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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
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Telomerase reverse transcriptase (TERT) is a therapeutic target of oleanane triterpenoid CDDO-Me in prostate cancer

Yongbo Liu1, Xiaohua Gao, Dorrah Deeb

  • 1Department of General Surgery, Henry Ford Health System, Detroit, MI 48202, USA.

Molecules (Basel, Switzerland)
|March 23, 2013
PubMed

Insights

Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) inhibits prostate cancer growth by targeting human telomerase reverse transcriptase (hTERT). This study reveals hTERT as a key mediator of CDDO-Me

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Synthetic oleanane triterpenoid Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) exhibits potent anti-cancer properties.
  • The impact of CDDO-Me on human telomerase reverse transcriptase (hTERT) and its activity in prostate cancer remains uninvestigated.

Purpose of the Study:

  • To elucidate the role of hTERT in mediating the anti-cancer effects of CDDO-Me.
  • To investigate the in vitro and in vivo efficacy of CDDO-Me in prostate cancer models.

Main Methods:

  • Assessed CDDO-Me's effects on prostate cancer cell lines (LNCaP, PC-3) and TRAMP mice.
  • Quantified hTERT gene expression, telomerase activity, and regulatory protein levels.
  • Utilized gene ablation and overexpression techniques to study hTERT's role.

Main Results:

  • CDDO-Me inhibited proliferation and induced apoptosis in prostate cancer cells, correlating with decreased hTERT expression and activity.
  • hTERT ablation sensitized cells to CDDO-Me, while overexpression conferred resistance.
  • In TRAMP mice, CDDO-Me suppressed prostate intraepithelial neoplasia progression, linked to reduced TERT and regulatory proteins.

Conclusions:

  • Telomerase (hTERT) is a critical mediator of CDDO-Me's anti-cancer activity in prostate cancer.
  • CDDO-Me demonstrates potential as a therapeutic agent targeting telomerase for prostate cancer prevention and treatment.

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