Abstract
BACKGROUND: Green tea polyphenols are chemopreventive in several cancer models but their use as adjunctive therapeutic agents for cancer is unknown. AIMS: Cholangiocarcinomas respond poorly to chemotherapeutic agents and our aims were to assess the utility of green tea polyphenols as adjuncts to chemotherapy for cholangiocarcinoma. MATERIALS AND METHODS: We assessed the effect of purified green tea catechins on chemotherapy-induced apoptosis in KMCH, CC-LP-1 and Mz-ChA-1 human cholangiocarcinoma cells, and on chemosensitivity of Mz-ChA-1 cell xenografts in nude mice. RESULTS: Epigallocatechin-gallate (EGCG), but not the structurally related catechin epigallocatechin, sensitized cells to apoptosis induced by gemcitabine (GEM), mitomycin C or 5-fluorouracil in vitro. Mitochondrial membrane depolarization, cytosolic cytochrome c expression and apoptosis were increased in cells incubated with EGCG and GEM compared with either agent alone. Furthermore, EGCG decreased in vivo growth and increased the sensitivity to GEM of Mz-ChA-1 cell xenografts in nude mice. CONCLUSIONS: The green tea polyphenol EGCG sensitizes human cholangiocarcinoma cells to chemotherapy-induced apoptosis and warrants evaluation as an adjunct to chemotherapy for the treatment of human cholangiocarcinoma.