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Cancers 2011, 3(3), 3353-3369; doi:10.3390/cancers3033353
Article

Prevention of Prostate Cancer with Oleanane Synthetic Triterpenoid CDDO-Me in the TRAMP Mouse Model of Prostate Cancer

1
, 1
, 1
, 2
, 3
, 1
 and 1,*
1 Department of General Surgery, Henry Ford Health System, Detroit, MI 48150, USA 2 Department of Diagnostic Radiology, Henry Ford Health System, Detroit, MI 48150, USA 3 Department of Public Health Sciences, Henry Ford Health System, Detroit, MI 48150, USA
* Author to whom correspondence should be addressed.
Received: 26 May 2011 / Revised: 12 August 2011 / Accepted: 15 August 2011 / Published: 19 August 2011
(This article belongs to the Special Issue Prostate Cancer)
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Abstract

2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), a synthetic analog of oleanolic acid, and its C28 methyl ester derivative (CDDO-Me), have shown potent antitumorigenic activity against a wide range of cancer cell lines, including prostate cancer cells in vitro, and inhibited the development of liver and lung cancer in vivo. In the present study, we examined the efficacy of CDDO-Me in preventing the development and progression of prostate cancer in the transgenic adenocarinoma of the mouse prostate (TRAMP) model. CDDO-Me inhibited the growth of murine TRAMPC-1 prostate cancer cells by inducing apoptosis through the inhibition of antiapoptotic p-Akt, p-mTOR and NF-κB. Early intervention with CDDO-Me (7.5 mg/kg) initiated at five weeks of age for 20 wk inhibited the progression of the preneoplastic lesions (low-grade PIN and high-grade-PIN) to adenocarcinoma in the dorsolateral prostate (DLP) and ventral prostate (VP) lobes of TRAMP mice. Even delayed administration of CDDO-Me started at 12 wk of age for 12 wk inhibited the development of adenocarcimona of the prostate. Both early and late treatment with CDDO-Me inhibited the metastasis of tumor to the distant organs. Treatment with CDDO-Me inhibited the expression of prosurvival p-Akt and NF-κB in the prostate and knocking-down Akt in TRAMPC-1 tumor cells sensitized them to CDDO-Me. These findings indicated that Akt is a target for apoptoxicity in TRAMPC-1 cells in vitro and potentially a target of CDDO-Me for inhibition of prostate cancer in vivo.
Keywords: prostate cancer; chemoprevention; CDDO-Me; apoptosis; Akt/mTOR/NF-kB signaling prostate cancer; chemoprevention; CDDO-Me; apoptosis; Akt/mTOR/NF-kB signaling
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Gao, X.; Deeb, D.; Liu, Y.; Arbab, A.S.; Divine, G.W.; Dulchavsky, S.A.; Gautam, S.C. Prevention of Prostate Cancer with Oleanane Synthetic Triterpenoid CDDO-Me in the TRAMP Mouse Model of Prostate Cancer. Cancers 2011, 3, 3353-3369.

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