High sensitivity of ovarian cancer cells to the synthetic triterpenoid CDDO-Imidazolide

Cancer Lett. 2009 Sep 18;282(2):214-28. doi: 10.1016/j.canlet.2009.03.018. Epub 2009 Apr 11.


In the present study we have explored the sensitivity of ovarian cancer cells to the synthetic triterpenoid CDDO-Imidazolide (CDDO-Im). For these studies we have used the A2780 ovarian cancer cell line and its chemoresistant derivatives A2780/ADR and A2780/CISP, OVCAR3, SKOV3 and HEY cancer cell lines and primary ovarian cancer cells, providing evidence that: (i) the majority of these cell lines are highly sensitive to the pro-apoptotic effects induced by CDDO-Im; (ii) TRAIL, added alone exerted only a weak proapoptotic, but clearly potentiated the cytotoxic effect elicited by CDDO-Im; (iii) the apoptotic effect induced by CDDO-Im involves GSH depletion, c-FLIP downmodulation and caspase-8 activation; (iv) CDDO-Im inhibits STAT3 activation and CDDO-Im sensitivity is inversely related to the level of constitutive STAT3 activation. Importantly, studies on primary ovarian cancer cells have shown that these cells are sensitive to the pro-apoptotic effects of CDDO-Im. These observations support the experimental use of synthetic triterpenoids in the treatment of ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology*
  • Apoptosis / drug effects
  • Caspase 8 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm
  • Enzyme Activation / drug effects
  • Female
  • Glutathione / metabolism
  • Humans
  • Imidazoles / pharmacology*
  • Mitochondria / drug effects
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / analysis
  • Receptors, Tumor Necrosis Factor / analysis
  • STAT3 Transcription Factor / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology
  • bcl-2-Associated X Protein / metabolism


  • 1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole
  • Antibiotics, Antineoplastic
  • BAX protein, human
  • Imidazoles
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human
  • bcl-2-Associated X Protein
  • Oleanolic Acid
  • Caspase 8
  • Glutathione