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Telomerase Reverse Transcriptase (TERT) is a Therapeutic Target of Oleanane Triterpenoid CDDO-Me in Prostate Cancer
Department of General Surgery, Henry Ford Health System, Detroit, MI 48202, USA
Department of Radiology, Henry Ford Health System, Detroit, MI 48202, USA
* Author to whom correspondence should be addressed.
Received: 9 November 2012; in revised form: 20 November 2012 / Accepted: 6 December 2012 / Published: 11 December 2012
Abstract: Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is an synthetic oleanane triterpenoid with strong antiprolifertive and proapoptotic activities in cancer cells. However, the effect of CDDO-Me on human telomerase reverse transcriptase (hTERT) and its telomerase activity in prostate cancer cells has not been studied. We investigated the role of hTERT in mediating the anticancer activity of CDDO-Me in prostate cancer cells in vitro and in vivo. The inhibition of cell proliferation and induction of apoptosis by CDDO-Me in LNCaP and PC-3 prostate cancer cell lines was associated with the inhibition of hTERT gene expression, hTERT telomerase activity and a number of proteins that regulate hTERT transcriptionally and post-translationally. Furthermore, ablation of hTERT protein increased the sensitivity of cancer cells to CDDO-Me, whereas its overexpression rendered them resistant to CDDO-Me. In addition, inhibition of progression of preneoplastic lesions (i.e., low and high-grade prostate intraepithelial neoplasms, PINs) to adenocarcinoma of the prostate by CDDO-Me in TRAMP mice was associated with significant decrease in TERT and its regulatory proteins in the prostate gland. These data provide evidence that telomerase is a potential target of CDDO-Me for the prevention and treatment of prostate cancer.
Keywords: CDDO-Me; hTERT; telomerase activity; apoptosis; prostate cancer
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Liu, Y.; Gao, X.; Deeb, D.; Arbab, A.S.; Gautam, S.C. Telomerase Reverse Transcriptase (TERT) is a Therapeutic Target of Oleanane Triterpenoid CDDO-Me in Prostate Cancer. Molecules 2012, 17, 14795-14809.
Liu Y, Gao X, Deeb D, Arbab AS, Gautam SC. Telomerase Reverse Transcriptase (TERT) is a Therapeutic Target of Oleanane Triterpenoid CDDO-Me in Prostate Cancer. Molecules. 2012; 17(12):14795-14809.
Liu, Yongbo; Gao, Xiaohua; Deeb, Dorrah; Arbab, Ali S.; Gautam, Subhash C. 2012. "Telomerase Reverse Transcriptase (TERT) is a Therapeutic Target of Oleanane Triterpenoid CDDO-Me in Prostate Cancer." Molecules 17, no. 12: 14795-14809.