Synthetic triterpenoids inhibit growth, induce apoptosis and suppress pro-survival Akt, mTOR and NF-κB signaling proteins in colorectal cancer cells

Xiaohua Gao, Dorrah Deeb, Jiang Hao, Yongbo Liu, Ali S. Arbab, Scott A. Dulchavsky, Subhash C. Gautam

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Lack of apoptotic cell death has been implicated in malignant transformation and resistance to anticancer therapies. The promotion of apoptosis in cancer cells could potentially lead to the regression and improved prognosis of refractory colorectal cancer. Synthetic triterpenoids have shown strong antitumorigenic activity towards diverse cancer cell types, but have not been investigated for colorectal cancer. In the present study, we tested the apoptosis-inducing activity of oleanane triterpenoid 2-cyano-3,12-dioxooleana-1, 9(11)-dien-28-oic acid (CDDO) and its C-28 methyl ester (CDDO-Me) and C-28 imidazole (CDDO-Im) derivatives in colorectal cancer cells lines. Cell growth/viability assay (MTS) demonstrated that colorectal cancer cells are highly sensitive to CDDO-Me at concentrations of 1.25 to 10 μM. The primary mode of tumor cell destruction was apoptosis as demonstrated by the cleavage of PARP-1, activation of procaspases -3, -8, and -9 and mitochondrial depolarization. Induction of apoptosis by CDDO-Me was associated with the inhibition of pro-survival Akt, NF-κB and mTOR signaling proteins and NF-κB-regulated anti-apoptotic Bcl-2, Bcl-xL, Bad and survivin. These studies provide rationale for clinical evaluation of CDDO-Me for the treatment of advanced chemotherapy refractory colorectal cancer.

Original languageEnglish (US)
Pages (from-to)785-792
Number of pages8
JournalAnticancer research
Volume30
Issue number3
StatePublished - Mar 1 2010
Externally publishedYes

Keywords

  • Apoptosis
  • Colorectal cancer
  • Signaling proteins
  • Synthetic triterpenoids

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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