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.
Division of Endocrinology, Department of Medicine, University of Fribourg, Fribourg, 1700, Switzerland.|Department of Biochemistry, Medical Research Institute, University of Alexandria, Alexandria, Egypt.
Wassim
0000-0002-9131-9687
W
Eid
Department of Biochemistry, Medical Research Institute, University of Alexandria, Alexandria, Egypt.
Wafaa
W
Abdel-Rehim
D000970:Antineoplastic Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000819:agonists / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016685:Mitomycin / Q000819:agonists / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D009363:Neoplasm Proteins; C057222:neferine; D016685:Mitomycin; D048051:p38 Mitogen-Activated Protein Kinases
CERVICAL CANCER; MITOMYCIN C; NEFERINE; ROS; p38 MAPK