The green tea catechin epigallocatechin gallate induces cell cycle arrest and shows potential synergism with cisplatin in biliary tract cancer cells

BMC Complementary and Alternative Medicine

Research Article

Martin Pichler¹  Andrej Wagner²  Christian Mayr³  Tobias Kiesslich³  Daniel Neureiter⁴  Romana Illig⁴  Martin Jakab⁵  Frieder Berr⁶ 

[1] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;Department of Internal Medicine I, Salzburger Landeskliniken – SALK, Paracelsus Medical University, Salzburg, Austria;Department of Internal Medicine I, Salzburger Landeskliniken – SALK, Paracelsus Medical University, Salzburg, Austria;Laboratory for Tumour Biology and Experimental Therapies, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria;Institute of Pathology, Salzburger Landeskliniken – SALK, Paracelsus Medical University, Salzburg, Austria;Laboratory for Functional and Molecular Membrane Physiology, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria;Laboratory for Tumour Biology and Experimental Therapies, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria;

关键词: EGCG;    Green tea;    Biliary tract cancer;    Drug synergism;    Cisplatin;    Cell cycle arrest;   

DOI  :  10.1186/s12906-015-0721-5

 received in 2015-04-03, accepted in 2015-06-12,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe green tea catechin epigallocatechin gallate (EGCG) was shown to effectively inhibit tumor growth in various types of cancer including biliary tract cancer (BTC). For most BTC patients only palliative therapy is possible, leading to a median survival of about one year. Chemoresistance is a major problem that contributes to the high mortality rates of BTC. The aim of this study was to investigate the cytotoxic effect of EGCG alone or in combination with cisplatin on eight BTC cell lines and to investigate the cellular anti-cancer mechanisms of EGCG.MethodsThe effect of EGCG treatment alone or in combination with the standard chemotherapeutic cisplatin on cell viability was analyzed in eight BTC cell lines. Additionally, we analyzed the effects of EGCG on caspase activity, cell cycle distribution and gene expression in the BTC cell line TFK-1.ResultsEGCG significantly reduced cell viability in all eight BTC cell lines (p < 0.05 or p < 0.01, respectively, for most cell lines and EGCG concentrations > 5 μM). Combined EGCG and cisplatin treatment showed a synergistic cytotoxic effect in five cell lines and an antagonistic effect in two cell lines. Furthermore, EGCG reduced the mRNA levels of various cell cycle-related genes, while increasing the expression of the cell cycle inhibitor p21 and the apoptosis-related death receptor 5 (p < 0.05). This observation was accompanied by an increase in caspase activity and cells in the sub-G1 phase of the cell cycle, indicating induction of apoptosis. EGCG also induced a down-regulation of expression of stem cell-related genes and genes that are associated with an aggressive clinical character of the tumor, such as cd133 and abcg2.ConclusionsEGCG shows various anti-cancer effects in BTC cell lines and might therefore be a potential anticancer drug for future studies in BTC. Additionally, EGCG displays a synergistic cytotoxic effect with cisplatin in most tested BTC cell lines.Graphical abstractSummary illustration

【 授权许可】

Unknown   
© Mayr et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.