ROS mediate proapoptotic and antisurvival activity of oleanane triterpenoid cddo-me in ovarian cancer cells

Xiaohua Gao, Yongbo Liu, Dorrah Deeb, Patricia Liu, Annie Liu, Ali S. Arbab, Subhash C. Gautam

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Oleanane triterpenoids are broad-spectrum antiproliferative and proapoptotic agents. In this study, we investigated whether reactive oxygen species (ROS) play a role in the antitumor activity of methyl-2-cyano-3, 12-dioxooleana- 1, 9(11)-dien-28-oate (CDDO-Me) in OVCAR-5 and MDAH 2774 ovarian cancer cells. Treatment with CDDO-Me caused the generation of ROS (H2O2) and pre-treatment with Nacetylcysteine (NAC) prevented the generation of ROS. NAC also blocked the inhibition of cell proliferation by CDDO-Me. Likewise, NAC prevented the CDDO-Me-caused binding of fluorescein isothiocyanate (FITC)-tagged annexin V, cleavage of poly ADP-ribose polymerase-1 (PARP-1), procaspases-3, -8 and -9 and loss of mitochondrial membrane potential. CDDO-Me inhibited the expression of prosurvival phospho- AKT (p-AKT), phospho-mammalian target of rapamycin (p-mTOR) and nuclear factor-kappa B (NF-κB) (p65) signaling molecules and NF-κB-regulated antiapoptotic B-cell lymphoma-2 (BCL-2), B-cell lymphoma-extra large (BCL-xL), cellular inhibitor of apoptosis protein 1(c-IAP1) and survivin, but pre-treatment with NAC blocked the down-modulation of these signaling and antiapoptotic proteins by CDDO-Me. Together, these results indicate the pivotal role ROS play in the antiproliferative- and apoptosis-inducing activity of CDDO-Me in ovarian cancer cells; however, the role of ROS in the down-regulation of prosurvival AKT, mTOR, NF-κB and antiapoptotic BCL-2, BCL-xL, c-IAP1 and survivin warrants further investigation.

Original languageEnglish (US)
Pages (from-to)215-222
Number of pages8
JournalAnticancer research
Volume33
Issue number1
StatePublished - Jan 2013
Externally publishedYes

Keywords

  • AKT
  • Apoptosis
  • CDDO-Me
  • MTOR
  • NF-κB
  • Ovarian cancer
  • ROS

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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