Anticancer effects of cepharanthine on human ovarian cancer cells

Cepharanthine (CEP) is a medicinal product derived from Stephania cepharantha Hayata, which possesses potent anticancer activities against several types of cancers such as leukemia, cholangiocarcinoma, non-small-cell lung cancer and hepatocarcinoma. However, its anticancer activity against ovarian cancer cells has never been reported. In this study, the anticancer effect of CEP and mechanisms underlying the anticancer effect of CEP were investigated in two human ovarian cancer cell lines, CaOV-3 (chemosensitive) and OVCAR-3 (chemoresistance), which has been reported to be resistant to clinically relevant concentrations of cisplatin and adriamycin. The present study demonstrated that CEP significantly inhibited the growth of CaOV-3 and OVCAR-3 cells in a concentration-dependent manner. Interestingly, CEP was more toxic to CaOV-3 cells (IC50 = 10.93±0.14 µM) than OVCAR-3 cells (IC50 = 31.20±1.27 µM). Additionally, CEP could induce cell cycle arrest at G1 phase in CaOV-3 cells but did not alter cell cycle distribution in OVCAR-3 cells. Mechanistic studies demonstrated that CEP markedly increased mRNA level of p21, a cyclin-dependent kinase inhibitor, in both ovarian cancer cell lines. CEP also decreased mRNA level of cyclin A in CaOV-3 as well as decreased the expression of cyclin A and E genes while increased cyclin D gene expression in OVCAR-3 cells. Moreover, CEP was found to trigger apoptosis, increase Bcl-xl mRNA and decrease Bax and Bak mRNA in CaOV-3 cells. Similarly, CEP induced cancer cells to undergo apoptosis and increased Bak mRNA level in OVCAR-3 cells. Therefore, the results from this study suggest that CEP could potentially be used as a novel anticancer drug for ovarian cancer treatment.