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 Syed Arbab, Subhash C. Gautam

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 1 2013
Externally publishedYes

Fingerprint

Ovarian Neoplasms
B-Cell Lymphoma
Reactive Oxygen Species
NF-kappa B
Inhibitor of Apoptosis Proteins
Caspase 8
Mitochondrial Membrane Potential
Annexin A5
Sirolimus
Fluorescein
Caspase 3
Down-Regulation
Cell Proliferation
methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate
oleanane
Apoptosis
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

ROS mediate proapoptotic and antisurvival activity of oleanane triterpenoid cddo-me in ovarian cancer cells. / Gao, Xiaohua; Liu, Yongbo; Deeb, Dorrah; Liu, Patricia; Liu, Annie; Arbab, Ali Syed; Gautam, Subhash C.

In: Anticancer Research, Vol. 33, No. 1, 01.01.2013, p. 215-222.

Research output: Contribution to journalArticle

Gao, X, Liu, Y, Deeb, D, Liu, P, Liu, A, Arbab, AS & Gautam, SC 2013, 'ROS mediate proapoptotic and antisurvival activity of oleanane triterpenoid cddo-me in ovarian cancer cells', Anticancer Research, vol. 33, no. 1, pp. 215-222.
Gao, Xiaohua ; Liu, Yongbo ; Deeb, Dorrah ; Liu, Patricia ; Liu, Annie ; Arbab, Ali Syed ; Gautam, Subhash C. / ROS mediate proapoptotic and antisurvival activity of oleanane triterpenoid cddo-me in ovarian cancer cells. In: Anticancer Research. 2013 ; Vol. 33, No. 1. pp. 215-222.
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