Inhibitory effect of epigallocatechin-3-gallate on growth and invasion in human biliary tract carcinoma cells.

Takada M, Ku Y, Habara K, Ajiki T, Suzuki Y, Kuroda Y.

First Department of Surgery, Kobe University School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

Based on recent evidence that tea consumption contributes to a decreased incidence of human carcinomas, a number of investigators have focused on the mechanisms of cancer prevention by tea extracts, especially green tea polyphenols. Epigallocatechin-3-gallate (EGCG) is a representative polyphenol that inhibits the activity of the cyclin-dependent kinases of cdk2 and cdk4. This suggests that EGCG may exert its growth-inhibitory effects through modulation of G1 regulatory proteins such as cdk2 and cdk4. The human biliary tract carcinoma cells (TGBC-2, SK-ChA-1, and NOZC-1) were treated with different doses of EGCG (0, 25, 50, 100, and 200 mM) for 48 hours in cell medium. Cell proliferation was analyzed by WST-1 colorimetric assay. For the cell-invasion analysis, the cells were incubated with 100 mM of EGCG for 2 hours. The cells were then added into a Matrigel-coated Cell Insert. After incubation at 37 degrees C for 24 hours, the cells visible through the Matrigel were counted under the microscope. All human biliary tract cancer cells studied showed a significant suppression of cell growth by EGCG treatment in a dose-dependent manner (27.2%, 16.0%, and 10.1%, in TGBC-2, SK-ChA-1, and NOZC-1, respectively, at the dose of 200 mM). Epigallocatechin-3-gallate treatment also produced a significant suppression of invasive ability of the carcinoma cells (12.6%, 11.2%, 7.9%, in TGBC-2, SK-ChA-1, and NOZC-1, respectively, at a dose of 100 mM). These data indicated that EGCG might be a potent biological inhibitor of human biliary tract cancers, reducing their proliferative and invasive activities.