Inhibitory effect of black tea pigments, theaflavin-3/3′-gallate against cisplatin-resistant ovarian cancer cells by inducing apoptosis and G1 cell cycle arrest

Adverse side effects and acquired resistance to conventional chemotherapy based on platinum drive the exploration of other selective anticancer drugs. Theaflavin-3-gallate (TF2a) and theaflavin-3′-gallate (TF2b), theaflavin monomers in black tea, exhibited a potent growth inhibitory effect on cisplatin-resistant ovarian cancer A2780/CP70 cells and were less cytotoxic to normal ovarian IOSE-364 cell line. Flow cytometry analysis and western blotting indicated that TF2a and TF2b induced apoptosis and G1 cell cycle arrest in ovarian cancer A2780/CP70 cells. Hoechst 33342 staining was used to confirm the apoptotic effect. Downregulation of CDK2 and CDK4 for TF2a and CDK2 and cyclin E1 for TF2b led to the accumulation of cells in G1 phase. TF2a and TF2b induced apoptosis and G1 through p53-dependent pathways. TF2a and TF2b induced DNA damage through ATM/Chk/p53 pathway. TF2a and TF2b also induced inhibition of A2780/CP70 cells through Akt and MAPK pathways. The results of this study implied that TF2a and TF2b might help prevent and treat platinum-resistant ovarian cancer.