title: EGCG synergizes the therapeutic effect of cisplatin and oxaliplatin through autophagic pathway in human colorectal cancer cells.
abstract: Application of the platinum-based chemotherapy for colorectal cancer is restricted due to its severe cytotoxic effects. In this study we used synergistic strategies by combining (-)-Epigallocatechin gallate (EGCG) with cisplatin or oxaliplatin to minimize the ill effects of platinum-based therapy. MTS assay was used to examine the effect of EGCG, cisplatin and oxaliplatin on the proliferation of human colorectal cancer DLD-1 and HT-29 cells. Autophagic process was evaluated by detection of LC3-II protein, autophagosome formation, and quantification of Acidic Vesicular. Treatment of DLD-1 and HT-29 cells with EGCG plus cisplatin or oxaliplatin showed a synergistic effect on inhibition of cell proliferation and induction of cell death. EGCG enhanced the effect of cisplatin and oxaliplatin-induced autophagy in DLD-1 and HT-29 cells, as characterized by the accumulation of LC3-II protein, the increase of acidic vesicular organelles (AVOs), and the formation of autophagosome. In addition, transfection of DLD-1 and HT-29 cells with siRNA against ATG genes reduced EGCG synergistic effect. Our findings suggest that combining EGCG with cisplatin or oxaliplatin could potentiate the cytotoxicity of cisplatin and oxaliplatin in colorectal cancer cells through autophagy related pathway.
authors.affiliation: Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan 430071, China. Electronic address: hu.fen1989@163.com.
authors.forename: Fen
authors.initials: F
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Virology, National Laboratory of Antiviral and Tumor of Traditional Chinese Medicine, Institute of Medical Virology, Research Center of Food and Drug Evaluation, School of Medicine, Wuhan University, Wuhan 430071, China. Electronic address: fei.wei@qut.edu.au.
authors.forename: Fei
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan 430071, China. Electronic address: whu_yuleiwang@qq.com.
authors.forename: Yulei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan 430071, China. Electronic address: bibo2006@163.com.
authors.forename: Bibo
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan 430071, China. Electronic address: fy_whu@126.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan 430071, China. Electronic address: binxiong1961@whu.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Xiong
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D004357:Drug Synergism; D019073:HT29 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013662:Tea; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D009944:Organoplatinum Compounds; D013662:Tea; D000077150:Oxaliplatin; D002392:Catechin; C045651:epigallocatechin gallate; D002945:Cisplatin
keywords: Autophagic death; Cisplatin; EGCG; Oxaliplatin