Role of reactive oxygen species (ROS) in CDDO-Me-mediated growth inhibition and apoptosis in colorectal cancer cells

Xiaohua Gao, Dorrah Deeb, Patricia Liu, Yongbo Liu, Ali Syed Arbab, Scott A. Dulchavsky, Subhash C. Gautam

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

CDDO-Me, an oleanane synthetic triterpenoid has shown strong antitumorigeic activity towards diverse cancer cell types including colorectal cancer cells. In the present study, we investigated the role of free radicals in the growth inhibitory and apoptosis-inducing activity of CDDO-Me in colorectal cancer cells lines. Results demonstrated that CDDO-Me potently inhibited the growth of colorectal cancer cells and pretreatment of cancer cells with small-molecule antioxidant N-acetylcysteine (NAC) completely blocked the growth inhibitory activity of CDDO-Me. CDDO-Me caused the generation of reactive oxygen species, which was inhibited by NAC and mitochondrial chain 1 complex inhibitors DPI and rotenone. CDDO-Me induced apoptosis as demonstrated by the cleavage of PARP-1, activation of procaspases -3, -8, and -9 and mitochondrial depolarization and NAC blocked the activation of these apoptosis related processes. Furthermore, induction of apoptosis by CDDO-Me was associated with the inhibition of antiapoptotic/ prosurvival Akt, mTOR and NF-κB signaling proteins and the inhibition of these signaling molecules was blocked by NAC. Together these studies provided evidence that CDDO-Me is a potent anticancer agent, which imparts growth inhibition and apoptosis in colorectal cancer cells through the generation of free radicals.

Original languageEnglish (US)
Pages (from-to)119-127
Number of pages9
JournalJournal of Experimental Therapeutics and Oncology
Volume9
Issue number2
StatePublished - Jun 22 2011
Externally publishedYes

Fingerprint

Colorectal Neoplasms
Reactive Oxygen Species
Apoptosis
Acetylcysteine
Growth
Free Radicals
Rotenone
Caspase 8
methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate
Caspase 3
Antineoplastic Agents
Neoplasms
Antioxidants
Cell Line

Keywords

  • Apoptosis
  • CDDO-Me
  • Colorectal cancer
  • ROS
  • Signaling proteins

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Cancer Research

Cite this

Role of reactive oxygen species (ROS) in CDDO-Me-mediated growth inhibition and apoptosis in colorectal cancer cells. / Gao, Xiaohua; Deeb, Dorrah; Liu, Patricia; Liu, Yongbo; Arbab, Ali Syed; Dulchavsky, Scott A.; Gautam, Subhash C.

In: Journal of Experimental Therapeutics and Oncology, Vol. 9, No. 2, 22.06.2011, p. 119-127.

Research output: Contribution to journalArticle

Gao, Xiaohua ; Deeb, Dorrah ; Liu, Patricia ; Liu, Yongbo ; Arbab, Ali Syed ; Dulchavsky, Scott A. ; Gautam, Subhash C. / Role of reactive oxygen species (ROS) in CDDO-Me-mediated growth inhibition and apoptosis in colorectal cancer cells. In: Journal of Experimental Therapeutics and Oncology. 2011 ; Vol. 9, No. 2. pp. 119-127.
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