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

ABSTRACT 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. In its war on cancer, the human race have achieved significant milestones, however, cancer still claims many lives each year. Here, we show that neferine enhance the antitumor effect of mitomycin‐C. Our findings could provide a potential treatment strategy for cervical cancer patients.