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

J Cell Biochem. 2017 Oct;118(10):3472-3479. doi: 10.1002/jcb.26006. Epub 2017 May 15.

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.

Keywords: CERVICAL CANCER; MITOMYCIN C; NEFERINE; ROS; p38 MAPK.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Benzylisoquinolines / agonists
  • Benzylisoquinolines / pharmacology*
  • Female
  • HeLa Cells
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Mitomycin / agonists
  • Mitomycin / pharmacology*
  • Neoplasm Proteins / metabolism*
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / enzymology*
  • Uterine Cervical Neoplasms / pathology
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Benzylisoquinolines
  • Neoplasm Proteins
  • neferine
  • Mitomycin
  • p38 Mitogen-Activated Protein Kinases