Neferine Enhances the Antitumor Effect of Mitomycin-C in Hela Cells Through the Activation of p38-MAPK Pathway.

Current treatment options for patients with cervical cancer are far from desirable, with cervical cancer remaining to be one of the leading causes of cancer-related deaths; this highlights the need to formulate strategies that enhance the efficacy of available therapies. Mitomycin C (MMC) possesses antitumor effect in different cancers. However, the efficacy of MMC depends on other drugs in the combinational therapy and is often hampered by side-effects. Neferine, a natural alkaloid, exhibits antitumor effects in various cancers. In this study, we questioned the antitumor efficacy of a combinational treatment of neferine and MMC in cervical cancer cells. We found that neferine prominently enhanced the antitumor effects of MMC; this effect was dependent on the induction of apoptosis. Furthermore, we also provide a mechanistic insight and show that the enhanced apoptosis was a result of at least in part, a sustained activation of the p38 MAPK pathway in a ROS-dependent mechanism. Our results therefore demonstrate the potentiated antitumor effect of neferine and MMC on cervical cancer cells and may offer a potential treatment strategy for patients with cervical cancer. J. Cell. Biochem. 118: 3472-3479, 2017. © 2017 Wiley Periodicals, Inc.