Synergistic effect of black tea polyphenol, theaflavin-3,3'-digallate with cisplatin against cisplatin resistant human ovarian cancer cells.

Theaflavin-3, 3'-digallate (TF3) is a phenolic compound extracted from black tea. We previously demonstrated that TF3 selectively inhibited ovarian cancer cells. Ovarian cancer has high death rate because of acquired cisplatin resistance. We aimed to investigate the synergistic effect of TF3 and cisplatin (CDDP) against cisplatin resistant ovarian cancer cells. In the present study, combination treatment with TF3 and CDDP showed a synergistic cytotoxic effect in A2780/CP70 and OVCAR3 cells. Combination treatment showed a synergistic pro-apoptotic effect and synergistically induced G1/S phase cell cycle arrest. Synergistic apoptosis was accompanied by regulating protein expression of cleaved caspase 3/7, cytochrome c, Bax and Bcl-2. Combination treatment induced G1/S phase cell cycle arrest via regulating protein expression of cyclin A2, cyclin D1, cyclin E1 and CDK2/4. Combination treatment could synergistically down-regulate Akt phosphorylation in both cell lines. TF3 may be used as an adjuvant for the treatment of advanced ovarian cancer.