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J Pharmacol Sci. 2015 May;128(1):27-34. doi: 10.1016/j.jphs.2015.04.003. Epub 2015 Apr 15.

EGCG synergizes the therapeutic effect of cisplatin and oxaliplatin through autophagic pathway in human colorectal cancer cells.

Author information

1
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.
2
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.
3
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.
4
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.
5
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.
6
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.

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.

KEYWORDS:

Autophagic death; Cisplatin; EGCG; Oxaliplatin

PMID:
26003085
DOI:
10.1016/j.jphs.2015.04.003
[Indexed for MEDLINE]
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