Molecules 2012, 17(12), 14795-14809; doi:10.3390/molecules171214795
Article

Telomerase Reverse Transcriptase (TERT) is a Therapeutic Target of Oleanane Triterpenoid CDDO-Me in Prostate Cancer

1, 1email, 1email, 2email and 1,* email
Received: 9 November 2012; in revised form: 20 November 2012 / Accepted: 6 December 2012 / Published: 11 December 2012
(This article belongs to the Special Issue Triterpenes and Triterpenoids)
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.
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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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.

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