Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53

•Combination of chrysin and cisplatin promotes cell death in cancer cells.•Cell death promoted by cisplatin plus chrysin was caspase-dependent apoptosis.•Pretreatment of chrysin enhances the p53 accumulation through activating ERK1/2.•Promotion of Bax, DR5 expression and suppression of Bcl2 expression were observed.•Extrinsic and intrinsic apoptosis were found in the combinative effect.

Cisplatin is a chemotherapy drug commonly used for the treatment of human cancers, however, drug resistance poses a major challenge to clinical application of cisplatin in cancer therapy. Recent studies have shown that chrysin, a natural flavonoid widely found in various plants and foods, demonstrated effective anti-cancer activity. In the present study, we found that the combination chrysin and cisplatin significantly enhanced the apoptosis of Hep G2 cancer cells. Combination of chrysin and cisplatin increased the phosphorylation and accumulation of p53 through activating ERK1/2 in Hep G2 cells, which led to the overexpression of the pro-apoptotic proteins Bax and DR5 and the inhibition of the anti-apoptotic protein Bcl-2. In addition, combination of chrysin and cisplatin promoted both extrinsic apoptosis by activating caspase-8 and intrinsic apoptosis by increasing the release of cytochrome c and activating caspase-9 in Hep G2 cells. Our results suggest that combination of chrysin and cisplatin is a promising strategy for chemotherapy of human cancers that are resistant to cisplatin.