundback, Thomas] AstraZeneca, IMED Biotech Unit, Discovery Sci, Gothenburg, Sweden		De Milito, A (corresponding author), Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, R8 00, S-17176 Stockholm, Sweden.	angelo.de-milito@ki.se	Lundbäck, Thomas/G-8076-2018; D'Arcy, Pádraig/F-7633-2018; D'Arcy, Pádraig/AAB-5045-2019	Lundbäck, Thomas/0000-0002-8145-7808; D'Arcy, Pádraig/0000-0001-6671-7600; D'Arcy, Pádraig/0000-0001-6671-7600; De Milito, Angelo/0000-0003-2591-2914; Serviss, Jason/0000-0002-5778-7014	Swedish Cancer SocietySwedish Cancer Society [CAN 2012/415]; Association for International Cancer Research [11-0522]; Robert Lundberg Foundation	This work was supported by Grants from the Swedish Cancer Society (Grant #CAN 2012/415), the Association for International Cancer Research (Grant #11-0522) and the Robert Lundberg Foundation.	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SEP 25	2018	18								147	10.1186/s12935-018-0645-5			15	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GV1GK	WOS:000445819100001	30263014	Green Published, gold			2022-04-25	
J	Kumari, M; Purohit, MP; Patnaik, S; Shukla, Y; Kumar, P; Gupta, KC				Kumari, Manisha; Purohit, Mahaveer Prasad; Patnaik, Satyakam; Shukla, Yogeshwer; Kumar, Pradeep; Gupta, Kailash Chand			Curcumin loaded selenium nanoparticles synergize the anticancer potential of doxorubicin contained in self-assembled, cell receptor targeted nanoparticles	EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS			English	Article						Doxorubicin; Nanoparticles; Selenium; Curcumin; Apoptosis; Ehrlich's ascites carcinoma	NF-KAPPA-B; EPITHELIAL-MESENCHYMAL TRANSITION; COLON-CANCER CELLS; DRUG-DELIVERY; TUMOR-CELLS; HYDROGEN-PEROXIDE; HYALURONIC-ACID; IN-VITRO; APOPTOSIS; MECHANISMS	Doxorubicin (DOX) has been extensively used to treat a wide range of cancers in free and nanotized form. Nanotization of DOX has alleviated its toxicity and efflux-mediated resistance. However, frequent upregulation of anti-apoptotic pathways, chemotherapy-enhanced inflammation, and epithelial-mesenchymal transition (EMT), present additional aspects of cellular DOX resistance. Nanoparticle-mediated combination therapy of DOX with additional anticancer agents is expected to offer greater therapeutic benefit by alleviating the overall drug resistance. We synthesized CD44-targeted DOX loaded nanoparticles (PSHA-DOXNPs) and evaluated their anticancer efficacy in combination with curcumin loaded selenium nanoparticles (Se-Cur NPs), previously developed by our group (Kumari et al., 2017). Combination of these nanoparticles (NPs) increased ROS level, decreased mitochondrial membrane potential, induced cell cycle arrest and apoptosis in HCT116 cells. This combination decreased the expressions of NF kappa B, Phospho-NF kappa B, EMT-metastasis-associated proteins (Snail, Vimentin, N-cadherin, CD44, MMP-2 and MMP-9), autophagy-associated proteins (Beclin-1 and LC-3BII), as well as anti-apoptotic protein Bcl-2, increased the expression of pro-apoptotic protein Bax, and increased cyt c release, which indicated decrease in inflammation, metastasis, and autophagy with increase in apoptosis. Moreover, the combination of NPs decreased tumor burden and increased survival of Ehrlich's ascites carcinoma (EAC)-bearing mice.	[Kumari, Manisha; Kumar, Pradeep; Gupta, Kailash Chand] CSIR Inst Genom & Integrat Biol, Delhi Univ Campus,Mall Rd, Delhi 110007, India; [Purohit, Mahaveer Prasad; Patnaik, Satyakam; Shukla, Yogeshwer] CSIR Indian Inst Toxicol Res, MG Marg, Lucknow 226001, Uttar Pradesh, India; [Kumari, Manisha; Purohit, Mahaveer Prasad] Acad Sci & Innovat Res AcSIR, New Delhi, India		Gupta, KC (corresponding author), CSIR Inst Genom & Integrat Biol, Delhi Univ Campus,Mall Rd, Delhi 110007, India.	kcgupta9@gmail.com	Kumari, Manisha/AAX-5517-2021; Patnaik, Satyakam/O-3617-2019	Patnaik, Satyakam/0000-0003-4920-236X; KUMAR, PRADEEP/0000-0001-5874-8191	CSIR network projectCouncil of Scientific & Industrial Research (CSIR) - India [BSC0112]; Indian Council of Medical Research (ICMR), New DelhiIndian Council of Medical Research (ICMR); CSIRCouncil of Scientific & Industrial Research (CSIR) - India	The authors gratefully acknowledge the financial support from CSIR network project BSC0112. KCG thanks, Indian Council of Medical Research (ICMR), New Delhi for awarding Dr. A.S. Paintal Distinguished Scientist Chair of ICMR. MK thanks CSIR for providing Senior Research Fellowship. Dr. P.N. Saxena, CSIR-IITR is acknowledged for helping in SEM studies. Mr. Jaishankar, CSIR-IITR and Ms. N. Arjaria, CSIR-IITR, are acknowledged for their help in TEM studies. Mr. Puneet Khare, CSIR-IITR is acknowledged for helping in flow cytometry-based experiments. Mr. S.H.N. Naqvi, CSIR-IITR is acknowledged for helping in animal studies.	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J. Pharm. Biopharm.	SEP	2018	130						185	199		10.1016/j.ejpb.2018.06.030			15	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	GQ6SN	WOS:000441855500020	29969665				2022-04-25	
J	Riedl, A; Schlederer, M; Pudelko, K; Stadler, M; Walter, S; Unterleuthner, D; Unger, C; Kramer, N; Hengstschlager, M; Kenner, L; Pfeiffer, D; Krupitza, G; Dolznig, H				Riedl, Angelika; Schlederer, Michaela; Pudelko, Karoline; Stadler, Mira; Walter, Stefanie; Unterleuthner, Daniela; Unger, Christine; Kramer, Nina; Hengstschlager, Markus; Kenner, Lukas; Pfeiffer, Dagmar; Krupitza, Georg; Dolznig, Helmut			Comparison of cancer cells in 2D vs 3D culture reveals differences in AKT-mTOR-S6K signaling and drug responses	JOURNAL OF CELL SCIENCE			English	Article						AKT-mTOR-S6K signaling; MAPK signaling; Spheroid; Drug response	TUMOR-CELLS; LINE CACO-2; MTOR; APOPTOSIS; MODELS; FIBROBLASTS; ACTIVATION; RESISTANCE; SPHEROIDS; AUTOPHAGY	Three-dimensional (3D) cancer models are used as preclinical systems to mimic physiologic drug responses. We provide evidence for strong changes of proliferation and metabolic capacity in three dimensions by systematically analyzing spheroids of colon cancer cell lines. Spheroids showed relative lower activities in the AKT, mammalian target of rapamycin (mTOR) and S6K (also known as RPS6KB1) signaling pathway compared to cells cultured in two dimensions. We identified spatial alterations in signaling, as the level of phosphorylated RPS6 decreased from the spheroid surface towards the center, which closely coordinated with the tumor areas around vessels in vivo. These 3D models displayed augmented antitumor responses to AKT-mTOR-S6K or mitogen-activated protein kinase (MAPK) pathway inhibition compared to those in 2D models. Inhibition of AKT-mTOR-S6K resulted in elevated ERK phosphorylation in 2D culture, whereas under these conditions, ERK signaling was reduced in spheroids. Inhibition of MEK1 (also known as MAP2K1) led to decreased AKT-mTOR-S6K signaling in 3D but not in 2D culture. These data indicate a distinct rewiring of signaling in 3D culture and during treatment. Detached tumor-cell clusters in vessels, in addition to circulating single tumor cells, play a putative role inmetastasis in human cancers. Hence, the understanding of signaling in spheroids and the responses in the 3D models upon drug treatment might be beneficial for anti-cancer therapies.	[Riedl, Angelika; Pudelko, Karoline; Stadler, Mira; Walter, Stefanie; Unterleuthner, Daniela; Unger, Christine; Kramer, Nina; Hengstschlager, Markus; Dolznig, Helmut] Med Univ Vienna, Inst Med Genet, Wahringer Str 10, A-1090 Vienna, Austria; [Schlederer, Michaela; Kenner, Lukas; Krupitza, Georg] Med Univ Vienna, Clin Inst Pathol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria; [Schlederer, Michaela; Kenner, Lukas] Ludwig Boltzmann Inst Canc Res, Wahringer Str 13A, A-1090 Vienna, Austria; [Kenner, Lukas] Univ Vet Med Vienna, UPLA, A-1210 Vienna, Austria; [Pfeiffer, Dagmar] Med Univ Graz, Inst Cell Biol Histol & Embryol, Harrachgasse 21, A-8010 Graz, Austria; [Riedl, Angelika] Boehringer Ingelheim RCV GmbH & Co KG, Dr Boehringer Gasse 5-11, A-1121 Vienna, Austria		Dolznig, H (corresponding author), Med Univ Vienna, Inst Med Genet, Wahringer Str 10, A-1090 Vienna, Austria.	helmut.dolznig@meduniwien.ac.at	Dolznig, Helmut/L-7005-2015	Dolznig, Helmut/0000-0002-6063-3585; Kenner, Lukas/0000-0003-2184-1338; Brislinger, Dagmar/0000-0002-7319-5377; Kramer, Nina/0000-0002-9058-8076; Krupitza, Georg/0000-0003-2949-7906	Niederosterreichische Forschungs- und Bildungsges.m.b.H (NFB); Austrian Academy of Sciences (OAW)	This work was supported by the Niederosterreichische Forschungs- und Bildungsges.m.b.H (NFB). A.R. was a recipient of a DOC fellowship from the Austrian Academy of Sciences (OAW).	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J	Bhol, CS; Panigrahi, DP; Praharaj, PP; Mahapatra, KK; Patra, S; Mishra, SR; Behera, BP; Bhutia, SK				Bhol, Chandra S.; Panigrahi, Debasna P.; Praharaj, Prakash P.; Mahapatra, Kewal K.; Patra, Srimanta; Mishra, Soumya R.; Behera, Bishnu P.; Bhutia, Sujit K.			Epigenetic modifications of autophagy in cancer and cancer therapeutics	SEMINARS IN CANCER BIOLOGY			English	Article						Autophagy; Epigenetics; Cancer; DNA methylation; Histone modification; miRNA	INCREASES DRUG-RESISTANCE; INDUCED DOWN-REGULATION; TUMOR-SUPPRESSOR; CELL-PROLIFERATION; GASTRIC-CANCER; INHIBITS AUTOPHAGY; DNA METHYLATION; HEPATOCELLULAR-CARCINOMA; ACTIVATING AUTOPHAGY; COLORECTAL-CANCER	Epigenetic alterations, such as DNA methylation, histone modifications and miRNAs, have a significant role play in malignant cellular transformation and metastasis. On the other hand, autophagy has been reported to perform context-dependent roles in cancer; at times, it becomes lethal and abolishes tumorigenesis, whereas, at other instances, it protects cancer cells by providing a rescue mechanism under adverse conditions. Although epigenetics and autophagy are two important and independent cellular processes, various oncogenic and oncosuppressor proteins involve autophagy through epigenetic modifications and different signaling pathways, thereby regulating tumor growth and therapeutic response. Moreover, the importance of epigenetic modification of autophagy in cancer is reflected through its involvement in cancer stem cell maintenance, which in turn, contributes to tumor cell viability during dormancy leading to tumor recurrence. The effects of epigenetic modifications of autophagy in cancer is still ambiguous and less acknowledged; therefore, efforts have been made to understand its detail underlying mechanism to unveil new targets and avenues for better prognosis and diagnosis of cancer.	[Bhol, Chandra S.; Panigrahi, Debasna P.; Praharaj, Prakash P.; Mahapatra, Kewal K.; Patra, Srimanta; Mishra, Soumya R.; Behera, Bishnu P.; Bhutia, Sujit K.] Natl Inst Technol Rourkela, Dept Life Sci, Canc & Cell Death Lab, Sundergarh, Odisha, India		Bhutia, SK (corresponding author), Natl Inst Technol Rourkela, Dept Life Sci, Canc & Cell Death Lab, Sundergarh, Odisha, India.	sujitb@nitrkl.ac.in	Bhol, Chandra Sekhar/W-6462-2019; Praharaj, Prakash P./J-5515-2018	Bhol, Chandra Sekhar/0000-0003-3397-6483; Praharaj, Prakash P./0000-0003-0425-5118; Patra, Srimanta/0000-0002-0166-0903; Behera, Bishnu Prasad/0000-0003-0326-6050	Government of India, Ministry of Human Resource DevelopmentMinistry of Human Resource Development (MHRD), Government of India; Board of Research in Nuclear Sciences (BRNS), Department of Atomic Energy (DAE)Department of Atomic Energy (DAE)Board of Research in Nuclear Sciences (BRNS) [37 (1)/14/38/2016-BRNS/37276]; Science and Engineering Research Board (SERB), Department of Science and Technology [EMR/2016/001246]	We thank National Institute of Technology Rourkela for providing the facility for this research work. CSB is obliged to Government of India, Ministry of Human Resource Development for providing fellowship. Research support was partly provided by the Board of Research in Nuclear Sciences (BRNS) [Number: 37 (1)/14/38/2016-BRNS/37276], Department of Atomic Energy (DAE); Science and Engineering Research Board (SERB) [Number: EMR/2016/001246], Department of Science and Technology. Moreover, the authors apologize to investigators whose original contributions have not been cited; we have chosen to cite recent publications in which details of such contributions can be found.	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J	Lenis-Rojas, OA; Fernandes, AR; Roma-Rodrigues, C; Baptista, PV; Marques, F; Perez-Fernandez, D; Guerra-Varela, J; Sanchez, L; Vazquez-Garcia, D; Torres, ML; Fernandez, A; Fernandez, JJ				Lenis-Rojas, O. A.; Fernandes, A. R.; Roma-Rodrigues, C.; Baptista, P. V.; Marques, F.; Perez-Fernandez, D.; Guerra-Varela, J.; Sanchez, L.; Vazquez-Garcia, D.; Lopez Torres, M.; Fernandez, A.; Fernandez, J. J.			Heteroleptic mononuclear compounds of ruthenium(II): synthesis, structural analyses, in vivo antitumor activity and in vivo toxicity on zebrafish embryost	DALTON TRANSACTIONS			English	Article							AUTOPHAGIC CELL-DEATH; POLYPYRIDYL COMPLEXES; DNA-BINDING; DEVELOPMENTAL TOXICITY; ANTICANCER ACTIVITY; MODEL SYSTEM; DRUG; PLATINUM; MECHANISMS; LIGANDS	The limitations of platinum complexes in cancer treatment have motivated the extensive investigation into other metal complexes such as ruthenium. We herein present the synthesis and characterization of a new family of ruthenium compounds 1a-5a with the general formula [Ru(bipy)(2)L][CF3SO3](2) (bipy = 2,2'-bipyridine; L = bidentate ligand: N,N; N,P; P,P; P,As) which have been characterized by elemental analysis, ES-MS, H-1 and P-31-{H-1} NMR, FTIR and conductivity measurements. The molecular structures of four Ru(II) complexes were determined by single crystal X-ray diffraction. All compounds displayed moderate cytotoxic activity in vitro against human A2780 ovarian, MCF7 breast and HCT116 colorectal tumor cells. Compound 5a was the most cytotoxic compound against A2780 and MCF7 tumor cells with an IC50 of 4.75 +/- 2.82 mu M and 20.02 +/- 1.46 mu M, respectively. The compounds showed no cytotoxic effect on normal human primary fibroblasts but rather considerable selectivity for A2780, MCF7 and HCT116 tumor cells. All compounds induce apoptosis and autophagy in A2780 ovarian carcinoma cells and some nuclear DNA fragmentation. All compounds interact with CT-DNA with intrinsic binding constants in the order 1a > 4a > 2a > 3a > 5a. The observed hyperchromic effect may be due to the electrostatic interaction between positively charged cations and the negatively charged phosphate backbone at the periphery of the double helix-CT-DNA. Interestingly, compound la shows a concentration dependent DNA double strand cleavage. In addition in vivo toxicity has been evaluated on zebrafish embryos unveiling the differential toxicity between the compounds, with LC50 ranging from 8.67 mg L-1 for compound la to 170.30 mg L-1 for compound 2a.	[Lenis-Rojas, O. A.; Vazquez-Garcia, D.; Lopez Torres, M.; Fernandez, A.; Fernandez, J. J.] Univ A Coruna, Dept Quim Fundamental, La Coruna 15008, Spain; [Lenis-Rojas, O. A.; Vazquez-Garcia, D.; Lopez Torres, M.; Fernandez, A.; Fernandez, J. J.] Univ A Coruna, CICA, La Coruna 15008, Spain; [Fernandes, A. R.; Roma-Rodrigues, C.; Baptista, P. V.] Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Ciencias Vida, UCIBIO, Campus Caparica, P-2829516 Caparica, Portugal; [Marques, F.] Univ Lisbon, Inst Super Tecn, C2TN, Estr Nacl 10 Km 139-7, P-2695066 Bobadela, Lrs, Portugal; [Perez-Fernandez, D.; Guerra-Varela, J.; Sanchez, L.] Univ Santiago de Compostela, Fac Vet, Dept Zool Genet & Antropol Fis, Lugo 27002, Spain		Fernandez, JJ (corresponding author), Univ A Coruna, Dept Quim Fundamental, La Coruna 15008, Spain.; Fernandez, JJ (corresponding author), Univ A Coruna, CICA, La Coruna 15008, Spain.; Fernandes, AR (corresponding author), Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Ciencias Vida, UCIBIO, Campus Caparica, P-2829516 Caparica, Portugal.	ma.fernandes@fct.unl.pt; lujjfs@udc.es	Digna, Vázquez García/L-6288-2014; Pérez-Fernández, David/D-3762-2017; Baptista, Pedro/P-3182-2019; López-Torres, Margarita/L-6072-2014; Fernández Sánchez, Jesús José/L-5960-2014; Roma-Rodrigues, Catarina/AAT-5658-2021; López, Alberto A. Fernández/L-6449-2014; Gómez, ACUIGEN/ABD-5337-2020; Rojas, Oscar/ABE-2206-2021; Sánchez, Laura/L-2411-2014; Roma-Rodrigues, Catarina/S-6144-2016; Marques, Fernanda M/J-9790-2013; Fernandes, Alexandra R/C-7465-2011	Digna, Vázquez García/0000-0002-2255-5651; Baptista, Pedro/0000-0001-5255-7095; López-Torres, Margarita/0000-0003-1288-5128; Fernández Sánchez, Jesús José/0000-0003-4938-0342; Roma-Rodrigues, Catarina/0000-0002-8676-6562; López, Alberto A. Fernández/0000-0003-2504-6016; Rojas, Oscar/0000-0002-5914-5787; Sánchez, Laura/0000-0001-7927-5303; Roma-Rodrigues, Catarina/0000-0002-8676-6562; Marques, Fernanda M/0000-0001-8440-5299; Fernandes, Alexandra R/0000-0003-2054-4438; Guerra-Varela, Jorge/0000-0002-8365-7125	Xunta de Galicia (Galicia, Spain) under the Grupos de Referencia Competitiva Programme [GRC2014/042]; Universidade da Coruna; Universidad de Santiago de Compostela [GRC2014/010]; Xunta de GaliciaXunta de GaliciaEuropean Commission [EM2014/056]; FCTPortuguese Foundation for Science and TechnologyEuropean Commission [UID/Multi/04349/2013]; FCT/MEC [UID/Multi/04378/2013]; ERDFEuropean Commission [POCI-01-0145-FEDER-007728]	This work was made possible thanks to the financial support received from the Xunta de Galicia (Galicia, Spain) under the Grupos de Referencia Competitiva Programme: Project GRC2014/042, Universidade da Coruna; and Project GRC2014/010, Universidad de Santiago de Compostela. DVG gratefully acknowledge the Xunta de Galicia support through EM2014/056 project. C2TN/IST author gratefully acknowledge the FCT support through UID/Multi/04349/2013 project. UCIBIO authors were financed by national funds from FCT/MEC (UID/Multi/04378/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728).	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DEC 21	2016	45	47					19127	19140		10.1039/c6dt03591d			14	Chemistry, Inorganic & Nuclear	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	EF1KE	WOS:000390082900039	27868117				2022-04-25	
J	Lee, MS; Kim, MS; Yoo, JK; Lee, JY; Ju, JE; Jeong, YK				Lee, Mi So; Kim, Mi-Sook; Yoo, Jae Kuk; Lee, Ji Young; Ju, Jae Eun; Jeong, Youn Kyoung			Enhanced anticancer effects of a mixture of low-dose mushrooms and Panax ginseng root extracts in human colorectal cancer cells	ONCOLOGY REPORTS			English	Article						anticancer effect; G2/M arrest; human colorectal cancer; mushroom; Panax ginseng; apoptosis; autophagy; DNA damage repair	PHELLINUS-LINTEUS; CYCLE ARREST; CORDYCEPS-MILITARIS; APOPTOSIS; POLYSACCHARIDE	Worldwide, colorectal cancer is the third most common cancer in men and the second most common in women. As conventional colorectal cancer therapies result in various side effects, there is a need for adjuvant therapy that can enhance the conventional therapies without complications. In this study, we investigated the anticancer effects of combined mixture of the several medicinal mushrooms and Panax ginseng root extracts (also called Amex7) as an adjuvant compound in the treatment of human colorectal cancer. We observed the in vivo inhibitory effect of Amex7 (1.25, 6.25, and 12.5 ml/kg, oral administration, twice daily) on tumor growth in a mouse model xenografted with HT-29 human colorectal cancer cells. In vitro, at 6, 12, and 24 h after 4% Amex7 treatment, we analyzed cell cycle by flow cytometry and the expression levels of cell cycle progression, apoptosis, and DNA damage repair-related proteins using immunoblotting and immunofluorescence staining in HT-29 cell line. As a result, Amex7 significantly suppressed tumor growth in HT-29 human colorectal cancer cells and xenografts. In vitro, Amex7 induced G2/M arrest through the regulation of cell cycle proteins and cell death by apoptosis and autophagy. Additionally, Amex7 consistently induced DNA damage and delayed the repair of Amex7-induced DNA damage by reducing the level of HR repair proteins. In conclusion, Amex7 enhanced anticancer effects through the induction of G2/M arrest and cell death, including apoptosis and autophagy. Furthermore, Amex7 impaired DNA damage repair. The present study provides a scientific rationale for the clinical use of a combined mixture of medicinal mushrooms and P. ginseng root extracts as an adjuvant treatment in human colorectal cancer.	[Lee, Mi So; Lee, Ji Young; Ju, Jae Eun; Jeong, Youn Kyoung] Korea Inst Radiol & Med Sci, Radiat Nonclin Ctr, 75 Nowon Ro, Seoul 01812, South Korea; [Kim, Mi-Sook] Korea Inst Radiol & Med Sci, Dept Radiat Oncol, 75 Nowon Ro, Seoul 01812, South Korea; [Yoo, Jae Kuk] Han Kook Shin Yak Pharmaceut Co Ltd, Nonsan 33023, South Korea		Jeong, YK (corresponding author), Korea Inst Radiol & Med Sci, Radiat Nonclin Ctr, 75 Nowon Ro, Seoul 01812, South Korea.; Kim, MS (corresponding author), Korea Inst Radiol & Med Sci, Dept Radiat Oncol, 75 Nowon Ro, Seoul 01812, South Korea.	mskim@kirams.re.kr; amy3523@kirams.re.kr			Korea Institute of Radiological and Medical Sciences (KIRAMS) - Ministry of Science, ICT and Future Planning, Republic of Korea [1711045548]	This study was supported by a grant of the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by Ministry of Science, ICT and Future Planning, Republic of Korea (no. 1711045548).	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Rep.	SEP	2017	38	3					1597	1604		10.3892/or.2017.5796			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	FB7CM	WOS:000406298700029	28714027	Bronze			2022-04-25	
J	Sklirou, A; Papanagnou, ED; Fokialakis, N; Trougakos, IP				Sklirou, Aimilia; Papanagnou, Eleni-Dimitra; Fokialakis, Nikolas; Trougakos, Ioannis P.			Cancer chemoprevention via activation of proteostatic modules	CANCER LETTERS			English	Review						Cancer prevention; Proteostasis network; Natural products; Nrf2; Chemopreventive agents	UNFOLDED PROTEIN RESPONSE; LIFE-SPAN; INCREASED SUSCEPTIBILITY; OXIDOREDUCTASE-1 DEFICIENCY; MOLECULAR CHAPERONES; COLON CARCINOGENESIS; PROTEASOME ACTIVITY; SIGNALING PATHWAYS; DIETARY CURCUMIN; MOUSE SKIN	Proteins carry out the majority of cellular functions and maintain cellular homeodynamics mostly by participating in multimeric assemblies that operate as protein machines. Proteome quality control is thus critical for cellular functionality, and it is carried out through the curating activity of the proteostasis network (PN). Key components of the PN are the protein synthesis and trafficking modules, the endoplasmic reticulum unfolded protein response, molecular chaperones, and the two main degradation machineries, namely the ubiquitin proteasome and autophagy lysosome pathways. Part of the PN are also several stress responsive pathways, including nuclear factor erythroid 2-related factor 2 (Nrf2), which mobilises genomic responses against oxidative and/or xenobiotic damage. Nevertheless, the gradual accumulation of stressors during ageing or earlier due to lifestyle results in an increasingly damaged and unstable proteome. This outcome may then increase genomic instability due to reduced DNA replication fidelity or repair, leading to various age-related diseases such as cancer. Considering that the activation of proteostatic modules exerts anti-ageing effects in model organisms, we present herein a synopsis of studies showing that proteostatic modules activation (e.g. by natural products) represents a promising tumour-chemopreventive approach. (C) 2017 Elsevier B.V. All rights reserved.	[Sklirou, Aimilia; Papanagnou, Eleni-Dimitra; Trougakos, Ioannis P.] Univ Athens, Dept Cell Biol & Biophys, Fac Biol, Panepistimiopolis, Athens 15784, Greece; [Fokialakis, Nikolas] Univ Athens, Dept Pharmacognosy & Nat Prod Chem, Fac Pharm, Athens 15771, Greece		Trougakos, IP (corresponding author), Univ Athens, Dept Cell Biol & Biophys, Fac Biol, Panepistimiopolis, Athens 15784, Greece.	itrougakos@biol.uoa.gr	Trougakos, Ioannis/R-6149-2018; Fokialakis, Nikolas/AAD-1498-2020	Trougakos, Ioannis/0000-0002-6179-2772; Fokialakis, Nikolas/0000-0001-7028-1870	EU grant TASCMAR (EU-H) [GA 634674]; EU grant MICROSMETICS (FP7-PEOPLE-IAPP) [GA 612276]	The authors apologise to those authors whose work was not cited due to space limitations. NF and IPT acknowledge funding from the EU grants TASCMAR (EU-H2020, GA 634674) and MICROSMETICS (FP7-PEOPLE-IAPP 2013, GA 612276).	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J	Nagakannan, P; Tabeshmehr, P; Eftekharpour, E				Nagakannan, Pandian; Tabeshmehr, Parisa; Eftekharpour, Eftekhar			Oxidative damage of lysosomes in regulated cell death systems: Pathophysiology and pharmacologic interventions	FREE RADICAL BIOLOGY AND MEDICINE			English	Article							AUTOPHAGY-DEPENDENT APOPTOSIS; COLON-CANCER CELLS; CASPASE-INDEPENDENT APOPTOSIS; CATHEPSIN-B CONTRIBUTES; ALPHA INDUCED APOPTOSIS; CYTOCHROME-C RELEASE; MEMBRANE PERMEABILIZATION; IN-VITRO; ACID SPHINGOMYELINASE; CYSTEINE CATHEPSINS	Lysosomes are small specialized organelles containing a variety of different hydrolase enzymes that are responsible for degradation of all macromolecules, entering the cells through the endosomal system or originated from the internal sources. This allows for transport and recycling of nutrients and internalization of surface proteins for antigen presentation as well as maintaining cellular homeostasis. Lysosomes are also important storage compartments for metal ions and nutrients. The integrity of lysosomal membrane is central to maintaining their normal function, but like other cellular membranes, lysosomal membrane is subject to damage mediated by reactive oxygen species. This results in spillage of lysosomal enzymes into the cytoplasm, leading to proteolytic damage to cellular systems and organelles. Several forms of lysosomal dependent cell death have been identified in diseases. Examination of these events are important for finding treatment strategies relevant to cancer or neurodegenerative diseases as well as autoimmune deficiencies. In this review, we have examined the current literature on involvement of lysosomes in induction of programed cell death and have provided an extensive list of therapeutic approaches that can modulate cell death. Exploitation of these mechanisms can lead to novel therapies for cancer and neurodegenerative diseases.	Univ Manitoba, Dept Physiol & Pathophysiol, Regenerat Med Program, Winnipeg, MB, Canada; Univ Manitoba, Dept Physiol & Pathophysiol, Spinal Cord Res Ctr, Winnipeg, MB, Canada		Eftekharpour, E (corresponding author), Univ Manitoba, 631-BMSB,745 Bannatyne Ave, Winnipeg, MB R3E 0J9, Canada.	eftekhar.eftekharpour@umanitoba.ca		Pandian, Nagakannan/0000-0002-6791-0661	Will-to-Win foundation - Wings for Life Foundation; Natural Sciences and Engineering Research Council of CanadaNatural Sciences and Engineering Research Council of Canada (NSERC)CGIAR	PN is supported by a studentship from Will-to-Win foundation. EE is currently funded by Wings for Life Foundation, and Natural Sciences and Engineering Research Council of Canada.	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Biol. Med.	SEP	2020	157				SI		94	127		10.1016/j.freeradbiomed.2020.04.001			34	Biochemistry & Molecular Biology; Endocrinology & Metabolism	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Endocrinology & Metabolism	NA9GR	WOS:000560125700009	32259579				2022-04-25	
J	Ashrafizadeh, M; Zarrabi, A; Orouei, S; Hushmandi, K; Hakimi, A; Zabolian, A; Daneshi, S; Samarghandian, S; Baradaran, B; Najafi, M				Ashrafizadeh, Milad; Zarrabi, Ali; Orouei, Sima; Hushmandi, Kiavash; Hakimi, Azadeh; Zabolian, Amirhossein; Daneshi, Salman; Samarghandian, Saeed; Baradaran, Behzad; Najafi, Masoud			MicroRNA-mediated autophagy regulation in cancer therapy: The role in chemoresistance/chemosensitivity	EUROPEAN JOURNAL OF PHARMACOLOGY			English	Review						MicroRNA; Autophagy; Chemoresistance; Chemosensitivity; Cancer therapy	EPITHELIAL-MESENCHYMAL TRANSITION; HYPOXIA-INDUCED AUTOPHAGY; HEPATOCELLULAR-CARCINOMA CELLS; CISPLATIN-INDUCED AUTOPHAGY; LUNG-CANCER; INHIBITING AUTOPHAGY; COLORECTAL-CANCER; OVARIAN-CANCER; GEMCITABINE RESISTANCE; DOWN-REGULATION	Chemoresistance has doubled the effort needed to reach an effective treatment for cancer. Now, scientists should consider molecular pathways and mechanisms involved in chemoresistance to overcome cancer. Autophagy is a "self-digestion" mechanism in which potentially toxic and aged organelles and macromolecules are degraded. Increasing evidence has shown that autophagy possesses dual role in cancer cells (onco-suppressor or oncogene). So, it is vital to identify its role in cancer progression and malignancy. MicroRNAs (miRs) are epigenetic factors capable of modulation of autophagy in cancer cells. In the current review, we emphasize on the relationship between miRs and autophagy in cancer chemotherapy. Besides, we discuss upstream mediators of miR/autophagy axis in cancer chemotherapy including long non-coding RNAs, circular RNAs, Nrf2 c-Myc, and HIF-1 alpha. At the final section, we provide a discussion about how anti-tumor compounds affect miR/autophagy axis in ensuring chemosensitivity. These topics are described in this review to show how autophagy inhibition/induction can lead to chemosensitivity/chemoresistance, and miRs are considered as key players in these discussions.	[Ashrafizadeh, Milad] Univ Tabriz, Fac Vet Med, Tabriz, Iran; [Zarrabi, Ali] Sabanci Univ, Nanotechnol Res & Applicat Ctr SUNUM, TR-34956 Istanbul, Turkey; [Orouei, Sima] Islamic Azad Univ, Dept Genet, Tehran Med Sci, Tehran, Iran; [Hushmandi, Kiavash] Univ Tehran, Fac Vet Med, Div Epidemiol & Zoonoses, Dept Food Hyg & Qual Control, Tehran, Iran; [Hakimi, Azadeh] Shiraz Univ Med Sci, Student Res Comm, Sch Med, Dept Anat Sci, Shiraz, Iran; [Zabolian, Amirhossein] Islamic Azad Univ, Tehran Med Sci, Young Researchers & Elite Club, Tehran, Iran; [Daneshi, Salman] Jiroft Univ Med Sci, Sch Hlth, Dept Publ Hlth, Jiroft, Iran; [Samarghandian, Saeed] Neyshabur Univ Med Sci, Dept Basic Med Sci, Neyshabur, Iran; [Baradaran, Behzad] Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz, Iran; [Najafi, Masoud] Kermanshah Univ Med Sci, Inst Hlth Technol, Med Technol Res Ctr, Kermanshah, Iran; [Najafi, Masoud] Kermanshah Univ Med Sci, Sch Paramed Sci, Radiol & Nucl Med Dept, Kermanshah, Iran		Baradaran, B (corresponding author), Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz, Iran.; Najafi, M (corresponding author), Kermanshah Univ Med Sci, Inst Hlth Technol, Med Technol Res Ctr, Kermanshah, Iran.	baradaranb@tbzmed.ac.ir; najafi_ma@yahoo.com	Baradaran, Behzad/AAQ-5177-2020; najafi, masoud/L-8434-2019; Zarrabi, Ali/U-2602-2019	Baradaran, Behzad/0000-0002-8642-6795; najafi, masoud/0000-0002-6341-9007; Zarrabi, Ali/0000-0003-0391-1769			Aali M, 2020, GENE, V757, DOI 10.1016/j.gene.2020.144936; Abolghasemi M, 2020, J CELL PHYSIOL, V235, P5008, DOI 10.1002/jcp.29396; Abolghasemi M, 2020, J CELL PHYSIOL, V235, P5059, DOI 10.1002/jcp.29442; Alvarez-Garcia V, 2019, SEMIN CANCER BIOL, V59, P66, DOI 10.1016/j.semcancer.2019.02.001; Alzahrani AS, 2019, SEMIN CANCER BIOL, V59, P125, DOI 10.1016/j.semcancer.2019.07.009; An Y, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2015.123; Axe EL, 2008, J CELL BIOL, V182, P685, DOI 10.1083/jcb.200803137; Babiarz JE, 2008, GENE DEV, V22, P2773, DOI 10.1101/gad.1705308; Bao L, 2016, DNA CELL BIOL, V35, P385, DOI 10.1089/dna.2016.3259; Bartel DP, 2004, CELL, V116, P281, DOI 10.1016/S0092-8674(04)00045-5; 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J. Pharmacol.	FEB 5	2021	892								173660	10.1016/j.ejphar.2020.173660			16	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	PQ8NJ	WOS:000606799900001	33310181		Y	N	2022-04-25	
J	Hu, WY; Hu, DP; Xie, LS; Li, Y; Majumdar, S; Nonn, L; Hu, H; Shioda, T; Prins, GS				Hu, Wen-Yang; Hu, Dan-Ping; Xie, Lishi; Li, Ye; Majumdar, Shyama; Nonn, Larisa; Hu, Hong; Shioda, Toshi; Prins, Gail S.			Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution	STEM CELL RESEARCH			English	Article						Prostate Stem cell; Progenitor cell; Prostasphere; Prostate cancer	PROGENITOR CELLS; SELF-RENEWAL; CANCER; BASAL; IDENTIFICATION; LINEAGE; FATE; MAINTENANCE; HOMEOSTASIS; EXPRESSION	Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/ asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-.B signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolismin stemcells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. (C) 2017 The Authors. Published by Elsevier B.V.	[Hu, Wen-Yang; Hu, Dan-Ping; Xie, Lishi; Li, Ye; Majumdar, Shyama; Prins, Gail S.] Univ Illinois, Coll Med, Dept Urol, Chicago, IL 60612 USA; [Nonn, Larisa; Prins, Gail S.] Univ Illinois, Coll Med, Dept Pathol, Chicago, IL 60612 USA; [Nonn, Larisa; Prins, Gail S.] Univ Illinois, Coll Med, Ctr Canc, Chicago, IL 60612 USA; [Hu, Hong] Univ Illinois, Res Resources Ctr, Chicago, IL 60612 USA; [Shioda, Toshi] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA; [Shioda, Toshi] Harvard Med Sch, Charlestown, MA 02129 USA		Prins, GS (corresponding author), Univ Illinois, Dept Urol, 820 South Wood St,M-C 955, Chicago, IL USA.	gprins@uic.edu	HU, WENYANG/L-2026-2019; Xie, Lishi/C-2334-2019	Xie, Lishi/0000-0003-2376-6685; Prins, Gail/0000-0002-9044-4734	National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01-CA172220, R01-ES02207, R01CA166588]; Michael Reese Research and Education Foundation; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA172220, R01CA166588] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [P30ES027792, R01ES022071] Funding Source: NIH RePORTER	This study was supported by grants from the National Cancer Institute R01-CA172220 (GSP, WYH, LN), R01-ES02207 (GSP, WYH), R01CA166588, (LN, GSP), and the Michael Reese Research and Education Foundation (GSP, WYH, TS). The authors wish to thank the services of the University of Illinois/ Chicago (UIC) Biorepository, Dr. Mark Maienschein-Cline for assistance with bioinformatics analysis, Dr. Alan M. Diamond for providing HCT116 cells, Dr. Marcelo G. Bonini for assistancewith Seahorse mito-stress assay, Dr. Susan Kasper, Dr. Hung-Ming Lam and Lynn Birch for assistance in the editing of the manuscript.	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J	Pal, RR; Rajpal, V; Singh, P; Saraf, SA				Pal, Ravi Raj; Rajpal, Vasundhara; Singh, Priya; Saraf, Shubhini A.			Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis	PHARMACEUTICS			English	Review						thymoquinone; cancer; arthritis; nanotechnology; synovial delivery; toxicity reduction	NIGELLA-SATIVA L.; EPITHELIAL-MESENCHYMAL TRANSITION; NEGATIVE BREAST-CANCER; COLON-CANCER; IN-VITRO; ANTICANCER ACTIVITY; ANTIINFLAMMATORY PROPERTIES; SIGNALING PATHWAYS; PLGA NANOPARTICLES; CELL CARCINOMA	Cancer causes a considerable amount of mortality in the world, while arthritis is an immunological dysregulation with multifactorial pathogenesis including genetic and environmental defects. Both conditions have inflammation as a part of their pathogenesis. Resistance to anticancer and disease-modifying antirheumatic drugs (DMARDs) happens frequently through the generation of energy-dependent transporters, which lead to the expulsion of cellular drug contents. Thymoquinone (TQ) is a bioactive molecule with anticancer as well as anti-inflammatory activities via the downregulation of several chemokines and cytokines. Nevertheless, the pharmacological importance and therapeutic feasibility of thymoquinone are underutilized due to intrinsic pharmacokinetics, including short half-life, inadequate biological stability, poor aqueous solubility, and low bioavailability. Owing to these pharmacokinetic limitations of TQ, nanoformulations have gained remarkable attention in recent years. Therefore, this compilation intends to critically analyze recent advancements in rheumatoid arthritis and cancer delivery of TQ. This literature search revealed that nanocarriers exhibit potential results in achieving targetability, maximizing drug internalization, as well as enhancing the anti-inflammatory and anticancer efficacy of TQ. Additionally, TQ-NPs (thymoquinone nanoparticles) as a therapeutic payload modulated autophagy as well as enhanced the potential of other drugs when given in combination. Moreover, nanoformulations improved pharmacokinetics, drug deposition, using EPR (enhanced permeability and retention) and receptor-mediated delivery, and enhanced anti-inflammatory and anticancer properties. TQ's potential to reduce metal toxicity, its clinical trials and patents have also been discussed.	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J	Li, X; Chen, FY; Kang, JW; Zhou, J; Peng, C; Huang, W; Zhou, MK; He, G; Han, B				Li, Xiang; Chen, Fei-Yu; Kang, Jing-Wen; Zhou, Jin; Peng, Cheng; Huang, Wei; Zhou, Mu-Ke; He, Gu; Han, Bo			Stereoselective Assembly of Multifunctional Spirocyclohexene Pyrazolones That Induce Autophagy-Dependent Apoptosis in Colorectal Cancer Cells	JOURNAL OF ORGANIC CHEMISTRY			English	Article							ORGANOCATALYTIC ASYMMETRIC-SYNTHESIS; CATALYZED 4+2 CYCLOADDITION; ENANTIOSELECTIVE SYNTHESIS; CASCADE REACTION; UNSATURATED PYRAZOLONES; ANTIMICROBIAL ACTIVITY; CONSTRUCTION; SCAFFOLD; SPIROPYRAZOLONES; PROLIFERATION	Enantio- and diastereoselective synthesis of multifunctional spiropyrazolone scaffolds has been achieved using secondary amine-catalyzed [4 + 2] annulations of alpha,beta,gamma,delta,-unsaturated pyrazolones with aldehydes. The pyrazolone substrates serve as C4 synthons to produce 6-membered, carbocycle-based, chiral spiropyrazolone derivatives. The synthesized chiral compounds showed potent toxicity against a panel of cancer cell lines. The most potent compound 3h-induced cell cycle arrest and macroautophagy in HCT116 colorectal cancer cells, triggering autophagy-dependent apoptotic cell death.	[Li, Xiang; Chen, Fei-Yu; Kang, Jing-Wen; Zhou, Jin; Peng, Cheng; Huang, Wei; Han, Bo] Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Sichuan, Peoples R China; [Zhou, Mu-Ke; He, Gu] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China; [Zhou, Mu-Ke; He, Gu] Sichuan Univ, West China Hosp, Dept Dermatol, Chengdu 610041, Sichuan, Peoples R China; [Zhou, Mu-Ke; He, Gu] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China		Peng, C; Han, B (corresponding author), Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Sichuan, Peoples R China.; He, G (corresponding author), Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China.; He, G (corresponding author), Sichuan Univ, West China Hosp, Dept Dermatol, Chengdu 610041, Sichuan, Peoples R China.; He, G (corresponding author), Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China.	pengcheng@cdutcm.edu.cn; hegu@scu.edu.cn; hanbo@cdutcm.edu.cn	He, Gu/G-5446-2015	He, Gu/0000-0002-1536-8882; Han, Bo/0000-0003-3200-4682	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81573588, 81773889, 21772131]; Science & Technology Department of Sichuan Province [2017JZYD0001, 2017JQ0002, 2017JY0323]	We are grateful for financial support from the National Natural Science Foundation of China (81573588, 81773889, and 21772131) and the Science & Technology Department of Sichuan Province (2017JZYD0001, 2017JQ0002, and 2017JY0323).	Alba ANR, 2011, EUR J ORG CHEM, V2011, P1318, DOI 10.1002/ejoc.201001452; Amata E, 2015, TETRAHEDRON LETT, V56, P2832, DOI 10.1016/j.tetlet.2015.04.061; Amireddy M, 2016, RSC ADV, V6, P77474, DOI 10.1039/c6ra13923j; Bondock S, 2008, EUR J MED CHEM, V43, P2122, DOI 10.1016/j.ejmech.2007.12.009; Chande MS, 2007, J HETEROCYCLIC CHEM, V44, P49, DOI 10.1002/jhet.5570440108; Chauhan P, 2015, CHEM COMMUN, V51, P12890, DOI 10.1039/c5cc04930j; Chauhan P, 2014, ORG LETT, V16, P2954, DOI 10.1021/ol501093v; Companyo X, 2010, CHEM COMMUN, V46, P6953, DOI 10.1039/c0cc01522a; Ding AS, 2018, CHEM SOC REV, V47, P5946, DOI 10.1039/c6cs00825a; Fustero S, 2011, CHEM REV, V111, P6984, DOI 10.1021/cr2000459; Han B, 2015, ADV SYNTH CATAL, V357, P561, DOI 10.1002/adsc.201400764; Horton DA, 2003, CHEM REV, V103, P893, DOI 10.1021/cr020033s; Hu MJ, 2017, MOL CELL, V66, P141, DOI 10.1016/j.molcel.2017.03.008; Ke BW, 2016, MED RES REV, V36, P983, DOI 10.1002/med.21398; Leng HJ, 2018, ADV SYNTH CATAL, V360, P229, DOI 10.1002/adsc.201701035; Leng HJ, 2015, CHEM-EUR J, V21, P18100, DOI 10.1002/chem.201503063; Li JH, 2016, ORG CHEM FRONT, V3, P1087, DOI 10.1039/c6qo00208k; Li JH, 2014, CHEM-ASIAN J, V9, P3278, DOI 10.1002/asia.201402706; Li JL, 2012, ACCOUNTS CHEM RES, V45, P1491, DOI 10.1021/ar3000822; Li Q, 2018, ANGEW CHEM INT EDIT, V57, P1913, DOI 10.1002/anie.201711813; Li X, 2018, EUR J ORG CHEM, V2018, P4723, DOI 10.1002/ejoc.201800710; Liang JY, 2013, ORG BIOMOL CHEM, V11, P1441, DOI 10.1039/c2ob27095a; Lipinski CA, 2001, ADV DRUG DELIVER REV, V46, P3, DOI 10.1016/S0169-409X(00)00129-0; Lipinski Christopher A, 2004, Drug Discov Today Technol, V1, P337, DOI 10.1016/j.ddtec.2004.11.007; Liu JY, 2017, ORG LETT, V19, P1846, DOI 10.1021/acs.orglett.7b00610; Liu SY, 2018, CHEM COMMUN, V54, P11515, DOI 10.1039/c8cc06196c; Mandha SR, 2012, BIOORG MED CHEM LETT, V22, P5272, DOI 10.1016/j.bmcl.2012.06.055; Meazza M, 2018, CHEM SCI, V9, P6368, DOI 10.1039/c8sc00913a; Melchiorre P, 2008, ANGEW CHEM INT EDIT, V47, P6138, DOI 10.1002/anie.200705523; Mokarram P, 2017, AUTOPHAGY, V13, P781, DOI 10.1080/15548627.2017.1290751; Mondal S, 2017, ORG LETT, V19, P4367, DOI 10.1021/acs.orglett.7b02085; Moyano A, 2011, CHEM REV, V111, P4703, DOI 10.1021/cr100348t; Mukherjee S, 2007, CHEM REV, V107, P5471, DOI 10.1021/cr0684016; Oh S, 2011, CHEM COMMUN, V47, P12754, DOI 10.1039/c1cc14042f; Putatunda S, 2019, CHEM SCI, V10, P4107, DOI 10.1039/c8sc05258a; Schmidt A, 2011, CURR ORG CHEM, V15, P1423, DOI 10.2174/138527211795378263; Sun P, 2014, TETRAHEDRON, V70, P9330, DOI 10.1016/j.tet.2014.10.038; Sun W, 2017, COATINGS, V7, DOI 10.3390/coatings7020032; Valero G, 2011, CHEM-EUR J, V17, P2018, DOI 10.1002/chem.201001546; Varvounis G., 2009, PYRAZOL 3 ONES 4; Wu B, 2012, EUR J ORG CHEM, V2012, P1318, DOI 10.1002/ejoc.201101529; Wu SC, 2016, EUR J MED CHEM, V115, P141, DOI 10.1016/j.ejmech.2016.03.039; Xie X, 2018, ADV SYNTH CATAL, V360, P194, DOI 10.1002/adsc.201700927; Xie X, 2012, CHEM COMMUN, V48, P10487, DOI 10.1039/c2cc36011j; Yang MC, 2017, ORG LETT, V19, P6752, DOI 10.1021/acs.orglett.7b03516; Yang WJ, 2015, RSC ADV, V5, P62343, DOI 10.1039/c5ra11595g; Yetra SR, 2016, ANGEW CHEM INT EDIT, V55, P268, DOI 10.1002/anie.201507802; Zea A, 2011, ORG BIOMOL CHEM, V9, P6519, DOI 10.1039/c1ob05753g; Zhang JX, 2013, ADV SYNTH CATAL, V355, P797, DOI 10.1002/adsc.201200925; Zhang YQ, 2015, EUR J ORG CHEM, V2015, P2030, DOI 10.1002/ejoc.201403673; Zhang YH, 2018, ORG CHEM FRONT, V5, P2229, DOI 10.1039/c8qo00422f; Zhao Q, 2018, CHEM COMMUN, V54, P8359, DOI 10.1039/c8cc04732d; Zheng L, 2015, RSC ADV, V5, P40007, DOI 10.1039/c5ra04698j; Zheng WP, 2015, RSC ADV, V5, P91108, DOI 10.1039/c5ra17792h; Zhou R, 2015, CHEM COMMUN, V51, P13113, DOI 10.1039/c5cc04968g	55	17	17	5	48	AMER CHEMICAL SOC	WASHINGTON	1155 16TH ST, NW, WASHINGTON, DC 20036 USA	0022-3263	1520-6904		J ORG CHEM	J. Org. Chem.	JUL 19	2019	84	14					9138	9150		10.1021/acs.joc.9b01098			13	Chemistry, Organic	Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC); Current Chemical Reactions (CCR-EXPANDED)	Chemistry	IK9ZY	WOS:000476957000030	31267754				2022-04-25	
J	Chatterjee, I; Zhang, YG; Zhang, JL; Lu, R; Xia, YL; Sun, J				Chatterjee, Ishita; Zhang, Yongguo; Zhang, Jilei; Lu, Rong; Xia, Yinglin; Sun, Jun			Overexpression of Vitamin D Receptor in Intestinal Epithelia Protects Against Colitis via Upregulating Tight Junction Protein Claudin 15	JOURNAL OF CROHNS & COLITIS			English	Article						Claudin; Crohn's disease; colonoids; IBD; inflammation; Salmonella; tight junction; VDR; ulcerative colitis	INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; GUT; EXPRESSION; LEADS; ACTIVATION; DEFECTS; PATHWAY; BARRIER; CANCER	Background and Aims: Dysfunction of the vitamin D receptor [VDR] contributes to the aetiology of IBD by regulating autophagy, immune response, and mucosal permeability. VDR directly controls the paracellular tight junction protein Claudin-2. Claudin-2 and Claudin-15 are unique in maintaining paracellular permeability. Interestingly, claudin-15 mRNA was downregulated in patients with ulcerative colitis. However, the exact mechanism of Claudin-15 regulation in colitis is still unknown. Here, we investigated the protective role of VDR against intestinal inflammation via upregulating Claudin-15. Methods: We analysed the correlation of Claudin-15 with the reduction of VDR in human colitis. We generated intestinal epithelial overexpression of VDR [O-VDR] mice to study the gain of function of VDR in colitis. Intestinal epithelial VDR knockout [VDRIEC] mice were used for the loss of function study. Colonoids and SKCO15 cells were used as in vitro models. Results: Reduced Claudin-15 was significantly correlated with decreased VDR along the colonic epithelium of human IBD. O-VDR mice showed decreased susceptibility to chemically and bacterially induced colitis and marked increased Claudin-15 expression [both mRNA and protein] in the colon. Correspondingly, colonic Claudin-15 was reduced in VDRIEC mice, which were susceptible to colitis. Overexpression of intestinal epithelial VDR and vitamin D treatment resulted in a significantly increased Claudin-15. ChIP assays identified the direct binding of VDR to the claudin-15 promoter, suggesting that claudin-15 is a target gene of VDR. Conclusion: We demonstrated the mechanism of VDR upregulation of Claudin-15 to protect against colitis. This might enlighten the mechanism of barrier dysfunction in IBD and potential therapeutic strategies to inhibit inflammation.	[Chatterjee, Ishita; Zhang, Yongguo; Zhang, Jilei; Lu, Rong; Xia, Yinglin; Sun, Jun] Univ Illinois, Dept Med, Div Gastroenterol & Hepatol, 840 S Wood St,Room 704 CSB,MC716, Chicago, IL 60612 USA; [Sun, Jun] Univ Illinois, UIC Canc Ctr, Chicago, IL USA; [Sun, Jun] Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60680 USA; [Sun, Jun] Jesse Brown VA Med Ctr, Chicago, IL USA		Sun, J (corresponding author), Univ Illinois, Dept Med, Div Gastroenterol & Hepatol, 840 S Wood St,Room 704 CSB,MC716, Chicago, IL 60612 USA.	junsun@uic.edu	Sun, Jun/S-7440-2019	Sun, Jun/0000-0001-7465-3133	NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01 DK105118, R01DK114126]; DOD (The Department of Defense) CDMRP (Congressionally Directed Medical Research Programs) [BC160450P1]; VA (Veterans Affairs) Merit Award [1 I01BX004824-01]	This work was supported by the NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) grant R01 DK105118, R01DK114126, and DOD (The Department of Defense) CDMRP (Congressionally Directed Medical Research Programs) log No BC160450P1, and the VA (Veterans Affairs) Merit Award 1 I01BX004824-01to JS (Prof. Jun Sun). The contents do not represent the views of the United States Department of Veterans Affairs or the United States Government.	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Crohns Colitis	OCT	2021	15	10					1720	1736		10.1093/ecco-jcc/jjab044		MAR 2021	17	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	WM9IT	WOS:000711392000011	33690841	Green Published			2022-04-25	
J	Zhong, WW; Dai, QQ; Huang, QH				Zhong, Weiwei; Dai, Qianqian; Huang, Qionghui			Effect of lncRNA KCNQ1OT1 on autophagy and drug resistance of hepatocellular carcinoma cells by targeting miR-338-3p	CELLULAR AND MOLECULAR BIOLOGY			English	Article						Hepatocellular carcinoma; lncRNA KCNQ1OT1; miR-338-3p; Survival rate; Autophagy; Cisplatin sensitivity	CANCER CELLS; COLON-CANCER	The current experiment aimed to investigate the effects of lncRNA KCNQ1OT1 on the proliferation, autophagy and drug resistance of hepatocellular carcinoma cells, as well as the potential molecular mechanism. Hepatocellular carcinoma SK-HEP-1 cells and DDP resistant SK-HEP-1/DDP cells were treated with cisplatin (DDP) of different concentrations (1 nmol/L 2 nmol/L, 4 nmol/L, 8 nmol/L, 16 nmol/L,). The survival rate 01 SK-HEP-1 and SK-HEP-TDDP cells vas determined by the CCK8 method. QRT-PCR was used to detect the levels of lncRNAKCNQ1OT1 and miR-338-3p in normal hepatocyte HH01, hepatocellular ell SK-HEP-1 and hepatoma cisplatin-resistant cell SK-HEP-1/DDP. Western blot was carried out to detect the expression levels of autophagy-related protein Beclin1 and proliferation-related protein P21 in cells. A dual-luciferase reporter assay system was performed to validate the relationship between KCNQ1OT1 and miR-338-3p. After the treatment of 1 nmol/L, 2 nmol/L, 8nmol/L, and 16nmol/L cisplatin (DDP), the survival rate or SK-HEP-FDDP cells is higher than that of SK-HEP-1 cells. The level or lncRNA KCNQ1OT1 was increased successively in HH01, SK-HEP-1 and SK-HEP-1/DDP cells, while miR-338-3p was decreased successively. Silencing lncRNA KCNQ1OT1 or over-expressing miR-338-3p combined with 16 nmol/L DDP treatment reduced the survival rate of SK-HEP-1/DDP cells and up-regulate levels of P21 and Beclin1 proteins. LncRNA KCNQ1OT1 targeted and negatively regulated the expression of miR-338-3p. Inhibition or miR-338-3p reversed the effect of silencing lncRNA KCNQ1OT1 on survival, autophagy and cisplatin sensitivity of SK-HEP-1/DDP cell. LncRNA KCNQ1OT1 targets miR-338-3p to regulate the survival rate and autophagy or SK-HEP-1/DDP cells and improve the cisplatin sensitivity of SK-HEP-1/DDP cells. LncRNA KCNQ1OT1 is a potential molecular target for hepatocellular carcinoma.	[Zhong, Weiwei] Jingmen 1 Peoples Hosp, GI Med, Jingmen 448000, Peoples R China; [Dai, Qianqian] Jingmen 1 Peoples Hosp, Infect Dis Dept, Jingmen 448000, Peoples R China; [Huang, Qionghui] Jingmen 2 Peoples Hosp, Psychiat Dept, Jingmen 448000, Peoples R China		Dai, QQ (corresponding author), Jingmen 1 Peoples Hosp, Infect Dis Dept, Jingmen 448000, Peoples R China.	dq_1005@126.com					Bordbar M, 2020, MODERN GENETICS, V15, P75; Dou Chunging, 2017, PROGR MODERN BIOMEDI, V17, P2290; Galluzzi L, 2015, EMBO J, V34, P856, DOI 10.15252/embj.201490784; Guan Wencai, 2018, CHIN HEPATOL, V23, P543; Han J, 2017, EXP CELL RES, V360, P328, DOI 10.1016/j.yexcr.2017.09.023; hi Jun, 2012, PROGR PHYSL SCI, V43, P77; Hu HQ, 2018, BIOCHEM BIOPH RES CO, V503, P2400, DOI 10.1016/j.bbrc.2018.06.168; Huang F, 2018, WORLD J GASTROENTERO, V24, P4643, DOI 10.3748/wjg.v24.i41.4643; Li YC, 2019, ONCOTARGETS THER, V12, P2649, DOI 10.2147/OTT.S188054; Lilo ZP, 2019, EUR MED PHARM SCI, V23, P8788; Niu Q, 2019, YONSEI MED J, V60, P1146, DOI 10.3349/ymj.2019.60.12.1146; Qi Y, 2018, PROC ADAPT LEARN OPT, V9, P1, DOI 10.1007/978-3-319-57421-9_1; Shan Yuying, 2018, ZHEJIANG MED J, V40, P1020; Sun F, 2018, CELL DEATH DIS, V9, P1; Vivacqua A, 2018, CELLS-BASEL, V7, DOI 10.3390/cells7110203; Wang YX, 2018, AM J CANCER RES, V8, P2564; Xian D, 2019, J CELL MOL MED, V23, P3808, DOI 10.1111/jcmm.14071; Xu HW, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0086723; Zhao Jing, 2015, QICJIHAR MED COLL, V36, P477; Zheng L, 2019, EUR REV MED PHARMACO, V23, P6944, DOI 10.26355/eurrev_201908_18734	20	2	2	0	2	C M B  ASSOC	POITIERS	34 BOULEVARD SOLFERINO, 86000 POITIERS, FRANCE	0145-5680	1165-158X		CELL MOL BIOL	Cell. Mol. Biol.		2020	66	3					191	196		10.14715/cmb/2020.66.3.31			6	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	LY3EW	WOS:000540410000031	32538770				2022-04-25	
J	Sakanashi, F; Shintani, M; Tsuneyoshi, M; Ohsaki, H; Kamoshida, S				Sakanashi, Fuminori; Shintani, Michiko; Tsuneyoshi, Masazumi; Ohsaki, Hiroyuki; Kamoshida, Shingo			Apoptosis, necroptosis and autophagy in colorectal cancer: Associations with tumor aggressiveness and p53 status	PATHOLOGY RESEARCH AND PRACTICE			English	Article						Cleaved caspase-3; Colorectal cancer; Microtubule-associated protein-1 light chain-3; Phosphorylated-mixed-lineage kinase domain-like protein; p53; Pathological aggressiveness	CELL-DEATH; MUTATIONS; CARCINOMA; PATHWAYS; SURVIVAL; NECROSIS; BIOLOGY; MARKER; KINASE; LC3	Objective: Cleaved caspase-3 (CC3), phosphorylated-mixed-lineage kinase domain-like protein (p-MLKL), and microtubule-associated protein-1 light chain-3B (LC3B) have pivotal functions in apoptosis, necroptosis, and autophagy, respectively. In vitro studies have shown that interaction of these proteins are complex and their roles in cancer can be influenced by many factors. However, these findings are not adequately assessed in human tissues. Here, we determined CC3, p-MLKL, and LC3B expression in colorectal cancers (CRCs), and assessed their associations with clinicopathological parameters, and with KRAS and p53 status. Methods: We immunohistochemically assessed 113 CRC specimens for levels of CC3, p-MLKL, LC3B, and p53. KRAS gene status was analyzed using the Scorpion-amplification refractory mutation system. Results: High levels of CC3 (CC3(High)) and LC3B (LC3B(High)) were detected in 38% and 35% of the 113 CRCs, respectively, but no or only a few p-MLKL-positive cells were observed in any of the tumors. CC3(High) was significantly associated with high pT status (P = 0.03), vascular invasion (P = 0.03) and high pStage (P = 0.04) and was marginally associated with lymph node (P = 0.06) and distant metastases (P = 0.06). LC3B(High) was also significantly associated with high pT status (P = 0.02) and lymphatic invasion (P = 0.002), and was marginally associated with nerve plexus invasion (P = 0.06). In combined analysis, compared with CC3(Low)/LC3B(Low) tumors, tumors that were either CC3(High), LC3B(High), or both were significantly associated with high pT status (P = 0.0007), lymphatic invasion (P = 0.03), vascular invasion (P = 0.003), distant metastasis (P = 0.04) and high pStage (P = 0.04). LC3B(High) was significantly associated with a mutant-type expression pattern of p53 (P = 0.003). Conclusion: To the best of our knowledge, this is the first study to examine the combination of CC3/LC3B and p-MLKL expression in clinical CRC samples and to correlate these expression data with clinicopathological parameters and EGFR and p53 status. Our results suggest that necroptosis is a rare process in CRC, apoptosis and autophagy are upregulated in aggressive CRCs, and p53 mutation may lead to the upregulation of autophagy.	[Sakanashi, Fuminori; Ohsaki, Hiroyuki; Kamoshida, Shingo] Kobe Univ, Grad Sch Hlth Sci, Dept Med Biophys, Lab Pathol,Suma Ku, 7-10-2 Tomogaoka, Kobe, Hyogo 6540142, Japan; [Sakanashi, Fuminori; Tsuneyoshi, Masazumi] Fukuoka Sanno Hosp, Dept Diagnost Pathol, 3-6-45 Momochihama, Sawara, Fukuoka 8140001, Japan; [Shintani, Michiko] Kobe Tokiwa Univ, Dept Med Technol, 2-6-2 Ohtani, Kobe, Hyogo 6530838, Japan		Sakanashi, F (corresponding author), Kobe Univ, Grad Sch Hlth Sci, Dept Med Biophys, Lab Pathol,Suma Ku, 7-10-2 Tomogaoka, Kobe, Hyogo 6540142, Japan.	sakanashi@kouhoukai.or.jp					Ashkenazi A, 2008, CYTOKINE GROWTH F R, V19, P325, DOI 10.1016/j.cytogfr.2008.04.001; Brierley J., 2016, TNM CLASSIFICATION M, V8th ed; Cheng J, 2015, MOL ONCOL, V9, P105, DOI 10.1016/j.molonc.2014.07.024; Degenhardt K, 2006, CANCER CELL, V10, P51, DOI 10.1016/j.ccr.2006.06.001; Downward J, 2003, NAT REV CANCER, V3, P11, DOI 10.1038/nrc969; FINKELSTEIN SD, 1993, CANCER, V71, P3827, DOI 10.1002/1097-0142(19930615)71:12<3827::AID-CNCR2820711207>3.0.CO;2-N; Fulda S, 2013, CANCER BIOL THER, V14, P999, DOI 10.4161/cbt.26428; Gown AM, 2002, J HISTOCHEM CYTOCHEM, V50, P449, DOI 10.1177/002215540205000401; Haupt S, 2003, J CELL SCI, V116, P4077, DOI 10.1242/jcs.00739; Hayashi H, 1998, APOPTOSIS, V3, P431, DOI 10.1023/A:1009662619907; Hector S, 2009, BBA-REV CANCER, V1795, P117, DOI 10.1016/j.bbcan.2008.12.002; Huang Q, 2011, NAT MED, V17, P860, DOI 10.1038/nm.2385; JACOBSON MD, 1995, NATURE, V374, P814, DOI 10.1038/374814a0; Jiang YX, 2009, CANCER-AM CANCER SOC, V115, P3609, DOI 10.1002/cncr.24434; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; KERR JFR, 1972, BRIT J CANCER, V26, P239, DOI 10.1038/bjc.1972.33; Klionsky DJ, 2000, SCIENCE, V290, P1717, DOI 10.1126/science.290.5497.1717; Kumar R, 2005, Int J Surg, V3, P268, DOI 10.1016/j.ijsu.2005.05.002; Kumar S, 2007, CELL DEATH DIFFER, V14, P32, DOI 10.1038/sj.cdd.4402060; Levy JMM, 2017, NAT REV CANCER, V17, P528, DOI 10.1038/nrc.2017.53; Li XL, 2015, WORLD J GASTROENTERO, V21, P84, DOI 10.3748/wjg.v21.i1.84; Long JS, 2012, ONCOGENE, V31, P5045, DOI 10.1038/onc.2012.7; Mathew R, 2007, NAT REV CANCER, V7, P961, DOI 10.1038/nrc2254; Moujalled DM, 2014, CELL DEATH DIS, V5, DOI 10.1038/cddis.2014.18; Nunez G, 1998, ONCOGENE, V17, P3237, DOI 10.1038/sj.onc.1202581; Patel S, 2016, ONCOTARGET, V7, P59087, DOI 10.18632/oncotarget.10824; Pouyssegur J, 2006, NATURE, V441, P437, DOI 10.1038/nature04871; Sabine VS, 2012, HISTOPATHOLOGY, V60, P369, DOI 10.1111/j.1365-2559.2011.04024.x; Scherz-Shouval R, 2010, P NATL ACAD SCI USA, V107, P18511, DOI 10.1073/pnas.1006124107; Schmitz KJ, 2016, WORLD J SURG ONCOL, V14, DOI 10.1186/s12957-016-0946-x; Sharifi MN, 2016, CELL REP, V15, P1660, DOI 10.1016/j.celrep.2016.04.065; Shintani M, 2011, BIOMED RES-TOKYO, V32, P379, DOI 10.2220/biomedres.32.379; Su ZY, 2015, MOL CANCER, V14, DOI 10.1186/s12943-015-0321-5; Sun LM, 2012, CELL, V148, P213, DOI 10.1016/j.cell.2011.11.031; Tasdemir E, 2008, NAT CELL BIOL, V10, P676, DOI 10.1038/ncb1730; Vandenabeele P, 2010, NAT REV MOL CELL BIO, V11, P700, DOI 10.1038/nrm2970; Yemelyanova A, 2011, MODERN PATHOL, V24, P1248, DOI 10.1038/modpathol.2011.85; Yu J, 2005, BIOCHEM BIOPH RES CO, V331, P851, DOI 10.1016/j.bbrc.2005.03.189; Zhang L, 2013, CURR COLORECT CANC R, V9, P331, DOI 10.1007/s11888-013-0188-z; Zhang ZX, 2015, J EXP CLIN CANC RES, V34, DOI 10.1186/s13046-015-0166-1; Zheng Hai-yang, 2012, Cancer Biology Medicine, V9, P105, DOI 10.3969/j.issn.2095-3941.2012.02.004	41	9	10	0	10	ELSEVIER GMBH	MUNICH	HACKERBRUCKE 6, 80335 MUNICH, GERMANY	0344-0338			PATHOL RES PRACT	Pathol. Res. Pract.	JUL	2019	215	7							152425	10.1016/j.prp.2019.04.017			6	Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Pathology	IH7HH	WOS:000474674200022	31097354	Green Published			2022-04-25	
J	Voloshin, T; Kaynan, N; Davidi, S; Porat, Y; Shteingauz, A; Schneiderman, RS; Zeevi, E; Munster, M; Blat, R; Brami, CT; Cahal, S; Itzhaki, A; Giladi, M; Kirson, ED; Weinberg, U; Kinzel, A; Palti, Y				Voloshin, Tali; Kaynan, Noa; Davidi, Shiri; Porat, Yaara; Shteingauz, Anna; Schneiderman, Rosa S.; Zeevi, Einav; Munster, Mijal; Blat, Roni; Tempel Brami, Catherine; Cahal, Shay; Itzhaki, Aviran; Giladi, Moshe; Kirson, Eilon D.; Weinberg, Uri; Kinzel, Adrian; Palti, Yoram			Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy	CANCER IMMUNOLOGY IMMUNOTHERAPY			English	Article						Tumor-treating fields; Anti-PD-1; ER stress; Immunogenic cell death; Autophagy	CALRETICULIN EXPOSURE; ATP SECRETION; AUTOPHAGY; BLOCKADE; CHEMOTHERAPY; PROGRESSION; MECHANISMS; RESPONSES; RELEASE; MODELS	Tumor-treating fields (TTFields) are alternating electric fields in a specific frequency range (100-300 kHz) delivered to the human body through transducer arrays. In this study, we evaluated whether TTFields-mediated cell death can elicit antitumoral immunity and hence would be effectively combined with anti-PD-1 therapy. We demonstrate that in TTFields-treated cancer cells, damage-associated molecular patterns including high-mobility group B1 and adenosine triphosphate are released and calreticulin is exposed on the cell surface. Moreover, we show that TTFields treatment promotes the engulfment of cancer cells by dendritic cells (DCs) and DCs maturation in vitro, as well as recruitment of immune cells in vivo. Additionally, our study demonstrates that the combination of TTFields with anti-PD-1 therapy results in a significant decline of tumor volume and increase in the percentage of tumor-infiltrating leukocytes in two tumor models. In orthotopic lung tumors, these infiltrating leukocytes, specifically macrophages and DCs, showed elevated expression of PD-L1. Compatibly, cytotoxic T-cells isolated from these tumors demonstrated increased production of IFN-gamma. In colon cancer tumors, T-cells infiltration was significantly increased following long treatment duration with TTFields plus anti-PD-1. Collectively, our results suggest that TTFields therapy can induce anticancer immune response. Furthermore, we demonstrate robust efficacy of concomitant application of TTFields and anti-PD-1 therapy. These data suggest that integrating TTFields with anti-PD-1 therapy may further enhance antitumor immunity, hence achieve better tumor control.	[Voloshin, Tali; Kaynan, Noa; Davidi, Shiri; Porat, Yaara; Shteingauz, Anna; Schneiderman, Rosa S.; Zeevi, Einav; Munster, Mijal; Blat, Roni; Tempel Brami, Catherine; Cahal, Shay; Itzhaki, Aviran; Giladi, Moshe; Kirson, Eilon D.; Weinberg, Uri; Palti, Yoram] Novocure Ltd, MATAM Ctr, Topaz Bldg, IL-31905 Haifa, Israel; [Kinzel, Adrian] Novocure GmbH, Munich, Germany		Giladi, M (corresponding author), Novocure Ltd, MATAM Ctr, Topaz Bldg, IL-31905 Haifa, Israel.	mosheg@novocure.com					Arlauckas SP, 2017, SCI TRANSL MED, V9, DOI 10.1126/scitranslmed.aal3604; Bezu L, 2018, ONCOIMMUNOLOGY, V7, DOI 10.1080/2162402X.2018.1431089; Capasso A, 2019, J IMMUNOTHER CANCER, V7, DOI 10.1186/s40425-019-0518-z; Dupont N, 2014, METHOD ENZYMOL, V543, P73, DOI 10.1016/B978-0-12-801329-8.00004-0; Elliott MR, 2009, NATURE, V461, P282, DOI 10.1038/nature08296; Garg AD, 2012, EMBO J, V31, P1062, DOI 10.1038/emboj.2011.497; Georgoudaki AM, 2016, CELL REP, V15, P2000, DOI 10.1016/j.celrep.2016.04.084; Gera N, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0125269; Giladi M, 2015, SCI REP-UK, V5, DOI 10.1038/srep18046; Goldszmid RS, 2012, IMMUNITY, V36, P1047, DOI 10.1016/j.immuni.2012.03.026; Green DR, 2009, NAT REV IMMUNOL, V9, P353, DOI 10.1038/nri2545; Hu ZSI, 2017, CURR BREAST CANCER R, V9, P45, DOI 10.1007/s12609-017-0234-y; Kazama H, 2008, IMMUNITY, V29, P21, DOI 10.1016/j.immuni.2008.05.013; Kirson ED, 2004, CANCER RES, V64, P3288, DOI 10.1158/0008-5472.CAN-04-0083; Kirson ED, 2007, P NATL ACAD SCI USA, V104, P10152, DOI 10.1073/pnas.0702916104; Kirson ED, 2009, CLIN EXP METASTAS, V26, P633, DOI 10.1007/s10585-009-9262-y; Kleinovink JW, 2017, CANCER IMMUNOL RES, V5, P832, DOI 10.1158/2326-6066.CIR-17-0055; Lechner MG, 2013, J IMMUNOTHER, V36, P477, DOI 10.1097/01.cji.0000436722.46675.4a; Martins I, 2014, CELL DEATH DIFFER, V21, P79, DOI 10.1038/cdd.2013.75; Martins I, 2009, CELL CYCLE, V8, P3723, DOI 10.4161/cc.8.22.10026; McNamara MJ, 2016, CANCER IMMUNOL RES, V4, P650, DOI 10.1158/2326-6066.CIR-16-0022; Messmer D, 2004, J IMMUNOL, V173, P307, DOI 10.4049/jimmunol.173.1.307; Michaud M, 2011, SCIENCE, V334, P1573, DOI 10.1126/science.1208347; Obeid M, 2007, CELL DEATH DIFFER, V14, P1848, DOI 10.1038/sj.cdd.4402201; Obeid M, 2007, NAT MED, V13, P54, DOI 10.1038/nm1523; Panaretakis T, 2009, EMBO J, V28, P578, DOI 10.1038/emboj.2009.1; Pardoll DM, 2012, NAT REV CANCER, V12, P252, DOI 10.1038/nrc3239; Porat Y, 2017, JOVE-J VIS EXP, DOI 10.3791/55820; Ribas A, 2017, CELL, V170, P1109, DOI 10.1016/j.cell.2017.08.027; Ribas A, 2015, CANCER DISCOV, V5, P915, DOI 10.1158/2159-8290.CD-15-0563; Roberts PC, 2005, NEOPLASIA, V7, P944, DOI 10.1593/neo.05358; Scaffidi P, 2002, NATURE, V418, P191, DOI 10.1038/nature00858; Senovilla L, 2012, SCIENCE, V337, P1678, DOI 10.1126/science.1224922; Silginer M, 2017, CELL DEATH DIS, V8, DOI 10.1038/cddis.2017.171; Stingele S, 2013, AUTOPHAGY, V9, P246, DOI 10.4161/auto.22558; Sun L, 2019, JCI INSIGHT, V4, DOI 10.1172/jci.insight.126853; Topalian SL, 2015, CANCER CELL, V27, P450, DOI 10.1016/j.ccell.2015.03.001; Tumeh PC, 2014, NATURE, V515, P568, DOI 10.1038/nature13954; Vonderheide RH, 2018, CANCER CELL, V33, P563, DOI 10.1016/j.ccell.2018.03.008; Wong ET, 2015, BRIT J CANCER, V113, P232, DOI 10.1038/bjc.2015.238; Wong ET, 2014, CANCER MED-US, V3, P592, DOI 10.1002/cam4.210; Yatim N, 2017, NAT REV IMMUNOL, V17, P262, DOI 10.1038/nri.2017.9; Yu JW, 2018, PLOS ONE, V13, DOI 10.1371/journal.pone.0206223	43	22	27	3	20	SPRINGER	NEW YORK	ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES	0340-7004	1432-0851		CANCER IMMUNOL IMMUN	Cancer Immunol. Immunother.	JUL	2020	69	7					1191	1204		10.1007/s00262-020-02534-7			14	Oncology; Immunology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Immunology	LZ2QV	WOS:000541074000005	32144446	Green Published, hybrid			2022-04-25	
J	Lu, CL; Qin, LL; Liu, HC; Candas, D; Fan, M; Li, JJ				Lu, Chung-Ling; Qin, Lili; Liu, Hsin-Chen; Candas, Demet; Fan, Ming; Li, Jian Jian			Tumor Cells Switch to Mitochondrial Oxidative Phosphorylation under Radiation via mTOR-Mediated Hexokinase II Inhibition - A Warburg-Reversing Effect	PLOS ONE			English	Article							MAMMALIAN TARGET; CANCER-CELLS; UP-REGULATION; RAPAMYCIN; PATHWAY; GROWTH; METABOLISM; NVP-BEZ235; AUTOPHAGY; STRESS	A unique feature of cancer cells is to convert glucose into lactate to produce cellular energy, even under the presence of oxygen. Called aerobic glycolysis [The Warburg Effect] it has been extensively studied and the concept of aerobic glycolysis in tumor cells is generally accepted. However, it is not clear if aerobic glycolysis in tumor cells is fixed, or can be reversed, especially under therapeutic stress conditions. Here, we report that mTOR, a critical regulator in cell proliferation, can be relocated to mitochondria, and as a result, enhances oxidative phosphorylation and reduces glycolysis. Three tumor cell lines (breast cancer MCF-7, colon cancer HCT116 and glioblastoma U87) showed a quick relocation of mTOR to mitochondria after irradiation with a single dose 5 Gy, which was companied with decreased lactate production, increased mitochondrial ATP generation and oxygen consumption. Inhibition of mTOR by rapamycin blocked radiation-induced mTOR mitochondrial relocation and the shift of glycolysis to mitochondrial respiration, and reduced the clonogenic survival. In irradiated cells, mTOR formed a complex with Hexokinase II [HK II], a key mitochondrial protein in regulation of glycolysis, causing reduced HK II enzymatic activity. These results support a novel mechanism by which tumor cells can quickly adapt to genotoxic conditions via mTOR-mediated reprogramming of bioenergetics from predominantly aerobic glycolysis to mitochondrial oxidative phosphorylation. Such a "waking-up" pathway for mitochondrial bioenergetics demonstrates a flexible feature in the energy metabolism of cancer cells, and may be required for additional cellular energy consumption for damage repair and survival. Thus, the reversible cellular energy metabolisms should be considered in blocking tumor metabolism and may be targeted to sensitize them in anti-cancer therapy.	[Lu, Chung-Ling; Qin, Lili; Liu, Hsin-Chen; Candas, Demet; Fan, Ming; Li, Jian Jian] Univ Calif Davis, Sch Med, Dept Radiat Oncol, Sacramento, CA 95817 USA		Li, JJ (corresponding author), Univ Calif Davis, Sch Med, Dept Radiat Oncol, Sacramento, CA 95817 USA.	jijli@ucdavis.edu	Qin, Lili/J-7481-2016	Li, Jian Jian/0000-0003-3694-9675	National Institutes of Health RO1United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [CA133402, CA152313]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA133402, R01CA152313, P30CA093373] Funding Source: NIH RePORTER	This study was supported by National Institutes of Health RO1 Grants CA133402 and CA152313 to JL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Bialy, LP; Kuckelkorn, U; Henklein, P; Fayet, J; Wilczynski, GM; Kaminski, A; Mlynarczuk-Bialy, I				Bialy, L. P.; Kuckelkorn, U.; Henklein, P.; Fayet, J.; Wilczynski, G. M.; Kaminski, A.; Mlynarczuk-Bialy, I			Changes in spatio-temporal localization of tripeptidyl peptidase II (TPPII) in murine colon adenocarcinoma cells during aggresome formation: a microscopy study based on a novel fluorescent proteasome inhibitor	HISTOLOGY AND HISTOPATHOLOGY			English	Article						TPPII; Proteasome; Ubiquitin; Aggresome; Proteasome inhibitor BSc2118	CHYMOTRYPSIN-LIKE ACTIVITY; BSC2118; DEGRADATION; BORTEZOMIB; AUTOPHAGY; UBIQUITIN; PROTEOLYSIS; APOPTOSIS; CASPASES; PROTEINS	Extralysosomal proteolysis is a multistep process involving the Ubiquitin- Proteasome System (UPS) and supplementary peptidases. Tripeptidyl peptidase II (TPPII) is the most extensively characterized enzyme, supplementing and sometimes substituting for proteasomal functions. In response to proteasome inhibition, polyubiquitinated proteins acting as proteasome substrates aggregate with proteasomes and form aggresomes. Several proteasome inhibitors are used as anti-cancer drugs. Thus, in our study, we used a novel fluorescent-tagged proteasome inhibitor BSc2118 to induce aggresome formation in C26 murine colon adenocarcinoma cells. It allowed us to obtain effective, inhibitor-based, proteasome staining in vivo. This method has been validated by standard post-fixed indirect immunostaining and also allowed co-immunodetection of TPPII and polyubiquitinated proteins under laser scanning confocal microscopy. We found that in the absence of the inhibitor, TPPH is diffusely dispersed within the cytoplasm of C26 cells. The proteasome and ubiquitin-rich perinuclear region failed to display enhanced TPPII staining. However, when proteasome function was impaired by the inhibitor, TPPII associated more closely with both the proteasome and polyubiquitinated proteins via TPPII recruitment to the perinuclear region and subsequently into emerging aggresomal structures. Furthermore, we have demonstrated the dynamic recruitment of TPPII into the developing aggresome: TPPII in the early aggresome was dispersed within the central part but subsequently aggregated on the surface of this structure. In the mature aggresome of C26 cells TPPII formed a spherical mantle, which surrounded the round core containing proteasomes and polyubiquitinated proteins. Our morphological data indicate that TPPII displays spatial localization with proteasomes especially upon proteasome inhibition in aggresomes of C26 cells.	[Bialy, L. P.; Mlynarczuk-Bialy, I] Med Univ Warsaw, Ctr Biostruct Res, Dept Histol & Embryol, Chalubinskiego 5, PL-02004 Warsaw, Poland; [Kuckelkorn, U.; Henklein, P.] Charite Univ Med Berlin, Inst Biochem, Berlin, Germany; [Fayet, J.] Med Univ Warsaw, Med Fac 1, Dept Ophthalmol, Warsaw, Poland; [Wilczynski, G. M.] Nencki Inst Expt Biol PAS, Dept Neurophysiol, Lab Mol & Syst Neuromorphol, Warsaw, Poland; [Kaminski, A.] Med Univ Warsaw, Ctr Biostruct Res, Dept Transplantol, Warsaw, Poland; [Kaminski, A.] Med Univ Warsaw, Ctr Biostruct Res, Cent Tissue Bank, Warsaw, Poland		Mlynarczuk-Bialy, I (corresponding author), Med Univ Warsaw, Ctr Biostruct Res, Dept Histol & Embryol, Chalubinskiego 5, PL-02004 Warsaw, Poland.	izamlynar@esculap.pl	Mlynarczuk-Bialy, Izabela/AAA-2064-2022; Biały, Lukasz/AAW-8500-2021	Mlynarczuk-Bialy, Izabela/0000-0002-5192-6415; Wilczynski, Grzegorz/0000-0001-6667-0291; Henklein, Petra/0000-0001-7468-8926; Bialy, Lukasz/0000-0001-6931-6431; Kuckelkorn, Ulrike/0000-0002-3085-9161	European Regional Development FundEuropean Commission [1M15/WB2/10]; Polish National Center [POIG 01.01.02-00-008/08];  [UMO-2013/08/M/NZ3/00655]	The work was supported by financial resources of Medical University of Warsaw (1M15/WB2/10) to LB and by the European Regional Development Fund POIG 01.01.02-00-008/08, and by the grant from Polish National Center no. 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Histopath.	APR	2019	34	4					359	372		10.14670/HH-18-042			14	Cell Biology; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Pathology	HM5UA	WOS:000459539500005	30226264				2022-04-25	
J	Jiang, Q; Li, F; Shi, K; Wu, P; An, J; Yang, Y; Xu, C				Jiang, Q.; Li, F.; Shi, K.; Wu, P.; An, J.; Yang, Y.; Xu, C.			Involvement of p38 in signal switching from autophagy to apoptosis via the PERK/eIF2 alpha/ATF4 axis in selenite-treated NB4 cells	CELL DEATH & DISEASE			English	Article						p38; selenite; autophagy; apoptosis; p53	ACUTE PROMYELOCYTIC LEUKEMIA; COLON-CANCER CELLS; ER STRESS; ENDOPLASMIC-RETICULUM; P53; EXPRESSION; GENE; ATF4; PHOSPHORYLATION; TRANSCRIPTION	Selenite has emerged as an optional chemotherapeutic agent for hematological malignancies. Autophagy and apoptosis are both engaged in selenite-induced cell death. In a previous report, we have identified heat shock protein 90 (Hsp90) as a critical modulator of the balance between autophagy and apoptosis in selenite-treated leukemia cells. However, the mechanisms by which selenite mediates the crosstalk between autophagy and apoptosis remain largely unknown. Herein, we demonstrate that the endoplasmic reticulum (ER) stress-related PERK/eIF2 alpha/ATF4 pathway and p38 are core modules for the selenite-induced switch to apoptosis from autophagy. We found that selenite activated PERK and eIF2 alpha/ATF4 downstream to promote apoptosis. During this progression, p38 was dissociated from PERK-inhibiting Hsp90 and became autophosphorylated. Then, activated p38 further enhanced the docking of activating transcription factor 4 (ATF4) onto the CHOP (CCAAT/enhancer-binding protein homologous protein) promoter via eIF2 alpha to enhance apoptosis. We also found that activated p38 suppressed the phosphorylation of eIF4E that directed ATF4 to bind to the MAP1LC3B (microtubule-associated protein 1 light chain 3B) promoter. Because of the deactivation of eIF4E, the association of ATF4 with the MAP1LC3B promoter was inhibited, and autophagy was compromised. Intriguingly, p53 played important roles in mediating the p38-mediated regulation of eIF2 alpha and eIF4E. When activated by p38, p53 induced the phosphorylation of eIF2 alpha and the dephosphorylation of eIF4E, particularly in the nucleus where the ATF4 transcription factor was modulated, ultimately resulting in differential expression of CHOP and LC3. Moreover, selenite exhibited potent antitumor effects in vivo. In an NB4 cell xenograft model, selenite induced apoptosis and hampered autophagy. In addition, related signaling proteins demonstrated similar changes to those observed in vitro. These data suggest that selenite may be a candidate drug for leukemia therapy.	[Jiang, Q.; Li, F.; Shi, K.; Wu, P.; An, J.; Yang, Y.; Xu, C.] PUMC, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100005, Peoples R China; [Jiang, Q.; Li, F.; Shi, K.; Wu, P.; An, J.; Yang, Y.; Xu, C.] PUMC, Sch Basic Med, Beijing 100005, Peoples R China; [Jiang, Q.; Li, F.; Shi, K.; Wu, P.; An, J.; Yang, Y.; Xu, C.] CAMS, Beijing 100005, Peoples R China		Xu, C (corresponding author), CAMS, Inst Basic Med Sci, Dept Biochem & Mol Biol, 5 DongdanSantiao, Beijing 100005, Peoples R China.	cmxu@ibms.pumc.edu.cn		Wu, Pa/0000-0002-7269-0683	National Natural Sciences Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31170788, 30970655]; National Natural Science Foundation for Young Scholars of ChinaNational Natural Science Foundation of China (NSFC)National Science Fund for Distinguished Young Scholars [31101018]; Natural Science Foundation of BeijingBeijing Natural Science Foundation [5082015]; State Key Laboratory Special Fund [2060204]; Ministry of Education, China, for Doctor-training UniteMinistry of Education, China [20091106110025]	We thank Dr. L Pan (China-Japan Friendship Hospital) for her expertise in immunocytochemistry assay. This work was supported by grants from the National Natural Sciences Foundation of China (No. 31170788 and No. 30970655), the National Natural Science Foundation for Young Scholars of China (No. 31101018), the Natural Science Foundation of Beijing (No. 5082015), the State Key Laboratory Special Fund (No. 2060204) and the Ministry of Education, China, for Doctor-training Unite (No. 20091106110025).	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MAY	2014	5				SI				e1270	10.1038/cddis.2014.200			13	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	AI9DN	WOS:000337229300070	24874742	Green Published, gold			2022-04-25	
J	Yang, KM; Kim, BM; Park, JB				Yang, Kyung Mi; Kim, Byeong Mo; Park, Jin-Byung			omega-Hydroxyundec-9-enoic acid induces apoptosis through ROS-mediated endoplasmic reticulum stress in non-small cell lung cancer cells	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						omega-Hydroxyundec-9-enoic acid (omega-HUA); Non-small cell lung cancer (NSCLC); Apoptosis; Endoplasmic reticulum (ER) stress; Reactive oxygen species (ROS); N-Acetyl-L-cysteine (NAC)	FATTY-ACIDS; ER STRESS; COLON-CANCER; OXIDATIVE STRESS; LIVER-CELLS; INHIBITION; ACTIVATION; INDUCTION; AUTOPHAGY; ARREST	omega-Hydroxyundec-9-enoic acid (omega-HUA), a hydroxyl unsaturated fatty acid derivative, is involved in the antifungal activity of wild rice (Oryza officinalis). Here, we investigated the anti-cancer activity of omega-HUA on a non-small cell lung cancer (NSCLC) cell line. omega-HUA increased apoptosis and induced cleavages of caspase-6, caspase-9, and poly (ADP-ribose) polymerase (PARP). omega-HUA treatment significantly induced endoplasmic reticulum (ER) stress response. Suppression of CHOP expression and inhibiting ER stress by 4-phenylbutyrate (4-PBA) significantly attenuated the omega-HUA treatment-induced activation of caspase-6, caspase-9, and PARP, and subsequent apoptotic cell death, indicating a role for ER stress in omega-HUA-induced apoptosis. In addition, cells subjected to omega-HUA exhibited significantly increased quantity of reactive oxygen species (ROS), and the ROS scavenger N-acetyl-L-cysteine (NAC) inhibited omega-HUA-induced apoptotic cell death and ER stress signals, indicating a role for ROS in ER stress-mediated apoptosis in omega-HUA-treated cells. Taken together, these results suggest that sequential ROS generation and ER stress activation are critical in omega-HUA treatment-induced apoptosis and that omega-HUA represents a promising candidate for NSCLC treatment. (C) 2014 Elsevier Inc. All rights reserved.	[Yang, Kyung Mi] Yonsei Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 120749, South Korea; [Kim, Byeong Mo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Gerontol, Boston, MA 02215 USA; [Park, Jin-Byung] Ewha Womans Univ, Dept Food Sci & Engn, Seoul 120750, South Korea		Park, JB (corresponding author), Ewha Womans Univ, Dept Food Sci & Engn, 52 Ewhayeodae Gil, Seoul 120750, South Korea.	jbpark06@ewha.ac.kr			Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF-2012R1A1A2042157]	The present study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2012R1A1A2042157).	Cao J, 2012, MOL CELL BIOCHEM, V364, P115, DOI 10.1007/s11010-011-1211-9; Cury-Boaventura MF, 2005, CLIN SCI, V108, P245, DOI 10.1042/CS20040281; Eitel K, 2002, BIOCHEM BIOPH RES CO, V299, P853, DOI 10.1016/S0006-291X(02)02752-3; Fukui M, 2013, J CELL BIOCHEM, V114, P192, DOI 10.1002/jcb.24354; Gasmi J, 2013, PHYTOMEDICINE, V20, P734, DOI 10.1016/j.phymed.2013.01.012; Hanada S, 2007, J HEPATOL, V47, P93, DOI 10.1016/j.jhep.2007.01.039; Jakobsen CH, 2008, J LIPID RES, V49, P2089, DOI 10.1194/jlr.M700389-JLR200; Malhotra JD, 2007, ANTIOXID REDOX SIGN, V9, P2277, DOI 10.1089/ars.2007.1782; Park EJ, 2014, FOOD CHEM TOXICOL, V67, P26, DOI 10.1016/j.fct.2014.01.027; Parolin C, 2012, BBA-MOL CELL BIOL L, V1821, P1334, DOI 10.1016/j.bbalip.2012.07.007; Pierre AS, 2013, BBA-MOL CELL BIOL L, V1831, P759, DOI 10.1016/j.bbalip.2013.01.005; Rovito D, 2013, J CELL PHYSIOL, V228, P1314, DOI 10.1002/jcp.24288; Sano R, 2013, BBA-MOL CELL RES, V1833, P3460, DOI 10.1016/j.bbamcr.2013.06.028; Song JW, 2013, ANGEW CHEM INT EDIT, V52, P2534, DOI 10.1002/anie.201209187; SUZUKI Y, 1995, BIOSCI BIOTECH BIOCH, V59, P2049, DOI 10.1271/bbb.59.2049; Wei YR, 2006, AM J PHYSIOL-ENDOC M, V291, pE275, DOI 10.1152/ajpendo.00644.2005; Xu HY, 2013, EUR J PHARMACOL, V700, P13, DOI 10.1016/j.ejphar.2012.11.015; Zhang Y, 2012, LIPIDS HEALTH DIS, V11, DOI 10.1186/1476-511X-11-1	18	21	22	1	17	ACADEMIC PRESS INC ELSEVIER SCIENCE	SAN DIEGO	525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA	0006-291X	1090-2104		BIOCHEM BIOPH RES CO	Biochem. Biophys. Res. Commun.	JUN 6	2014	448	3					267	273		10.1016/j.bbrc.2014.04.111			7	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	AI7KZ	WOS:000337070800005	24796672				2022-04-25	
J	Eom, JM; Seo, MJ; Baek, JY; Chu, H; Han, SH; Min, TS; Cho, CS; Yun, CH				Eom, Jung-Min; Seo, Min-Ji; Baek, Ji-Young; Chu, Hyuk; Han, Seung Hyun; Min, Tae Sun; Cho, Chong-Su; Yun, Cheol-Heui			Alpha-eleostearic acid induces autophagy-dependent cell death through targeting AKT/mTOR and ERK1/2 signal together with the generation of reactive oxygen species	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						Alpha-eleostearic acid; Reactive oxygen species; Apoptosis; Autophagy	CONJUGATED TRIENE SYSTEM; COLON-CANCER CELLS; OXIDATIVE STRESS; MAMMALIAN TARGET; FATTY-ACIDS; IN-VIVO; APOPTOSIS; TUMOR; PATHWAYS; AKT	Alpha-eleostearic acid (alpha-ESA, 9Z11E13E-18.3). a linolenic acid isomer with a conjugated triene system. is a natural and biologically-active Compound that has been shown to possess potent anti-tumor properties Herein, we demonstrate alpha-ESA induced apoptosis and autophagy with reactive oxygen species (ROS) generation in HeLa cells Treatment with alpha-ESA caused inhibition of phosphorylated (p)AKT and elongated the sub G1 phase in the cell cycle. indicating induction of apoptosis. Autophagy was also induced by alpha-ESA treatment, causing low pAKT and pP70S6K activities, increasing pERK1/2 and leading to a higher conversion rate of LC3 I to LC3 II compared to that of the control. The autophagy was further confirmed by fluorescence microscopy and flow cytometry through monodansylcadavarine (MDC) staining It appears that the role of autophagy is a protective mechanism against cell death in alpha-ESA-treated HeLa cells. Subsequently, we found that treating HeLa cells with alpha-ESA induced the generation of reactive oxygen species (ROS) The phosphorylation of P70S6K. downstream of mTOR signaling, and AKT were further reduced by pretreatment with N-acetyl-L-cysteine (NAC), an ROS scavenger, whereas the phosphorylation of ERK1/2 and the conversion of LC3 I to LC3 II were further enhanced As a result, the blocking of the action of ROS promoted alpha-ESA-induced apoptosis and autophagy. Taken together, our results indicate that the generation of ROS by alpha-ESA treatment impedes the progress of apoptosis and excessive autophagy formation which takes part in cell death, thus impeding death promotion. (C) 2009 Elsevier Inc All rights reserved	[Yun, Cheol-Heui] Seoul Natl Univ, Dept Agr Biotechnol & Res, Inst Agr & Life Sci, Lab Prot Engn & Comparat Immunol, Seoul 151921, South Korea; [Min, Tae Sun] Natl Res Fdn Korea, Taejon 305350, South Korea; [Han, Seung Hyun] Seoul Natl Univ, Sch Dent, Dept Oral Microbiol & Immunol, Seoul 151921, South Korea; [Han, Seung Hyun] Seoul Natl Univ, Sch Dent, Dent Res Inst, Seoul 151921, South Korea; [Chu, Hyuk] Korea Ctr Dis Control & Prevent, Natl Inst Hlth, Div Zoonoses, Ctr Immunol & Pathol, Seoul, South Korea		Yun, CH (corresponding author), Seoul Natl Univ, Dept Agr Biotechnol & Res, Inst Agr & Life Sci, Lab Prot Engn & Comparat Immunol, 599 Gwanakro, Seoul 151921, South Korea.		YUN, Cheol-Heui/AAR-2775-2020	YUN, Cheol-Heui/0000-0002-0041-2887	Rural Development AdministrationRural Development Administration (RDA) [20080401 034054]; Ministry of Education, Science and TechnologyMinistry of Education, Science and Technology, Republic of Korea [2008-01571]	This work was Supported by the Biogreen 21 program (20080401 034054), Rural Development Administration and by the Expansion of Nuclear R&D Infrastructure Program through the Korea Science and Engineering Foundation funded by the Ministry of Education, Science and Technology (2008-01571). We thank the National Instrumentation Center for Environmental Management (NICEM), Seoul National University for providing the transmission electron microscope.	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Biophys. Res. Commun.	JAN 1	2010	391	1					903	908		10.1016/j.bbrc.2009.11.161			6	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	544AV	WOS:000273624500159	19951696				2022-04-25	
J	Dorsam, B; Seiwert, N; Foersch, S; Stroh, S; Nagel, G; Begaliew, D; Diehl, E; Kraus, A; McKeague, M; Minneker, V; Roukos, V; Reissig, S; Waisman, A; Moehler, M; Stier, A; Mangerich, A; Dantzer, F; Kaina, B; Fahrer, J				Doersam, Bastian; Seiwert, Nina; Foersch, Sebastian; Stroh, Svenja; Nagel, Georg; Begaliew, Diana; Diehl, Erika; Kraus, Alexander; McKeague, Maureen; Minneker, Vera; Roukos, Vassilis; Reissig, Sonja; Waisman, Ari; Moehler, Markus; Stier, Anna; Mangerich, Aswin; Dantzer, Francoise; Kaina, Bernd; Fahrer, Joerg			PARP-1 protects against colorectal tumor induction, but promotes inflammation-driven colorectal tumor progression	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA			English	Article						DNA repair; PARP-1; colorectal carcinogenesis; mouse models; intestinal inflammation	ADP-RIBOSE POLYMERASE-1; DNA-DAMAGE; POLY(ADP-RIBOSE) POLYMERASE; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; MUCOSAL INJURY; DEFICIENT MICE; CANCER CELLS; IN-VIVO; REPAIR; INHIBITION	Colorectal cancer (CRC) is one of the most common tumor entities, which is causally linked to DNA repair defects and inflammatory bowel disease (IBD). Here, we studied the role of the DNA repair protein poly(ADP-ribose) polymerase-1 (PARP-1) in CRC. Tissue microarray analysis revealed PARP-1 overexpression in human CRC, correlating with disease progression. To elucidate its function in CRC, PARP-1 deficient (PARP-1(-/-)) and wild-type animals (WT) were subjected to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colorectal carcinogenesis. Miniendoscopy showed significantly more tumors in WT than in PARP-1(-/-) mice. Although the lack of PARP-1 moderately increased DNA damage, both genotypes exhibited comparable levels of AOM-induced autophagy and cell death. Interestingly, miniendoscopy revealed a higher AOM/DSS-triggered intestinal inflammation in WT animals, which was associated with increased levels of innate immune cells and proinflammatory cytokines. Tumors in WT animals were more aggressive, showing higher levels of STAT3 activation and cyclin D1 up-regulation. PARP-1(-/-) animals were then crossed with O(6-)methylguanine-DNA methyltransferase (MGMT)-deficient animals hypersensitive to AOM. Intriguingly, PARP-1(-/-)/MGMT(-/-)double knockout (DKO) mice developed more, but much smaller tumors than MGMT(-/-) animals. In contrast to MGMT-deficient mice, DKO animals showed strongly reduced AOM-dependent colonic cell death despite similar O-6-methylguanine levels. Studies with PARP-1(-/-) cells provided evidence for increased alkylation-induced DNA strand break formation when MGMT was inhibited, suggesting a role of PARP-1 in the response to O-6-methylguanine adducts. Our findings reveal PARP-1 as a double-edged sword in colorectal carcinogenesis, which suppresses tumor initiation following DNA alkylation in a MGMT-dependent manner, but promotes inflammation-driven tumor progression.	[Doersam, Bastian; Seiwert, Nina; Stroh, Svenja; Nagel, Georg; Begaliew, Diana; Diehl, Erika; Kraus, Alexander; Kaina, Bernd; Fahrer, Joerg] Univ Med Ctr Mainz, Dept Toxicol, D-55131 Mainz, Germany; [Seiwert, Nina; Fahrer, Joerg] Justus Liebig Univ Giessen, Rudolf Buchheim Inst Pharmacol, D-35392 Giessen, Germany; [Foersch, Sebastian] Univ Med Ctr Mainz, Inst Pathol, D-55131 Mainz, Germany; [McKeague, Maureen] ETH, Dept Hlth Sci & Technol, CH-8092 Zurich, Switzerland; [Minneker, Vera; Roukos, Vassilis] Inst Mol Biol, D-55128 Mainz, Germany; [Reissig, Sonja; Waisman, Ari] Univ Med Ctr Mainz, Inst Mol Med, D-55131 Mainz, Germany; [Moehler, Markus] Univ Med Ctr Mainz, Dept Internal Med 1, D-55131 Mainz, Germany; [Stier, Anna; Mangerich, Aswin] Univ Konstanz, Dept Biol, Mol Toxicol Grp, D-78457 Constance, Germany; [Dantzer, Francoise] Ecole Biotechnol Strasbourg, Inst Rech, F-67412 Illkirch Graffenstaden, France; [Doersam, Bastian] Philipps Univ, Ctr Tumor Biol & Immunol, Clin Hematol Oncol & Immunol, Expt Tumor Res, D-35043 Marburg, Germany		Fahrer, J (corresponding author), Univ Med Ctr Mainz, Dept Toxicol, D-55131 Mainz, Germany.; Fahrer, J (corresponding author), Justus Liebig Univ Giessen, Rudolf Buchheim Inst Pharmacol, D-35392 Giessen, Germany.	Joerg.Fahrer@pharma.med.uni-giessen.de	Mangerich, Aswin/K-1197-2019; Kaina, Bernd/AAE-4692-2020; Roukos, Vassilis/AAC-4827-2020; McKeague, Maureen/AAP-4667-2020	Mangerich, Aswin/0000-0001-9742-2338; Dantzer, Francoise/0000-0003-0945-8483; Seiwert, Nina/0000-0003-2169-3670; Roukos, Vassilis/0000-0002-5065-3937; , Markus/0000-0003-2490-9131; McKeague, Maureen/0000-0002-3750-6027	University Medical Center, Mainz (MAIFOR); German Research FoundationGerman Research Foundation (DFG) [DFG-FA1034/3-1, DFG-KA724/29-1, INST 38/537-1]; UCT (Universitaeres Centrum fuer Tumorerkrankungen) Mainz	We thank Dr. Alexander Burkle (University of Konstanz) for the kind gift of PARP-1 and PAR antibodies, Dr. Leona D. Samson (Massachusetts Institute of Technology) for providing MGMT knockout animals, and Dr. Shana J Sturla (ETH Zurich) for providing support with mass spectrometry-based O<SUP>6</SUP>-MeG analysis. This work was supported by the University Medical Center, Mainz (MAIFOR), and the German Research Foundation (DFG-FA1034/3-1, DFG-KA724/29-1, and INST 38/537-1). S.F. was supported by a TransMed Fellowship of the UCT (Universitaeres Centrum fuer Tumorerkrankungen) Mainz. Tissue samples were provided by the tissue bank of the University Medical Center, Mainz, in accordance with the regulations of the tissue bank.	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Natl. Acad. Sci. U. S. A.	APR 24	2018	115	17					E4061	E4070		10.1073/pnas.1712345115			10	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	GD7MZ	WOS:000430697500026	29632181	Green Published			2022-04-25	
J	Guan, YJ; Wang, YF; Li, B; Shen, K; Li, QF; Ni, YY; Huang, L				Guan, Yanjie; Wang, Yifei; Li, Bo; Shen, Kai; Li, Quanfu; Ni, Yingyin; Huang, Lei			Mitophagy in carcinogenesis, drug resistance and anticancer therapeutics	CANCER CELL INTERNATIONAL			English	Review						Mitophagy; Mechanism; Carcinogenesis; Drug resistance; Anticancer therapeutics	SELECTIVE MITOCHONDRIAL AUTOPHAGY; COLORECTAL-CANCER; OXIDATIVE-PHOSPHORYLATION; BNIP3 PROTEIN; PARKIN; PINK1; NIX; APOPTOSIS; CELLS; MUTATIONS	The mitochondrion is an organelle that plays a vital role in energy production, cytoplasmic protein degradation and cell death. Mitophagy is an autophagic procedure that specifically clears damaged mitochondria and maintains its homeostasis. Emerging evidence indicates that mitophagy is involved in many physiological processes, including cellular homeostasis, cellular differentiation and nerve protection. In this review, we describe the regulatory mechanisms of mitophagy in mammals and yeasts and highlight the recent advances relevant to its function in carcinogenesis and drug resistance. Finally, a section has been dedicated to describing the role of mitophagy in anticancer therapeutics, which is a new frontier that offers a precise and promising strategy.	[Guan, Yanjie; Wang, Yifei; Li, Bo; Shen, Kai; Li, Quanfu; Ni, Yingyin; Huang, Lei] Shanghai Jiao Tong Univ, Dept Histoembryol Genet & Dev Biol, Key Lab Cell Differentiat & Apoptosis,Sch Med, Chinese Minist Educ,Shanghai Key Lab Reprod Med, 280 South Chongqing Rd, Shanghai 200025, Peoples R China; [Li, Quanfu; Ni, Yingyin; Huang, Lei] Innovat Res Team High Level Local Univ Shanghai, Shanghai, Peoples R China		Ni, YY; Huang, L (corresponding author), Shanghai Jiao Tong Univ, Dept Histoembryol Genet & Dev Biol, Key Lab Cell Differentiat & Apoptosis,Sch Med, Chinese Minist Educ,Shanghai Key Lab Reprod Med, 280 South Chongqing Rd, Shanghai 200025, Peoples R China.; Ni, YY; Huang, L (corresponding author), Innovat Res Team High Level Local Univ Shanghai, Shanghai, Peoples R China.	niyingyin@126.com; leihuang@shsmu.edu.cn		Huang, Lei/0000-0002-4851-4807	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [82073111, 81874197]; Science and Technology Commission of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [21S11901600]	The authors acknowledge financial support from National Natural Science Foundation of China (Grant Numbers 82073111, 81874197) and Science and Technology Commission of Shanghai Municipality (Grant Number 21S11901600) to L.H.	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JUL 5	2021	21	1							350	10.1186/s12935-021-02065-w			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	TI0HN	WOS:000672462300004	34225732	gold, Green Published			2022-04-25	
J	Mbaveng, AT; Damen, F; Guefack, MGF; Tankeo, SB; Abdelfatah, S; Bitchagno, GTM; Celik, I; Kuete, V; Efferth, T				Mbaveng, Armelle T.; Damen, Francois; Guefack, Michel-Gael F.; Tankeo, Simplice Beaudelaire; Abdelfatah, Sara; Bitchagno, Gabin T. M.; Celik, Ilhami; Kuete, Victor; Efferth, Thomas			8,8-bis-(Dihydroconiferyl)-diferulate displayed impressive cytotoxicity towards a panel of human and animal cancer cells	PHYTOMEDICINE			English	Article						8, 8-bis-(dihydroconiferyl)-diferulate; Diferulic acid; Cell death; Multi-drug resistance; Natural product	BREAST-CANCER; MULTIDRUG-RESISTANCE; MEDICINAL-PLANTS; FERULIC ACID; MODES; TRANSPORTER; FERROPTOSIS; FLAVONOIDS; DEATH	Background: Recalcitrant cancers appear as a major obstacle to chemotherapy, prompting scientists to intensify the search for novel drugs to tackle the cell lines expressing multi-drug resistant (MDR) phenotypes. Purpose: The purpose of this study was to evaluate the antiproliferative potential of a ferrulic acid derivative, 8,8-bis-(dihydroconiferyl)-diferulate (DHCF2) on a panel of 18 cancer cell lines, including various sensitive and drug-resistant phenotypes, belonging to human and animals. The mode of induction of cell death by this compound was further studied. Methods: The antiproliferative activity, autophagy, ferroptotic and necroptotic cell death were evaluated by the resazurin reduction assay (RRA). CCRF-CEM leukemia cells were used for all mechanistic studies. A caspase-Glo assay was applied to evaluate the activity of caspases. Cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA) were assessed by flow cytometry. Results: DHCF2 demonstrated impressive cytotoxic effects towards the 18 cancer cell lines tested, with IC50, values all below 6.5 mu M. The obtained IC50 values were in the range of 1.17 mu M (towards CCRF-CEM leukemia cells) to 6.34 mu M (towards drug-resistant HCT116 p53(-/- )human colon adenocarcinoma cells) for DHCF2 and from 0.02 mu M (against CCRF-CEM cells) to 122.96 mu M (against multidrug-resistant CEM/ADR5000 leukemia cells) for the reference drug, doxorubicin. DHCF2 had IC50, values lower than those of doxorubicin, against CEM/ADR5000 cells and on some melanoma cell lines, such as MaMel-80a cells, Mel-2a cells, MV3 cells and SKMel-505 cells. DHCF2 induced autophagy as well as apoptosis in CCRF-CEM cells though caspases activation, MMP alteration and increase of ROS production. Conclusion: The studied diferulic acid, DHCF2, is a promising antiproliferative compound. It deserves further indepth investigations with the ultimate aim to develop a novel drug to fight cancer drug resistance.	[Mbaveng, Armelle T.; Tankeo, Simplice Beaudelaire; Abdelfatah, Sara; Kuete, Victor; Efferth, Thomas] Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, Dept Pharmaceut Biol, Staudinger Weg 5, D-55128 Mainz, Germany; [Mbaveng, Armelle T.; Guefack, Michel-Gael F.; Tankeo, Simplice Beaudelaire; Kuete, Victor] Univ Dschang, Fac Sci, Dept Biochem, POB 67, Dschang, Cameroon; [Damen, Francois; Bitchagno, Gabin T. M.] Univ Dschang, Fac Sci, Dept Chem, POB 67, Dschang, Cameroon; [Celik, Ilhami] Eskisehir Tech Univ, Fac Sci, Dept Chem, TR-26470 Eskisehir, Turkey		Efferth, T (corresponding author), Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, Dept Pharmaceut Biol, Staudinger Weg 5, D-55128 Mainz, Germany.; Kuete, V (corresponding author), POB 1499, Bafoussam, Cameroon.	kuetevictor@yahoo.fr; efferth@uni-mainz.de	Mbahbou, Gabin T. Bitchagno/AAE-3745-2021; Bitchagno, Gabin/AAN-2538-2020	Bitchagno Mbahbou, Gabin Thierry/0000-0001-5506-451X; Kuete, Victor/0000-0002-1070-1236; Mbaveng, Armelle/0000-0003-4178-4967; Abdelfatah, Sara/0000-0002-9186-2516	Alexander von Humboldt FoundationAlexander von Humboldt Foundation; Scientific Research Projects Commission of Anadolu University, Eskisehir, Turkey [1306F110]	ATM is thankful to Alexander von Humboldt Foundation for an 18 months fellowship in Prof. Dr. Thomas Efferth's laboratory in Mainz, Germany through the ''Georg Foster Research Fellowship for Experienced Researcher'' program. VK and SBT are very grateful to the Alexander von Humboldt Foundation for the 6 months further research stay fellowship in Mainz. Authors are also thankful to the Institute of Molecular Biology gGmbH (IMB) (Mainz, Germany), where the flow cytometry measurements of MMP were performed. Authors acknowledge the Scientific Research Projects Commission of Anadolu University, Eskisehir, Turkey for the funding grant (1306F110).	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J	Ni, BB; Shen, H; Wang, W; Lu, H; Jiang, LS				Ni, Binbin; Shen, Hao; Wang, Wei; Lu, Hua; Jiang, Leisheng			TGF-beta 1 reduces the oxidative stress-induced autophagy and apoptosis in rat annulus fibrosus cells through the ERK signaling pathway	JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH			English	Article						Hydrogen peroxide; Autophagy; Apoptosis; ERK; Annulus fibrosus cells; Glutathion peroxidase-1; Intervertebral disc degeneration	NUCLEUS PULPOSUS CELLS; COLON-CANCER CELLS; DEPENDENT APOPTOSIS; CELLULAR SENESCENCE; CROSS-TALK; IN-VITRO; MITOCHONDRIAL; DEATH; INVOLVEMENT; ACTIVATION	BackgroundThe aim of this study is to explore the effects of TGF-beta 1 on autophagy and apoptosis induced by exogenous hydrogen peroxide (H2O2) in annulus fibrosus (AF) cells and possible signal pathways involved in this process.MethodsAF cells were isolated from rat lumbar discs and subjected to different concentrations of exogenous H2O2 (50, 100, 200 mu mol/L) for different time periods (0.5, 1, 2, and 4h). Cell viability was determined by CCK-8 assay, and the levels of autophagy and apoptosis were evaluated by Western blotting and caspase 3, 8, 9 activity assay. By administration with different concentrations of TGF-beta 1 (5, 10, 20ng/mL), the effects of TGF-beta 1 on autophagy and apoptosis induced by H2O2 were observed, and the possible signaling pathways were also investigated by using various apoptosis inhibitors or an autophagy inhibitor Bafilomycin A (Baf A) in AF cells.ResultsH(2)O(2) significantly impaired cell viability in a dose- and time-dependent manner. H2O2 also induced a sudden and the highest level of autophagy at 1h, and gradually increased apoptosis through ERK pathway. The mitochondrial pathway was involved in H2O2-induced apoptosis in AF cells. TGF-beta 1 reduced the expression of p-ERK and downregulated the expressions of Beclin-1, LC3 II/I, and mitochondrial-related apoptotic proteins (Bax/Bcl-2, caspase-9). Meanwhile, TGF-beta 1 downregulated the level of intracellular H2O2 through upregulating the expression level of glutathione peroxidase-1 (GPx-1).ConclusionsTGF-beta 1 reduced autophagy and apoptosis induced by exogenous H2O2 through downregulating the expression of ERK in AF cells. TGF-beta 1 could downregulate the level of ERK and intracellular H2O2 by upregulating GPx-1.	[Ni, Binbin; Shen, Hao; Wang, Wei; Lu, Hua; Jiang, Leisheng] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Orthopaed Surg, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China		Lu, H; Jiang, LS (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Orthopaed Surg, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China.	luhua@xinhuamed.com.cn; jiangleisheng@xinhuamed.com.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81171757]	This work was supported by the National Natural Science Foundation of China (No. 81171757).	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Orthop. Surg. Res.	JUL 29	2019	14								241	10.1186/s13018-019-1260-4			13	Orthopedics	Science Citation Index Expanded (SCI-EXPANDED)	Orthopedics	IM3ML	WOS:000477897200003	31358027	gold, Green Published			2022-04-25	
J	Huang, YC; Yu, HS; Chai, CY				Huang, Ya-Chun; Yu, Hsin-Su; Chai, Chee-Yin			Roles of oxidative stress and the ERK1/2, PTEN and p70S6K signaling pathways in arsenite-induced autophagy	TOXICOLOGY LETTERS			English	Article						Arsenite; Oxidative stress; Autophagy; p70S6K; ERK1/2	ACTIVATING TRANSCRIPTION FACTOR; HUMAN NEUROBLASTOMA-CELLS; COLON-CANCER CELLS; DNA-DAMAGE; S6 KINASE; C-JUN; EXPRESSION; PROTEIN; INHIBITION; REPAIR	Studies show that arsenite induces oxidative stress and modifies cellular function via phosphorylation of proteins and inhibition of DNA repair enzymes. Autophagy, which has multiple physiological and pathological roles in cellular function, is initiated by oxidative stress and is regulated by the signaling pathways of phosphatidylinositol 3-phosphate kinase (PI3K)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K) and extracellular signaling-regulated protein kinase 1/2 (ERK1/2) that play important roles in oncogenesis. However, the effects of arsenite-induced oxidative stress on autophagy and on expression of related proteins are not fully understood. This study found that cells treated with sodium arsenite had reduced 8-oxoguanine DNA glycosylase 1 (OGG1) and increased 8-hydroxy-20deoxyguanosine (8-OHdG) and activating transcription factor (ATF) 3 in SV-40 immortalized human uroepithelial (SV-HUC-1) cells. Arsenite also increased the number of autophagosomes and increased levels of the autophagy markers Beclin-1 and microtubule-associated protein 1 light chain 3B. Reactive oxygen species scavenger decreased arsenite-induced autophagy in SV-HUC-1 cells. Our previous work showed that arsenite induced phosphorylation of the ERK1/2 signaling pathway. The current study further showed that arsenite decreased phosphatase and tensin homologue (PTEN) levels and increased phospho-p70S6 kinase (p-p70S6K) in SV-HUC-1 cells. However, both kinase inhibitor U0126 and the DNA (cytosine-5-)-methyltransferase 1 (DNMT1) inhibitor 5-aza-deoxycytidine abolished the effect of arsenite on expressions of PTEN and p-p70S6K. These results show that autophagy induced by arsenite exposure is mediated by oxidative stress, which regulates activation of the PTEN, p70S6K and ERK1/2 signaling pathways. Thus, this study clarifies the role of autophagy in arsenite-induced urothelial carcinogenesis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.	[Huang, Ya-Chun; Chai, Chee-Yin] Kaohsiung Med Univ, Dept Pathol, Coll Med, Kaohsiung, Taiwan; [Yu, Hsin-Su] Kaohsiung Med Univ, Dept Dermatol, Coll Med, Kaohsiung, Taiwan; [Yu, Hsin-Su] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Dermatol, Kaohsiung, Taiwan; [Chai, Chee-Yin] Kaohsiung Med Univ, Grad Inst Med, Coll Med, Kaohsiung, Taiwan; [Chai, Chee-Yin] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Pathol, Kaohsiung, Taiwan; [Chai, Chee-Yin] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 80424, Taiwan		Chai, CY (corresponding author), Kaohsiung Med Univ Hospital, Dept Pathol, 100,Tzyou 1st Rd, Kaohsiung 807, Taiwan.	cychai@kmu.edu.tw		Chai, Chee-Yin/0000-0003-0486-9742	Ministry of Science and Technology, TaiwanMinistry of Science and Technology, Taiwan [NSC101-2320-B-037-026-MY 3]; Kaohsiung Medical University Hospital, Kaohsiung, Taiwan [KMUH103-3R65]	This work was supported by a research grants from the Ministry of Science and Technology, Taiwan (NSC101-2320-B-037-026-MY 3), and Kaohsiung Medical University Hospital, Kaohsiung, Taiwan (KMUH103-3R65).	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J	Shi, L; Yan, H; An, SX; Shen, MQ; Jia, WZ; Zhang, RX; Zhao, L; Huang, G; Liu, JJ				Shi, Liang; Yan, Hui; An, Shuxian; Shen, Mengqin; Jia, Wenzhi; Zhang, Ruixue; Zhao, Li; Huang, Gang; Liu, Jianjun			SIRT5-mediated deacetylation of LDHB promotes autophagy and tumorigenesis in colorectal cancer	MOLECULAR ONCOLOGY			English	Article						autophagy; colorectal cancer; deacetylation; lactate dehydrogenase B; sirtuin 5	CELLULAR-METABOLISM; SIRT5 DEACETYLATES; PROTEIN; MITOCHONDRIAL; DESUCCINYLATION; CELLS; MALONYLATION; ACETYLATION; DEGRADATION; CONTRIBUTES	Lactate dehydrogenase B (LDHB) is a glycolytic enzyme that catalyses the conversion of lactate and NAD(+) to pyruvate, NADH and H+. Protons (H+) generated by LDHB promote lysosomal acidification and autophagy in cancer, but how this role is regulated has not been defined. In this study, we identified an important post-translational mechanism by which LDHB is regulated during autophagy in cancer cells. Mass spectrometry revealed that protein sirtuin 5 (SIRT5) is a binding partner of LDHB that deacetylated LDHB at lysine-329, thereby promoting its enzymatic activity. Deacetylated LDHB increased autophagy and accelerated the growth of colorectal cancer (CRC) cells. Notably, SIRT5 knockout or inhibition by GW5074 increased LDHB acetylation at K329 and inhibited LDHB activity, which downregulated autophagy and CRC cell growth in vitro and in vivo. Clinically, the LDHB-Ac-K329 staining score in CRC tissues was lower than that in corresponding peritumour tissues. Low LDHB-Ac-K329 status was associated with malignant progression of human CRC and served as a potential prognostic indicator for patients with CRC. Altogether, we conclude that SIRT5-induced deacetylation of LDHB triggers hyperactivation of autophagy, a key event in tumorigenesis. Thus, the SIRT5/LDHB pathway may represent a novel target for treating CRC.	[Shi, Liang; Yan, Hui; An, Shuxian; Shen, Mengqin; Jia, Wenzhi; Zhang, Ruixue; Zhao, Li; Huang, Gang; Liu, Jianjun] Shanghai Jiao Tong Univ, Dept Nucl Med, Renji Hosp, Sch Med, 1630 Dongfang Rd, Shanghai 200127, Peoples R China; [Huang, Gang] Shanghai Univ Med & Hlth Sci, Dept Canc Metab, Shanghai, Peoples R China		Huang, G; Liu, JJ (corresponding author), Shanghai Jiao Tong Univ, Dept Nucl Med, Renji Hosp, Sch Med, 1630 Dongfang Rd, Shanghai 200127, Peoples R China.	huanggang0710@126.com; ljjtbno@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81771858, 81471687, 81530053, 81471685]	The authors thank Dr Chaoming Mao (Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University) for technical assistance with mature autolysosome abundance analysis by the mRFP-EGFP-LC3 reporter. Funding was provided by the National Natural Science Foundation of China (Nos. 81771858, 81471687, 81530053 and 81471685).	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Oncol.	FEB	2019	13	2					358	375		10.1002/1878-0261.12408			18	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	HK2NA	WOS:000457747900015	30443978	gold, Green Published			2022-04-25	
J	Sun, W; Li, JL; Zhou, LK; Han, JY; Liu, R; Zhang, HY; Ning, T; Gao, ZY; Liu, BR; Chen, X; Ba, Y				Sun, Wu; Li, Jialu; Zhou, Likun; Han, Jiayi; Liu, Rui; Zhang, Haiyang; Ning, Tao; Gao, Zhiying; Liu, Baorui; Chen, Xi; Ba, Yi			The c-Myc/miR-27b-3p/ATG10 regulatory axis regulates chemoresistance in colorectal cancer	THERANOSTICS			English	Article						miR-27b-3p; ATG10; chemoresistance; colorectal cancer; autophagy	TUMOR PROGRESSION; AUTOPHAGY; PROLIFERATION; CELLS; MICRORNAS; TARGET	Oxaliplatin (OXA) resistance is the major obstacle to the anticancer effects of chemotherapy in colorectal cancer (CRC) patients. MicroRNAs (miRNAs) play an important role in the chemoresistance of various tumors. Our objective is to clarify the underlying mechanism of miRNAs in chemoresistance and provide a potential strategy to improve the response of CRC patients to chemotherapeutics. Methods: MiRNA microarray and Real-time PCR were performed to compare changes in miRNA expression between oxaliplatin-resistant and the parental cells. CCK8, apoptosis assay, immunofluorescence and xenograft studies were used to elucidate the impact of miR-27b-3p on regulating chemoresistance. Luciferase reporter assay and western blot were carried to assess the regulatory role of miR-27b-3p in ATG10 expression. The effects of miR-27b-3p and ATG10 on autophagy were investigated by GFP-LC3 fluorescence microscopy, transmission electron microscopy, and western blot. ChIP assay and luciferase assay were performed to test the c-Myc's occupancy on the miR-27B promoter. Results: We observed that miR-27b-3p expression was significantly downregulated in oxaliplatin-resistant cell lines (SW480-OxR and HCT116-OxR) compared to the corresponding parental cell lines and that miR-27b-3p expression was positively correlated with disease-free survival (DFS) time in colorectal cancer patients. MiR-27b-3p could sensitize colorectal cancer cells to oxaliplatin in vitro and in vivo. Under oxaliplatin treatment, chemoresistant cells showed a higher autophagy level than parental cells. Moreover, we also identified that miR-27b-3p inhibited the expression of ATG10 at the posttranscriptional level, thus inhibiting autophagy. Further study demonstrated that c-Myc can inhibit the expression of miR-27b-3p via binding to the promoter region of miR-27B gene. Conclusions: Our study identifies a novel c-Myc/miR-27b-3p/ATG10 signaling pathway that regulates colorectal cancer chemoresistance. These results suggest that miR-27b-3p is not only a potential indicator for evaluating efficiency of chemotherapy, but also a valuable therapeutic target for CRC, especially for patients with chemoresistance.	[Sun, Wu; Zhou, Likun; Han, Jiayi; Liu, Rui; Zhang, Haiyang; Ning, Tao; Ba, Yi] Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Tianjins Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Huan Hu Xi Rd 18, Tianjin 300060, Peoples R China; [Li, Jialu] Shanghai Jiao Tong Univ, Shanghai Inst Digest Dis,Div Gastroenterol & Hepa, Sch Med,Key Lab Gastroenterol & Hepatol,Minist Hl, Renji Hosp,State Key Lab Oncogenes & Related Gene, Shanghai, Peoples R China; [Gao, Zhiying; Chen, Xi] Nanjing Univ, NAILS, Jiangsu Engn Res Ctr MicroRNA Biol & Biotechnol, State Key Lab Pharmaceut Biotechnol,Sch Life Sci, Xianlin Rd 163, Nanjing 210046, Jiangsu, Peoples R China; [Liu, Baorui] Nanjing Univ, Comprehens Canc Ctr, Drum Tower Hosp, Med Sch, Zhognshan Rd 321, Nanjing 210008, Jiangsu, Peoples R China; [Liu, Baorui] Nanjing Univ, Clin Canc Inst, Zhognshan Rd 321, Nanjing 210008, Jiangsu, Peoples R China		Ba, Y (corresponding author), Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Tianjins Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Huan Hu Xi Rd 18, Tianjin 300060, Peoples R China.; Chen, X (corresponding author), Nanjing Univ, NAILS, Jiangsu Engn Res Ctr MicroRNA Biol & Biotechnol, State Key Lab Pharmaceut Biotechnol,Sch Life Sci, Xianlin Rd 163, Nanjing 210046, Jiangsu, Peoples R China.; Liu, BR (corresponding author), Nanjing Univ, Comprehens Canc Ctr, Drum Tower Hosp, Med Sch, Zhognshan Rd 321, Nanjing 210008, Jiangsu, Peoples R China.; Liu, BR (corresponding author), Nanjing Univ, Clin Canc Inst, Zhognshan Rd 321, Nanjing 210008, Jiangsu, Peoples R China.	baoruiliu07@163.com; xichen@nju.edu.cn; bayi@tjmuch.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [8170243, 81772629, 81602158, 81602156, 81702275, 81802363, 81702431, 81702437, 81772843]; Demonstrative Research Platform of Clinical Evaluation Technology for New Anticancer Drugs [2018ZX09201015]; Tianjin Science FoundationNatural Science Foundation of Tianjin [18JCQNJC81900, 18JCYBJC92000, 18JCYBJC25400, 16PTSYJC00170, 18JCYBJC92900]; Science & Technology Development Fund of the Tianjin Education Commission for Higher Education [2018KJ046, 2017KJ227, 2017KJ204]	This work was supported by grants from the National Natural Science Foundation of China (Nos. 8170243, 81772629, 81602158, 81602156, 81702275, 81802363, 81702431, 81702437, 81772843) and the Demonstrative Research Platform of Clinical Evaluation Technology for New Anticancer Drugs (No. 2018ZX09201015). This work was also supported by the Tianjin Science Foundation (Nos. 18JCQNJC81900, 18JCYBJC92000, 18JCYBJC25400, 16PTSYJC00170, 18JCYBJC92900) and the Science & Technology Development Fund of the Tianjin Education Commission for Higher Education (2018KJ046, 2017KJ227, 2017KJ204). The funders had no role in the study design, the data collection and analysis, the interpretation of the data, the writing of the report, and the decision to submit this article for publication.	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J	Wang, WC; Zhang, R; Wang, JX; Tang, J; Wang, MG; Kuang, Y				Wang, Wencong; Zhang, Rui; Wang, Jinxing; Tang, Jun; Wang, Mingan; Kuang, Yu			Antitumour Activity of Muricatacin Isomers and its Derivatives in Human Colorectal Carcinoma Cell HCT116	ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY			English	Article						Muricatacin; antitumour activity; colorectal carcinoma cell line HCT116; cell cycle arrest; apoptosis; autophagy	P53; 6-ACETOXY-5-HEXADECANOLIDE; ACETOGENINS; RESISTANCE; ARREST	Background and Purpose: Colorectal cancer is one of the leading causes of cancer-related death in elderly people. The natural product muricatacin is an important member of the gamma-lactone family, and it has exhibited antitumour activity in multiple cancer cell lines; however, the antitumour activities of muricatacin stereoisomers and their derivatives in colorectal cancer cells have not yet been systematically explored. Methods: The colorectal carcinoma cell line HCT116 was investigated in this study. Cell proliferation was assessed by MTT assay or crystal violet staining. Cell cycle arrest and cell apoptosis were evaluated by flow cytometry assay. The expression levels of p53, p21, cyclin E, cyclin D1, caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9 and LC3B were measured using western blot analysis. Autophagy induced by M2 was monitored by immunofluorescence assay with an antibody against LC3B. Results: Cell proliferation assays showed that both naturally occurring muricatacin (M4) and its synthetic stereoisomer (M2) are potent cell growth inhibitors in HCT116 cells, with IC50 values of 79.43 and 83.17 mu M, respectively; these values are much lower than those of the other two isomers, M1 and M3, and those of the six-membered lactone analogues. The flow cytometry analysis revealed that M2 and M4 induced significant cell cycle arrest during G(0)/G(1) phase and caused relatively low apoptosis rates in HCT1 16 cells. Further analysis indicated that M2 caused p53-independent p21 induction and cyclin E/cyclin D1 downregulation. In addition, M2 also markedly induced autophagy in the early stage of administration. Conclusion: Our results suggested that muricatacins possess potent antitumour activity against the colorectal carcinoma cell tine HCT116 through inducing G(0)/G(1) phase cell cycle arrest and autophagy in the early stage of administration.	[Wang, Wencong; Zhang, Rui; Wang, Jinxing; Tang, Jun; Kuang, Yu] China Agr Univ, Coll Vet Med, Dept Basic Vet Med, Beijing 100193, Peoples R China; [Wang, Mingan] China Agr Univ, Coll Sci, Dept Appl Chem, Beijing 100193, Peoples R China		Kuang, Y (corresponding author), Fac China Agr Univ, Dept Basic Vet Med, POB 100193, Beijing, Peoples R China.	kuangyu@cau.edu.cn		Zhang, Rui/0000-0001-9015-0819	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21172254, 31500703]	The research was supported by the National Natural Science Foundation of China (No. 21172254 and 31500703).	AGARWAL ML, 1995, P NATL ACAD SCI USA, V92, P8493, DOI 10.1073/pnas.92.18.8493; Alali FQ, 1999, J NAT PROD, V62, P504, DOI 10.1021/np980406d; Amaral JD, 2010, DISCOV MED, V9, P145; Ando Kosei, 2013, Cancers (Basel), V5, P591, DOI 10.3390/cancers5020591; Asghar U, 2015, NAT REV DRUG DISCOV, V14, P130, DOI 10.1038/nrd4504; Bonni A, 1999, SCIENCE, V286, P1358, DOI 10.1126/science.286.5443.1358; Chaudhari DA, 2016, TETRAHEDRON-ASYMMETR, V27, P114, DOI 10.1016/j.tetasy.2016.01.003; Chikara S, 2017, NUTR CANCER, V69, P652, DOI 10.1080/01635581.2017.1296169; Cooze C, 2017, SYNLETT, V28, P2928, DOI 10.1055/s-0036-1590858; DONG HB, 2015, CHINESE J ORG CHEM, V35, P152, DOI DOI 10.6023/CJOC201408035; Dong HB, 2014, J ASIAN NAT PROD RES, V16, P847, DOI 10.1080/10286020.2014.916695; Dong HB, 2014, TETRAHEDRON-ASYMMETR, V25, P610, DOI 10.1016/j.tetasy.2014.03.006; Ferlay J, 2010, INT J CANCER, V127, P2893, DOI 10.1002/ijc.25516; Freed-Pastor WA, 2012, GENE DEV, V26, P1268, DOI 10.1101/gad.190678.112; Geng YY, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0128928; Lane DP, 2010, CSH PERSPECT BIOL, V2, DOI 10.1101/cshperspect.a001222; Liang XJ, 2010, METHODS MOL BIOL, V596, P467, DOI 10.1007/978-1-60761-416-6_21; Liaw CC, 2016, PROG CHEM ORG NAT PR, V101, P113, DOI 10.1007/978-3-319-22692-7_2; Makabe Hidefumi, 2008, Curr Drug Discov Technol, V5, P213, DOI 10.2174/157016308785739820; Martin LA, 2003, J BIOL CHEM, V278, P30458, DOI 10.1074/jbc.M305226200; Murcia MC, 2010, CURR ORG CHEM, V14, P15, DOI 10.2174/138527210790226410; Natarajan Balasubramanian, 2013, Worm, V2, pe24059, DOI 10.4161/worm.24059; Rebucci M, 2013, BIOCHEM PHARMACOL, V85, P1219, DOI 10.1016/j.bcp.2013.02.017; Romer L, 2006, ANGEW CHEM INT EDIT, V45, P6440, DOI 10.1002/anie.200600611; Santarpia L, 2012, EXPERT OPIN THER TAR, V16, P103, DOI 10.1517/14728222.2011.645805; Sherr CJ, 1996, SCIENCE, V274, P1672, DOI 10.1126/science.274.5293.1672; Wei JX, 2012, J NUCLEIC ACIDS, V2012, DOI 10.1155/2012/687359; Zhang R, 2017, J VIROL, V91, DOI [10.1128/JVI.01148-17, 10.1128/jvi.01148-17]	28	0	0	3	14	BENTHAM SCIENCE PUBL LTD	SHARJAH	EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES	1871-5206	1875-5992		ANTI-CANCER AGENT ME	Anti-Cancer Agents Med. Chem.		2020	20	2					254	263		10.2174/1871520619666191115111032			10	Oncology; Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	LI9NX	WOS:000529804200004	31729294				2022-04-25	
J	Zhang, L; Rong, Y; Zheng, J; Yang, CL; Chen, YZ; Wang, J; Wei, G				Zhang, Lei; Rong, Ying; Zheng, Jie; Yang, Chengli; Chen, Yongzheng; Wang, Jing; Wei, Gang			Design, synthesis and biological evaluation of novel nitric oxide-donating podophyllotoxin derivatives as potential antiproliferative agents against multi-drug resistant leukemia cells	RSC ADVANCES			English	Article							ANTI-MDR AGENTS; COLON-CANCER CELLS; ANTITUMOR AGENTS; SIGNALING PATHWAYS; IN-VITRO; AUTOPHAGY; CHEMOTHERAPY; DOXORUBICIN; APOPTOSIS; CYTOTOXICITY	Multidrug resistance remains a major obstacle for the effective treatment of carcinoma. To find new drugs for the chemotherapy of drug-resistant leukemia, in this study, two novel nitric oxide-donating podophyllotoxin derivatives were synthesized and preliminarily evaluated in vitro. Biological evaluation indicated that the more active molecule, S1, enhanced the intracellular NO level and significantly inhibited the proliferation of drug-resistant K562/VCR and K562/ADR cells with IC50 values of 0.008 +/- 0.001 and 0.007 +/- 0.001 mu M, respectively, which were similar to that of sensitive K562 cells. Furthermore, it was observed that S1 blocked the G2 phase of the K562/ADR cell cycle by disruption of the microtubule organization and inhibition of CDK1 and CDK2 expression. Meanwhile, S1 induced apoptosis of K562/ADR cells via mitochondrial depolarization and activation of caspase-3. In addition, S1 suppressed the P-gp expression, induced autophagy by regulation of Beclin1 and LC3-II, and inhibited the mTOR and STAT3 signaling in K562/ADR cells. Overall, S1 may be a promising candidate against drug-resistant leukemia.	[Zhang, Lei; Yang, Chengli; Chen, Yongzheng; Wang, Jing] Zunyi Med Univ, Green Pharmaceut Engn Res Ctr Guizhou Prov, Gener Drug Res Ctr Guizhou Prov, Sch Pharm, Zunyi 563003, Peoples R China; [Rong, Ying] Zunyi Med Univ, Affiliated Hosp, Dept Pediat 2, Zunyi 563003, Peoples R China; [Zheng, Jie] Zunyi Med Univ, Affiliated Hosp, Dept Nephrol & Rheumatol, Zunyi 563003, Peoples R China; [Wei, Gang] CSIRO Mfg, POB 218, Lindfield, NSW 2070, Australia		Zhang, L; Wang, J (corresponding author), Zunyi Med Univ, Green Pharmaceut Engn Res Ctr Guizhou Prov, Gener Drug Res Ctr Guizhou Prov, Sch Pharm, Zunyi 563003, Peoples R China.; Wei, G (corresponding author), CSIRO Mfg, POB 218, Lindfield, NSW 2070, Australia.	lzhang@zmc.edu.cn; wangjing@zmc.edu.cn; gang.wei@csiro.au			Ministry of Education "Chunhui Project" Foundation of China [Z2015008]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81860622]; Department of Science and Technology of Guizhou ProvinceDepartment of Science & Technology (DOST), PhilippinesDepartment of Science & Technology (India) [[2017]1219]; Joint Fund of the Department of Science and Technology of Zunyi City and Zunyi Medical University [[2018]27]; National First-Rate Construction Discipline of Guizhou Province (Pharmacy) [YLXKJS-YX-04]	This work was supported by Ministry of Education "Chunhui Project" Foundation of China (No. Z2015008), National Natural Science Foundation of China (No. 81860622), Department of Science and Technology of Guizhou Province (No. [2017]1219), Joint Fund of the Department of Science and Technology of Zunyi City and Zunyi Medical University ([2018]27) and National First-Rate Construction Discipline of Guizhou Province (Pharmacy) (YLXKJS-YX-04).	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J	El-kott, AF; Al-kahtani, MA; Shati, AA				El-kott, Attalla Farag; Al-kahtani, Mohammed Ali; Shati, Ali A.			Calycosin induces apoptosis in adenocarcinoma HT29 cells by inducing cytotoxic autophagy mediated by SIRT1/AMPK-induced inhibition of Akt/mTOR	CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY			English	Article						AMPK; autophagy; Calycosin; colorectal cancer; mTOR; SIRT1	COLORECTAL-CANCER CELLS; ADJUVANT TREATMENT; SIRT1; FAMILY; EXPRESSION; RESISTANCE; MIGRATION; HYPOXIA; STRESS; DEATH	Autophagy promotes cell survival or induces apoptosis in cancer cells. While SIRT1 and AMPK induce autophagy in both normal and cancer cells, Akt and mTOR can inhibit it. Calycosin, a methoxyisoflavone, protects against several types of solid tumours including colorectal cancer. However, the mechanisms behind the antitumour effect of Calycosin remain largely unknown. This study investigates if autophagy mediates the anti-tumourigenesis effect afforded by Calycosin and examines if this effect involves activation of SIRT1 and/or AMPK. Human colorectal (HT29) carcinoma cells were cultured under normal conditions with Calycosin (50 mu mol/L) in the presence or absence of chloroquine (10 mu mol/L), EX-527 (100 nmol/L, SIRT1 inhibitor), or IGF-1 (100 ng/mL, Akt/mTOR activator) for 48 hours. Calycosin inhibited cell growth, proliferation and invasion and increased protein levels of Beclin-1 and LC3II, markers of autophagy. It significantly increased protein levels of cleaved caspase-3, Bax, and SIRT1, and activity of AMPK and reduced those of Bcl-2. These effects were parallel with concomitant reduction in protein levels p-src, integrin-beta 1 and Cyclin-D1 and activities of Akt and mTOR. Inhibition of autophagy by CQ reversed all these effects except cell invasion. Interestingly, co-incubating the cells with either EX-527 or IGF-1 completely prevented Calycosin-induced autophagy and all other associated effects and increased cell invasion. Also, blockade of SIRT-1 prevented the activation of AMPK, Akt, and mTOR, suggesting it to be an upstream regulator of these markers. In conclusion, Calycosin stimulates CRC cell apoptosis and inhibits their invasion by acting as SIRT1 activator which induces activation of AMPK-induced inhibition of Akt/mTOR axis.	[El-kott, Attalla Farag; Al-kahtani, Mohammed Ali; Shati, Ali A.] King Khalid Univ, Coll Sci, Biol Dept, Abha, Saudi Arabia; [El-kott, Attalla Farag] Damanhour Univ, Coll Sci, Zool Dept, Damanhour, Egypt		El-kott, AF (corresponding author), King Khalid Univ, Coll Sci, POB 9004, Abha 61413, Saudi Arabia.	elkottaf@yahoo.com	El-kott, Attalla F/D-1971-2017; El-kott, Attalla/AAW-5325-2021	El-kott, Attalla/0000-0001-5060-0790; Shati, Ali/0000-0003-1800-7238	King Khalid University [R.G.P.1/46/39]	King Khalid University, Grant/Award Number: R.G.P.1/46/39	Behrends C, 2010, NATURE, V466, P68, DOI 10.1038/nature09204; Bel S, 2018, AUTOPHAGY, V14, P719, DOI 10.1080/15548627.2018.1430462; Besio R, 2018, BBA-MOL BASIS DIS, V1864, P1642, DOI 10.1016/j.bbadis.2018.02.002; Catalano M, 2015, MOL ONCOL, V9, P1612, DOI 10.1016/j.molonc.2015.04.016; Chen J, 2013, CELL PHYSIOL BIOCHEM, V32, P1790, DOI 10.1159/000356612; Chen J, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0088232; Cheng X, 2018, CANCER LETT, V431, P105, DOI 10.1016/j.canlet.2018.05.046; Condello M, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20030725; Cory S, 2002, NAT REV CANCER, V2, P647, DOI 10.1038/nrc883; Daniels MS, 2017, J CLIN ONCOL, V35, P2588, DOI 10.1200/JCO.2017.72.7222; Denton D, 2012, CELL DEATH DIFFER, V19, P87, DOI 10.1038/cdd.2011.146; Fang ZJ, 2018, CANCER LETT, V415, P58, DOI 10.1016/j.canlet.2017.11.040; Fukuda T, 2016, ONCOL LETT, V12, P2560, DOI 10.3892/ol.2016.4978; Galluzzi L, 2015, EMBO J, V34, P856, DOI 10.15252/embj.201490784; Hu XB, 2019, AUTOPHAGY, V15, P453, DOI 10.1080/15548627.2018.1520548; Huang JX, 2009, BIOCHEM SOC T, V37, P217, DOI 10.1042/BST0370217; Huang YH, 2017, ONCOTARGET, V8, P52783, DOI 10.18632/oncotarget.17189; Jung CH, 2010, FEBS LETT, V584, P1287, DOI 10.1016/j.febslet.2010.01.017; Kang JS, 2009, TRENDS BIOCHEM SCI, V34, P491, DOI 10.1016/j.tibs.2009.06.003; Klionsky DJ, 2000, SCIENCE, V290, P1717, DOI 10.1126/science.290.5497.1717; Kroemer G, 2010, MOL CELL, V40, P280, DOI 10.1016/j.molcel.2010.09.023; Kume S, 2010, J CLIN INVEST, V120, P1043, DOI 10.1172/JCI41376; Lan F, 2008, J BIOL CHEM, V283, P27628, DOI 10.1074/jbc.M805711200; Lee IH, 2008, P NATL ACAD SCI USA, V105, P3374, DOI 10.1073/pnas.0712145105; Li J, 2009, ANN SURG ONCOL, V16, P761, DOI 10.1245/s10434-008-0260-0; Liao H, 2015, AM J CANCER RES, V5, P125; Maiuri MC, 2007, EMBO J, V26, P2527, DOI 10.1038/sj.emboj.7601689; Martinou JC, 2011, DEV CELL, V21, P92, DOI 10.1016/j.devcel.2011.06.017; Meijer AJ, 2004, INT J BIOCHEM CELL B, V36, P2445, DOI 10.1016/j.biocel.2004.02.002; Neufeld TP, 2010, CURR OPIN CELL BIOL, V22, P157, DOI 10.1016/j.ceb.2009.11.005; Nordman IC, 2006, ANZ J SURG, V76, P373, DOI 10.1111/j.1445-2197.2006.03726.x; Qomaladewi NP, 2019, J GINSENG RES, V43, P349, DOI 10.1016/j.jgr.2018.12.011; Ruderman NB, 2010, AM J PHYSIOL-ENDOC M, V298, pE751, DOI 10.1152/ajpendo.00745.2009; Schonewolf CA, 2014, WORLD J GASTRO ONCOL, V6, P74, DOI 10.4251/wjgo.v6.i3.74; Seguin L, 2015, TRENDS CELL BIOL, V25, P234, DOI 10.1016/j.tcb.2014.12.006; Shin DH, 2014, CANCER RES, V74, P298, DOI 10.1158/0008-5472.CAN-13-2620; Shroff K, 2012, LANGMUIR, V28, P1858, DOI 10.1021/la203322t; Smeby J, 2018, ANN ONCOL, V29, P1227, DOI 10.1093/annonc/mdy085; Tang JC, 2016, CHINESE MED J-PEKING, V129, P456, DOI 10.4103/0366-6999.176069; Tauriello DVF, 2017, MOL ONCOL, V11, P97, DOI 10.1002/1878-0261.12018; Thorburn A, 2008, APOPTOSIS, V13, P1, DOI 10.1007/s10495-007-0154-9; Tuloup-Minguez V, 2013, CELL CYCLE, V12, P3317, DOI 10.4161/cc.26298; Wang HY, 2013, TOXICOLOGY, V308, P104, DOI 10.1016/j.tox.2013.03.015; Williams A, 2008, NAT CHEM BIOL, V4, P295, DOI 10.1038/nchembio.79; Wils J, 2001, ANN ONCOL, V12, P13, DOI 10.1023/A:1008357725209; Yang L, 2016, MOL MED REP, V14, P4559, DOI 10.3892/mmr.2016.5818; Yu L, 2010, NATURE, V465, P942, DOI 10.1038/nature09076; Zhang DH, 2013, J CHEM-NY, V2013, DOI 10.1155/2013/946248; Zhao XG, 2016, GENE, V591, P123, DOI 10.1016/j.gene.2016.07.012; Zhou JH, 2017, ONCOL LETT, V14, P6950, DOI 10.3892/ol.2017.7090; Zhou Y, 2015, TUMOR BIOL, V36, P5333, DOI 10.1007/s13277-015-3194-8	51	18	21	1	24	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0305-1870	1440-1681		CLIN EXP PHARMACOL P	Clin. Exp. Pharmacol. Physiol.	OCT	2019	46	10					944	954		10.1111/1440-1681.13133			11	Pharmacology & Pharmacy; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy; Physiology	IY2GM	WOS:000486208400009	31276230				2022-04-25	
J	Yao, JL; Xie, JS; Xie, BB; Li, YR; Jiang, WL; Sui, XB; Zhou, XY; Pan, HM; Han, WD				Yao, Junlin; Xie, Jiansheng; Xie, Binbin; Li, Yiran; Jiang, Wiling; Sui, Xinbing; Zhou, Xiaoyun; Pan, Hongming; Han, Weidong			Therapeutic effect of hydroxychloroquine on colorectal carcinogenesis in experimental murine colitis	BIOCHEMICAL PHARMACOLOGY			English	Article						Hydroxychloroquine; Colitis-associated colorectal cancer; Macrophages; Toll-like receptor 4; Reactive oxygen species	INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE RECEPTOR-3; CANCER CELLS; REACTIVE OXYGEN; AUTOPHAGY INHIBITION; OXIDATIVE STRESS; TNF-ALPHA; CHLOROQUINE; MODEL; MICE	Chronic inflammation in the intestine is a strong risk factor for colitis-associated colorectal cancer (CAC). Hydroxychloroquine (HCQ) is widely used as an anti-inflammatory drug in the treatment of immune mediated inflammatory disorders and various tumors. However, little is known regarding the effects of HCQ on colitis-associated tumorigenesis. In this study, mice treated with HCQ showed a significant reduction in early-stage colitis following azoxymethane (AOM)/dextran sodium sulfate (DSS) administration, as well as a remarkable inhibition of colonic tumorigenesis and tumor growth at late stages of CAC. Mechanistically, the therapeutic effects of HCQ were attributed to inhibition of inflammatory responses and production of mutagenic reactive oxygen species (ROS) in immune cells and subsequent promotion of apoptosis and cell cycle arrest in tumor cells. Furthermore, we found that HCQ inhibited the production of inflammatory cytokines and ROS in response to toll-like receptor 4 (TLR4) activation in macrophages. Our data presented herein may help guide the clinical use of HCQ as a prevention and treatment strategy for CAC. (C) 2016 Elsevier Inc. All rights reserved.	[Yao, Junlin; Xie, Binbin; Li, Yiran; Jiang, Wiling; Sui, Xinbing; Pan, Hongming; Han, Weidong] Zhejiang Univ, Inst Clin Sci, Sir Run Run Shaw Hosp, Dept Med Oncol,Coll Med, Hangzhou, Zhejiang, Peoples R China; [Xie, Jiansheng; Pan, Hongming; Han, Weidong] Zhejiang Univ, Inst Clin Sci, Sir Run Run Shaw Hosp, Lab Canc Biol,Coll Med, Hangzhou, Zhejiang, Peoples R China; [Zhou, Xiaoyun] Hangzhou Xiasha Hosp, Dept Med Oncol, Hangzhou, Zhejiang, Peoples R China		Pan, HM; Han, WD (corresponding author), Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, 3 East Qinchun Rd, Hangzhou 310016, Zhejiang, Peoples R China.	hongmingpan@gmail.com; hanwd@zju.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81272593, 81572592, 81372621]; Key Projects of Natural Foundation of Zhejiang Province [LZ15H160001]; National Health and Family Planning Commission Fund [2015112271]; Zhejiang Province Preeminence Youth Fund [LR16H160001]	This work was supported by the National Natural Science Foundation of China (81272593, 81572592), the Key Projects of Natural Foundation of Zhejiang Province (LZ15H160001), and the National Health and Family Planning Commission Fund (2015112271) to H. Pan; and the National Natural Science Foundation of China (81372621) and Zhejiang Province Preeminence Youth Fund (LR16H160001) to W. Han.	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Pharmacol.	SEP 1	2016	115						51	63		10.1016/j.bcp.2016.06.004			13	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	DT5TO	WOS:000381545700006	27288548				2022-04-25	
S	Pawelek, JM; Chakraborty, AK		VandeWoude, GF; Klein, G		Pawelek, John M.; Chakraborty, Ashok K.			The Cancer Cell-Leukocyte Fusion Theory of Metastasis	ADVANCES IN CANCER RESEARCH, VOL 101	Advances in Cancer Research		English	Review; Book Chapter							N-ACETYLGLUCOSAMINYLTRANSFERASE-V; HEPATOCYTE GROWTH-FACTOR; EPITHELIAL-MESENCHYMAL TRANSITIONS; MELANOCYTE-STIMULATING HORMONE; FOCAL-ADHESION KINASE; MARROW-DERIVED CELLS; NORMAL MOUSE CELLS; FACTOR-KAPPA-B; BETA-1-6 BRANCHED OLIGOSACCHARIDES; CUTANEOUS MALIGNANT-MELANOMA	The cause of metastasis remains elusive despite vast information oil cancer cells. We posit that cancer cell fusion with microphages or other migratory bone marrow-derived cells (BMDCs) provides an explanation. BMDCs fused with tumor cells were present in animal tumor xenografts where they were associated with metastases. In myeloma patients, transcriptionally active myeloma nuclei were incorporated into osteoclasts through fusion. In patients with renal cell carcinoma arising poststem cell transplant, donor genes were incorporated in recipient cancer cell nuclei, most likely through fusion, and showed Minor distribution patterns characteristic of cancer stern cells. Melanoma-macrophage hybrids generated ill vitro contained chromosomes front both parental partners, showed increased ploidy, and transcribed and translated genes front both parents. They exhibited chemotactic migration in vitro toward fibronectin and exhibited high frequencies of metastasis when implanted in mice. They produced macromolecules that are characteristic of macrophages and known indicators of metastasis (c-Met, SPARC, MCR1, GnT-V, and the integrin subunits alpha(3), alpha(5), alpha(6), alpha(v), beta(1), beta(3)). They also produced high levels of beta 1,6-branched oligosaccharides-predictors of poor survival in patients with melanoma or carcinomas of the breast, lung, and colon. WC thus hypothesize such gene expression patterns in cancer are generated through fusion. Tumor hybrids also showed active autophagy, a characteristic of both metastatic Cancers and macrophages. BMDC-tumor cell fusion explains epidermal-mesenchymal transition in cancer since BMDCs express mesodermal traits and epithelial-mesenchymal transition regulators (Twist, SPARC, and others). If BMDC-tumor cell fusion underlies invasion and metastasis in human Cancer, new approaches for therapeutic intervention would lie mandated. (c) 2008 Elsevier Inc.	[Pawelek, John M.; Chakraborty, Ashok K.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA; [Pawelek, John M.; Chakraborty, Ashok K.] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA		Pawelek, JM (corresponding author), Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA.		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J	Wang, YF; Zhang, SY; Dang, SW; Fang, X; Liu, M				Wang, Yunfeng; Zhang, Songyan; Dang, Shuwei; Fang, Xuan; Liu, Ming			Overexpression of microRNA-216a inhibits autophagy by targeting regulated MAP1S in colorectal cancer	ONCOTARGETS AND THERAPY			English	Article						miR-216a; MAP1S; autophagy; TGF-beta; colorectal cancer	CELL-PROLIFERATION; SUPPRESSES PROLIFERATION; PROMOTES AUTOPHAGY; TUMOR INVASION; APOPTOSIS; MIGRATION; EXPRESSION	Background: Autophagy executes the rapid degradation of unneeded proteins and organelles through the lysosomal pathway, and is a crucial catabolic process widely conserved among eukaryotes. miRNAs can modulate autophagy by targeting genes encoding proteins involved in the process. A great deal of researchhas indicated that miR-216a was a functional miRNA related to tumorigenesis. However, the contribution of miR-216a to autophagy in colorectal cancer (CRC) remains unclear. The purpose of this study was to investigate the role of miR-216a in autophagy in CRC cells. Methods: The expression levels of miR-216a in 67 paired CRC patients were evaluated by qRT-PCR. Direct gene targeting predicted by TargetScan and miRanda was confirmed by luciferase activity. Western blot and flow cytometry were used to identify the regulatory mechanism of miR-216a on autophagy in CRC cells. Results: We determined that miR-216a is downregulated in CRC by screening its expression in 67 CRC tissue samples. Dual luciferase reporter assays showed that miR-216a binds the 3'-UTR of MAP1S, suggesting that MAP1S is a direct target of miR-216a. miR-216a could inhibit autophagy in HCT-116 and HT-29 CRC cells through downregulating MAP1S expression. Flow cytometry and Western blot analysis demonstrated that overexpression of miR-216a reduced MAP1S mRNA and protein levels. Moreover, we determined that miR-216a-regulated inhibition of autophagy via MAP1S regulation involves the TGF-beta pathway. Conclusion: Taken together, our findings indicate that miR-216a was a tumor-suppressor miRNA in human CRC, which can inhibit autophagy via the TGF-beta/MAP1S pathway.	[Wang, Yunfeng; Zhang, Songyan; Dang, Shuwei; Fang, Xuan; Liu, Ming] Harbin Med Univ, Affiliated Hosp 4, Dept Gen Surg, 37 Yiyuan Rd, Harbin 150001, Heilongjiang, Peoples R China		Liu, M (corresponding author), Harbin Med Univ, Affiliated Hosp 4, Dept Gen Surg, 37 Yiyuan Rd, Harbin 150001, Heilongjiang, Peoples R China.	mingliu35@hrbmu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81372612, 81302059]	This work was supported by funds from the National Natural Science Foundation of China (Grant No. 81372612 and 81302059).	Calin GA, 2006, NAT REV CANCER, V6, P857, DOI 10.1038/nrc1997; Chen D, 2015, CANCER LETT, V362, P208, DOI 10.1016/j.canlet.2015.03.041; Cheng Y, 2016, REPROD BIOL, V16, P225, DOI 10.1016/j.repbio.2016.07.002; Colombo MI, 2007, IUBMB LIFE, V59, P238, DOI 10.1080/15216540701230503; He XQ, 2012, MOL MED, V18, P1491, DOI 10.2119/molmed.2012.00304; Hu J, 2018, J PHARMACOL SCI, V136, P114, DOI 10.1016/j.jphs.2018.02.003; Hu JG, 2017, AUTOPHAGY, V13, P333, DOI 10.1080/15548627.2016.1256520; Jeong H, 2015, NANOSCALE RES LETT, V10, P1, DOI 10.1186/s11671-015-0961-9; Kiyono K, 2009, CANCER RES, V69, P8844, DOI 10.1158/0008-5472.CAN-08-4401; Levine B, 2008, CELL, V132, P27, DOI 10.1016/j.cell.2007.12.018; Li WJ, 2016, AGING CELL, V15, P370, DOI 10.1111/acel.12441; Li YJ, 2013, EXP CELL RES, V319, P1094, DOI 10.1016/j.yexcr.2013.02.002; Lum JJ, 2005, CELL, V120, P237, DOI 10.1016/j.cell.2004.11.046; Ma ZB, 2014, ASIAN PAC J CANCER P, V15, P9265, DOI 10.7314/APJCP.2014.15.21.9265; Mathew R, 2007, GENE DEV, V21, P1367, DOI 10.1101/gad.1545107; Qu XP, 2007, CELL, V128, P931, DOI 10.1016/j.cell.2006.12.044; Ren YL, 2017, CANCER LETT, V390, P126, DOI 10.1016/j.canlet.2017.01.009; Sotthibundhu A, 2016, STEM CELL RES THER, V7, DOI 10.1186/s13287-016-0425-x; Stein U, 2009, NAT MED, V15, P59, DOI 10.1038/nm.1889; World Cancer Research Fund International, 2012, WORLDW DAT; Wu YY, 2013, AUTOPHAGY, V9, P595, DOI 10.4161/auto.23641; Xiao RL, 2015, BIOMED PHARMACOTHER, V74, P138, DOI 10.1016/j.biopha.2015.08.006; Yan LK, 2017, BIOMED PHARMACOTHER, V96, P974, DOI 10.1016/j.biopha.2017.11.138; Yu Q, 2000, GENE DEV, V14, P163; Zhang DJ, 2017, INT J CANCER, V140, P2298, DOI 10.1002/ijc.30656; Zhang XL, 2015, ONCOL REP, V34, P1557, DOI 10.3892/or.2015.4078; Zhang YJ, 2017, BIOCHEM BIOPH RES CO, V483, P816, DOI 10.1016/j.bbrc.2016.12.167	27	7	8	1	1	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1178-6930			ONCOTARGETS THER	OncoTargets Ther.		2019	12						4621	4629		10.2147/OTT.S196992			9	Biotechnology & Applied Microbiology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	ID4FO	WOS:000471632500001	31354295	Green Published, gold, Green Submitted			2022-04-25	
J	Zhang, XQ; Hu, XB; Mu, SJ; Zhan, YH; An, QX; Liu, ZX; Huang, XF				Zhang, Xianqing; Hu, Xingbin; Mu, Shijie; Zhan, Yonghua; An, Qunxing; Liu, Zhixin; Huang, Xiaofeng			RETRACTED: Apogossypolone inhibits the proliferation of LNCaP cells in vitro and in vivo (Retracted article. See vol. 17, pg. 6927, 2018)	MOLECULAR MEDICINE REPORTS			English	Article; Retracted Publication						apogossypolone; autophagy; apoptosis; LNCaP cell; nude mouse	SUPPRESSES TUMOR-GROWTH; BCL-2 FAMILY PROTEINS; HUMAN-PROSTATE-CANCER; HEPATOCELLULAR-CARCINOMA; COLON-CARCINOMA; APOPTOSIS; AUTOPHAGY; (-)-GOSSYPOL; GOSSYPOL; RADIATION	The aim of the present study was to investigate the anti-tumor effect of apogossypolone (ApoG2) on human LNCaP cells in vitro and in vivo. Cell viability was evaluated using an MTT assay. Cell autophagy and apoptosis-were detected by flow cytometry and using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay, respectively. Morphological autophagy alterations were observed by transmission electron microscopy. The formation of acidic vesicular organelles was assessed by acridine orange staining and fluorescence microscopy. Quantitative polymerase chain reaction (qPCR) was conducted to detect the expression levels of apoptosis-associated protein B-cell lymphoma 2 (Bcl-2) and Bak. The models of transplantation tumors in nude mice were established via subcutaneous injection of LNCaP cells. Growth of LNCaP cells was inhibited by ApoG2 treatment. Flow cytometry demonstrated that ApoG2 induced apoptosis in LNCaP cells. The Bcl-2 expression was decreased while Bak expression was increased. In addition, activation of cysteine aspartate protease (caspase)-3 and -8 was observed and 3-methyladenine (3-MA) enhanced apoptosis of LNCaP cells. Furthermore, nude mice treated with ApoG2 demonstrated a significant decrease in tumor volume and a significant increase in cell viability. Immunohistochemical analysis of tumor tissues demonstrated that ApoG2 enhanced caspase-3, -8, LC-3B and beclin-1 expression and reduced the expression of Bcl-2. ApoG2 was able to effectively suppress the growth of LNCaP cells through the induction of autophagy and apoptosis.	[Zhang, Xianqing; Hu, Xingbin; Mu, Shijie; An, Qunxing; Liu, Zhixin] Fourth Mil Med Univ, Xijing Hosp, Dept Blood Transfus, Xian 710032, Shaanxi, Peoples R China; [Zhan, Yonghua] Xidian Univ, Sch Life Sci & Technol, Engn Res Ctr Mol & Neuroimaging, Xian 710071, Shaanxi, Peoples R China; [Huang, Xiaofeng] Fourth Mil Med Univ, Sch Basic Med, Cent Lab, Xian 710032, Shaanxi, Peoples R China		Huang, XF (corresponding author), Fourth Mil Med Univ, Sch Basic Med, Cent Lab, 17 West Changle Rd, Xian 710032, Shaanxi, Peoples R China.	xiaofenghuang2012@126.com			National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81101100]; Natural Science Basic Research Plan in Shanxi Province of China [2012JQ4015]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [K50510100002, K50510100004]	This study was supported by the National Nature Science Foundation of China (no. 81101100), the Natural Science Basic Research Plan in Shanxi Province of China under Grant (no. 2012JQ4015) and the Fundamental Research Funds for the Central Universities (nos. K50510100002 and K50510100004).	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Med. Rep.	SEP	2014	10	3					1184	1194		10.3892/mmr.2014.2379			11	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	AN8LA	WOS:000340854500002	25060748	Green Published, hybrid, Green Submitted			2022-04-25	
J	Yan, SC; Tang, D; Hong, ZY; Wang, J; Yao, H; Lu, L; Yi, HM; Fu, SJ; Zheng, CJ; He, GC; Zou, H; Hou, XY; He, Q; Xiong, L; Li, QL; Deng, XY				Yan, Shichao; Tang, Da; Hong, Zhangyong; Wang, Jing; Yao, Hui; Lu, Lu; Yi, Huimei; Fu, Shujun; Zheng, Chanjuan; He, Guangchun; Zou, Heng; Hou, Xuyang; He, Qing; Xiong, Li; Li, Qinglong; Deng, Xiyun			CD133 peptide-conjugated pyropheophorbide-a as a novel photosensitizer for targeted photodynamic therapy in colorectal cancer stem cells	BIOMATERIALS SCIENCE			English	Article							IN-VIVO; PROGNOSTIC MARKER; TUMOR; PHTHALOCYANINES; IDENTIFICATION; NANOPARTICLES; CHALLENGES; PRINCIPLES; RESISTANCE; SURVIVAL	Colorectal cancer (CRC) is the third most common cancer around the world. Recent findings suggest that cancer stem cells (CSCs) play a pivotal role in the resistance to current therapeutic modalities, including surgery and chemotherapy. Photodynamic therapy (PDT) is a promising non-invasive therapeutic strategy for advanced metastatic CRC. Traditional photosensitizers such as pyropheophorbide-a (Pyro) lack tumor selectivity, causing unwanted treatment-related toxicity to the surrounding normal tissue. In order to enhance the targeting properties of Pyro, we synthesize a novel photosensitizer, CD133-Pyro, via the conjugation of Pyro to a peptide domain targeting CD133, which is highly expressed on CRC CSCs and correlated with poor prognosis of CRC patients. We demonstrate that CD133 Pyro possesses the targeted delivery capacity both in CRC CSCs derived from HT29 and SW620 cell lines and in a xenograft mouse model of tumor growth. CD133 Pyro PDT can promote the production of reactive oxygen species (ROS), suppress the sternness properties, and induce autophagic cell death in CRC CSCs. Furthermore, CD133-Pyro PDT has a potent inhibitory effect on CRC CSC-derived xenograft tumors in nude mice. These findings may offer a useful and important strategy for the treatment of CRC through targeting CSCs.	[Yan, Shichao; Zou, Heng; Hou, Xuyang; He, Qing; Xiong, Li; Li, Qinglong] Cent South Univ, Xiangya Hosp 2, Dept Gen Surg, Changsha 410011, Hunan, Peoples R China; [Yan, Shichao; Yao, Hui; Lu, Lu; Yi, Huimei; Fu, Shujun; Zheng, Chanjuan; He, Guangchun; Deng, Xiyun] Hunan Normal Univ, Key Lab Translat Canc Stem Cell Res, Changsha 410013, Hunan, Peoples R China; [Yan, Shichao; Yao, Hui; Lu, Lu; Yi, Huimei; Fu, Shujun; Zheng, Chanjuan; He, Guangchun; Deng, Xiyun] Hunan Normal Univ, Dept Pathol, Sch Med, Changsha 410013, Hunan, Peoples R China; [Yan, Shichao; Yao, Hui; Lu, Lu; Yi, Huimei; Fu, Shujun; Zheng, Chanjuan; He, Guangchun; Deng, Xiyun] Hunan Normal Univ, Dept Pathophysiol, Sch Med, Changsha 410013, Hunan, Peoples R China; [Tang, Da] Cent South Univ, Xiangya Hosp 3, Dept Gen Surg, Changsha 410013, Hunan, Peoples R China; [Hong, Zhangyong; Wang, Jing] Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R China; [Xiong, Li] Cent South Univ, Mol Imaging Res Ctr, Changsha 410013, Hunan, Peoples R China		Xiong, L; Li, QL (corresponding author), Cent South Univ, Xiangya Hosp 2, Dept Gen Surg, Changsha 410011, Hunan, Peoples R China.; Deng, XY (corresponding author), Hunan Normal Univ, Key Lab Translat Canc Stem Cell Res, Changsha 410013, Hunan, Peoples R China.; Deng, XY (corresponding author), Hunan Normal Univ, Dept Pathol, Sch Med, Changsha 410013, Hunan, Peoples R China.; Deng, XY (corresponding author), Hunan Normal Univ, Dept Pathophysiol, Sch Med, Changsha 410013, Hunan, Peoples R China.; Xiong, L (corresponding author), Cent South Univ, Mol Imaging Res Ctr, Changsha 410013, Hunan, Peoples R China.	lixionghn@csu.edu.cn; liqinglonga@sina.com; dengxiyunmed@hunnu.edu.cn		Deng, Xiyun/0000-0003-2203-970X	Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81773293, 81872167, 81472496, 31660266, 81873640, 81970569]; Key Project of Science and Technology Program of Hunan Provincial Science and Technology Department [2015GK3117, 2017WK2063]; Natural Science Foundation of Hunan ProvinceNatural Science Foundation of Hunan Province [2019JJ50874, 2020JJ4790]; Science and Technology Program of Changsha [kq1907079]	Xiangya Biomedical Electron Microscopy Core Facility of Central South University provided professional service with transmission electron microscopy. We thank H. Nikki March, PhD, from Edanz Group for editing a draft of this manuscript. This work was supported by the Natural Science Foundation of China (81773293, 81872167, 81472496, 31660266, 81873640, 81970569), the Key Project of Science and Technology Program of Hunan Provincial Science and Technology Department (2015GK3117, 2017WK2063), the Natural Science Foundation of Hunan Province (2019JJ50874, 2020JJ4790), and the Science and Technology Program of Changsha (kq1907079).	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Sci.	MAR 21	2021	9	6					2020	2031		10.1039/d0bm01874k			12	Materials Science, Biomaterials	Science Citation Index Expanded (SCI-EXPANDED)	Materials Science	RB5FB	WOS:000632135400033	33439161				2022-04-25	
