Inhibition of epithelial ovarian cancer by Minnelide, a water-soluble pro-drug

Gynecol Oncol. 2014 Nov;135(2):318-24. doi: 10.1016/j.ygyno.2014.08.031. Epub 2014 Aug 27.

Abstract

Objective: Minnelide is a water-soluble pro-drug of triptolide, a natural product. The goal of this study was to evaluate the effectiveness of Minnelide on ovarian cancer growth in vitro and in vivo.

Methods: The effect of Minnelide on ovarian cancer cell proliferation was determined by real time electrical impedance measurements. Multiple mouse models with C200 and A2780 epithelial ovarian cancer cell lines were used to assess the efficacy of Minnelide in inhibiting ovarian cancer growth.

Results: Minnelide decreased cell viability of both platinum sensitive and resistant epithelial ovarian cancer cells in vitro. Minnelide with carboplatin showed additive effects in vitro. Minnelide monotherapy increased the survival of mice bearing established ovarian tumors. Minnelide, in combination with carboplatin and paclitaxel, improved overall survival of mice.

Conclusions: Minnelide is a promising pro-drug for the treatment of ovarian cancer, especially when combined with standard chemotherapy.

Keywords: Chemotherapy; Minnelide; Ovarian cancer; Triptolide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects*
  • Carboplatin / administration & dosage
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Diterpenes / pharmacology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Screening Assays, Antitumor
  • Electric Impedance
  • Epoxy Compounds / pharmacology
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / pathology
  • Organophosphates / pharmacology*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / administration & dosage
  • Phenanthrenes / pharmacology*
  • Prodrugs / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Diterpenes
  • Epoxy Compounds
  • Organophosphates
  • Phenanthrenes
  • Prodrugs
  • triptolide
  • 14-O-phosphonooxymethyltriptolide disodium salt
  • Carboplatin
  • Paclitaxel