Improved chemosensitivity in cervical cancer to cisplatin: synergistic activity of mahanine through STAT3 inhibition

Cancer Lett. 2014 Aug 28;351(1):81-90. doi: 10.1016/j.canlet.2014.05.005. Epub 2014 May 14.

Abstract

Toxicity reduction of cisplatin is necessary for improved treatment of cancer. Here we have demonstrated the synergistic growth-inhibitory effect of cisplatin on cervical cancer cells in-combination with a nontoxic herbal carbazole alkaloid, mahanine. Mahanine enhanced cisplatin-induced apoptosis and reduced its effective concentration ∼5-8 folds. Mahanine inhibited JAK1 and Src and subsequently promoted proteasome-mediated degradation of STAT3. This event was further enhanced in-combination with cisplatin and subsequently inhibited cancer cell migration. Collectively, our results revealed that mahanine may be a prospective agent to reduce the concentration of cisplatin in adjunct for the treatment of cancer and thereby decreasing its toxicity.

Keywords: Cervical cancer; Cisplatin; Mahanine; STAT3; Synergism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Carbazoles / pharmacology*
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Female
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Membrane Potential, Mitochondrial / drug effects
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Proteolysis
  • STAT3 Transcription Factor / metabolism*
  • Uterine Cervical Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents
  • Carbazoles
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • mahanine
  • Cisplatin