Synergistic effects of green tea extract and paclitaxel in the induction of mitochondrial apoptosis in ovarian cancer cell lines

Green tea is a natural compound with anti-neoplastic properties. Paclitaxel (PTX) is a natural anti-tumor medication used to manage patients with advanced ovarian cancer. This manuscript evaluated the cytotoxic effects of green tea extract combined with PTX drug in two human ovarian cancer cell lines (p53-negative cell line, SKOV-3; and mutant type p53 cell line, OVCAR-3) and underlying mechanisms. The human ovarian cancer cell lines were treated with green tea extract, PTX, and green tea plus PTX for 24 h, and cell viability was assessed using the MTT method. Flow cytometric analyses were carried out to detect apoptosis. For the apoptotic process, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were applied to study pAkt, Bax, Bcl-2, Cytochrome C (Cyt-C), cleaved-caspase-3, and cleaved-caspase-9 levels after drug treatments. Our results pointed out that various green tea (25 and 50 µg/ml) concentrations combined with PTX (20 and 40 µg/ml) synergistically inhibited cell viability of cancer cells more than green tea or PTX alone after 24 h of treatment. Also, green tea and PTX combination induced apoptosis in ovarian cancer cells by blocking the phosphorylation of Akt and the expression of Bcl-2 while inducing Bax, Cyt-C, cleaved-caspase 3, and cleaved-caspase 9. Our results showed that the combination of green tea and PTX could be more potent than the individual drug to induce cytotoxicity and apoptosis in ovarian cancer cells.