Next Article in Journal
Microbial Transformations of 7-Methoxyflavanone
Next Article in Special Issue
Antiprotozoal Activity of Quinonemethide Triterpenes from Maytenus ilicifolia (Celastraceae)
Previous Article in Journal
Purification and Characterization of a Novel ~18 kDa Antioxidant Protein from Ginkgo biloba Seeds
Previous Article in Special Issue
New Triterpenes from Maytenus robusta: Structural Elucidation Based on NMR Experimental Data and Theoretical Calculations
Article Menu

Article Versions

Export Article

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

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

1
Department of General Surgery, Henry Ford Health System, Detroit, MI 48202, USA
2
Department of Radiology, Henry Ford Health System, Detroit, MI 48202, USA
*
Author to whom correspondence should be addressed.
Received: 9 November 2012 / Revised: 20 November 2012 / Accepted: 6 December 2012 / Published: 11 December 2012
(This article belongs to the Special Issue Triterpenes and Triterpenoids)
Download PDF [822 KB, uploaded 18 June 2014]

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 CDDO-Me; hTERT; telomerase activity; apoptosis; prostate cancer
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

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.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top