Synthetic oleanane triterpenoid, CDDO-Me, induces apoptosis in ovarian cancer cells by inhibiting prosurvival AKT/NF-κB/mTOR signaling

Xiaohua Gao, Yongbo Liu, Dorrah Deeb, Ali S. Arbab, Austin M. Guo, Scott A. Dulchavsky, Subhash C. Gautam

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Synthetic oleanane triterpenoids are novel agents which have shown strong antitumorigenic activity against a wide range of cancer types in vitro. The objective of the present study was to determine the anticancer activity of methyl-2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-oate (CDDO-Me) derived from CDDO, a synthetic analog of oleanolic acid, and its mechanism of action in killing of human ovarian cancer cells. CDDO-Me strongly inhibited the growth of ovarian cancer cells by inducing apoptosis characterized by increased annexin V binding, cleavage of poly (ADP-ribose) polymerase (PARP-1) and procaspases-3, -8 and -9. In addition, CDDO-Me induced mitochondrial depolarization. Western blot analysis showed inhibition of prosurvival (antiapoptotic) phospho-AKT (p-AKT), nuclear factor kappa B (NF-κB) (p65) and phospho- mammalian target of rapamycin (p-mTOR) signaling proteins in cells treated with CDDO-Me. Abrogation of AKT which regulates both NF-κB and mTOR increased the sensitivity of tumor cells to CDDO-Me. Thus, these data showing strong growth-inhibitory and apoptosis-inducing activity of CDDO-Me for ovarian cancer cells through the inhibition of AKTI NF-κB/mTOR signaling pathway provide basis for evaluation of CDDO-Me for ovarian cancer.

Original languageEnglish (US)
Pages (from-to)3673-3681
Number of pages9
JournalAnticancer research
Volume31
Issue number11
StatePublished - Nov 1 2011
Externally publishedYes

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Keywords

  • 12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me)
  • AKT
  • Apoptosis
  • Methyl-2-cyano-3
  • NF-κB
  • Ovarian cancer
  • mTOR

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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