The apoptotic mechanisms of MT-6, a mitotic arrest inducer, in human ovarian cancer cells

Sci Rep. 2017 Apr 7:7:46149. doi: 10.1038/srep46149.

Abstract

Patients with ovarian cancer are typically diagnosed at an advanced stage, resulting in poor prognosis since there are currently no effective early-detection screening tests for women at average-risk for ovarian cancer. Here, we investigated the effects of MT-6, a derivative of moscatilin, in ovarian cancer cells. Our investigation showed that MT-6 inhibited the proliferation and viability of ovarian cancer cells with submicromolar IC50 values. MT-6-treated SKOV3 cells showed significant cell cycle arrest at G2/M phase, followed by an increase in the proportion of cells in a sub-G1 phase. In addition, MT-6 induced a concentration-dependent increase in mitotic markers, mitotic kinases, cell cycle regulators of G2/M transition, and apoptosis-related markers in ovarian cancer cells. MT-6 treatment also induced mitochondrial membrane potential loss, JNK activation, and DR5 expression. Cotreatment of cells with the JNK inhibitor SP600125 considerably attenuated MT-6-induced apoptosis, mitochondria membrane potential loss, DR5 upregulation, and suppression of cell viability. MT-6 also inhibited tumor growth in an SKOV3 xenograft model without significant body weight loss. Together, our findings suggest that MT-6 is a potent anticancer agent with tumor-suppressive activity in vitro and in vivo that could be further investigated for ovarian cancer therapy in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Benzyl Compounds / pharmacology*
  • Biomarkers, Tumor / metabolism
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Enzyme Activation / drug effects
  • Female
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Mice, Nude
  • Mitosis / drug effects*
  • Ovarian Neoplasms / pathology*
  • Receptors, Death Domain / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Apoptosis Regulatory Proteins
  • Benzyl Compounds
  • Biomarkers, Tumor
  • Receptors, Death Domain
  • dendrophenol
  • JNK Mitogen-Activated Protein Kinases