Synthetic triterpenoid CDDO prevents the progression and metastasis of prostate cancer in TRAMP mice by inhibiting survival signaling

Dorrah Deeb, Xiaohua Gao, Yongbo Liu, Daniel Jiang, George W. Divine, Ali Syed Arbab, Scott A. Dulchavsky, Subhash C. Gautam

Research output: Contribution to journalArticle

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Abstract

In an extension of our previous studies showing potent antitumorigenic activity of synthetic triterpenoids of oleanolic acid against prostate cancer cell lines, we examined the efficacy of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) in preventing the development and/or progression of prostate cancer in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Data show that oral gavage with CDDO (10 μmol/kg) for 20 weeks resulted in inhibition of the progression of preneoplastic lesions in the dorsolateral prostate and ventral prostate to adenocarcinoma without toxicity. CDDO also inhibited metastasis of tumor to the distant organs. Treatment with CDDO significantly inhibited cell proliferation, reduced the density of blood vessels and promoted apoptosis in the prostatic tissue. Further, Akt, NF-κB and NF-κB regulated Bcl-2, Bcl-xL, survivin and cIAP1 appear to be the molecular targets of CDDO for inhibiting the progression of prostate cancer in TRAMP mice. Thus, these studies show for the first time the potential of CDDO for chemoprevention of human prostate cancer.

Original languageEnglish (US)
Pages (from-to)757-764
Number of pages8
JournalCarcinogenesis
Volume32
Issue number5
DOIs
StatePublished - May 13 2011
Externally publishedYes

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Transgenic Mice
Prostate
Prostatic Neoplasms
Adenocarcinoma
Neoplasm Metastasis
Survival
Oleanolic Acid
Chemoprevention
Blood Vessels
Cell Proliferation
Apoptosis
Cell Line
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Cancer Research

Cite this

Synthetic triterpenoid CDDO prevents the progression and metastasis of prostate cancer in TRAMP mice by inhibiting survival signaling. / Deeb, Dorrah; Gao, Xiaohua; Liu, Yongbo; Jiang, Daniel; Divine, George W.; Arbab, Ali Syed; Dulchavsky, Scott A.; Gautam, Subhash C.

In: Carcinogenesis, Vol. 32, No. 5, 13.05.2011, p. 757-764.

Research output: Contribution to journalArticle

Deeb, Dorrah ; Gao, Xiaohua ; Liu, Yongbo ; Jiang, Daniel ; Divine, George W. ; Arbab, Ali Syed ; Dulchavsky, Scott A. ; Gautam, Subhash C. / Synthetic triterpenoid CDDO prevents the progression and metastasis of prostate cancer in TRAMP mice by inhibiting survival signaling. In: Carcinogenesis. 2011 ; Vol. 32, No. 5. pp. 757-764.
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