Green tea catechin epigallocatechin gallate causes apoptosis and shows potential synergism with cisplatin in biliary tract cancer cells

C Mayr; A Wagner; D Neureiter; M Pichler; M Ritter; R Illig; F Berr; T Kiesslich

doi:10.1055/s-0035-1551754

Zeitschrift für Gastroenterologie, Inhaltsverzeichnis

Green tea catechin epigallocatechin gallate causes apoptosis and shows potential synergism with cisplatin in biliary tract cancer cells

C Mayr ¹, A Wagner ², D Neureiter ³, M Pichler ⁴, M Ritter ⁵, R Illig ³, F Berr ², T Kiesslich ¹

¹Salzburger Landeskliniken/Paracelsus Medical University, Department of Internal Medicine I/Laboratory for Tumour Biology and Experimental Therapies, Institute of Physiology and Pathophysiology, Salzburg, Austria
²Salzburger Landeskliniken/Paracelsus Medical University, Department of Internal Medicine I, Salzburg, Austria
³Paracelsus Medical University, Institute of Pathology, Salzburg, Austria
⁴Medical University of Graz (MUG), Division of Oncology, Department of Internal Medicine, Graz, Austria
⁵Paracelsus Medical University, Institute of Physiology and Pathophysiology, Salzburg, Austria

Abstract

Question:

Chemoresistance is a major problem that contributes to the high mortality rates of biliary tract cancer (BTC). It is known that the green tea catechin epigallocatechin gallate (EGCG) has anti-cancer effects alone or in combination with standard chemotherapeutics in various types of cancer, including BTC. In this study we investigated the cytotoxic effects of EGCG in BTC cells. We further investigated potential synergistic effects of EGCG and cisplatin chemotherapy.

Methods:

Cytotoxic effects of the drugs were evaluated in eight BTC cell lines using resazurin cell viability and caspase activity assays as well as cell cycle analysis using propidium iodide staining (FACS). Changes in gene expression after EGCG treatment were measured with quantitative real time reverse transcription PCR.

Results:

EGCG caused a significant reduction of cell viability in all eight BTC cell lines. When combined with cisplatin, we observed a synergistic cytotoxic effect in five cell lines. Treatment with EGCG reduced mRNA levels of various cell cycle-promoting genes, while increasing the expression of the cell cycle inhibitor p21 and the apoptosis-related death receptor-5 (dr5). EGCG increased caspase activity and the cell fraction in the sub-G1 phase of the cell cycle indicating that EGCG causes cell cycle arrest and apoptosis. Additionally, EGCG decreased mRNA levels of genes that are associated with cancer stem cells and aggressive clinical characteristics of the tumor.

Conclusions:

The green tea catechin EGCG shows clear anti-cancer effects in BTC cells and might therefore be an interesting (adjuvant) substance for future studies.