Apigenin enhances the cisplatin cytotoxic effect through p53-modulated apoptosis

Epidemiological and experimental evidence suggests that dietary flavonoids, including apigenin, have anticancer roles. Apigenin has been reported to elevate p53, a critical molecule in the induction of apoptosis. The present study aimed to investigate whether apigenin, a dietary flavonoid, improves the cytotoxic effect of cisplatin in a cancer cell culture system, and to elucidate the mechanism of this effect. Multiple tumor cell types were treated with apigenin, cisplatin or both drugs. Cell viability was evaluated, and the cytotoxic effect was determined biochemically and microscopically. Treatment with apigenin increased cisplatin-induced DNA damage and the apoptosis of tumor cells in a p53-dependent manner. Apigenin, when used with cisplatin, inhibited cell proliferation and promoted mitogen-activated protein kinase activation and subsequent p53 phosphorylation, leading to p53 accumulation and upregulation of proapoptotic proteins. Cisplatin is one of the most commonly used chemotherapeutic drugs for malignant tumors, but resistance to this drug occurs. The current results therefore demonstrate that dietary flavonoids may diminish the resistance of cancers to cisplatin.