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Updated: May 19, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

The isoprenoid perillyl alcohol inhibits telomerase activity in prostate cancer cells

Tabetha Sundin1, Dennis M Peffley, David Gauthier

  • 1Department of Biological Sciences, Old Dominion University, Norfolk, VA 23529, USA.

Biochimie
|August 21, 2012
PubMed

Insights

Perillyl alcohol and rapamycin rapidly suppress telomerase activity in prostate cancer cells by reducing hTERT protein levels via proteasomal degradation, not affecting hTERT mRNA.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Isoprenoids, like perillyl alcohol, can suppress cancer development.
  • Mechanistic target of rapamycin (mTOR) signaling is modulated by perillyl alcohol.
  • Telomerase is reactivated in early-stage cancer cells, contributing to cellular immortality.

Purpose of the Study:

  • To investigate the effects of perillyl alcohol and an mTOR inhibitor, rapamycin, on telomerase activity in prostate cancer cells.
  • To elucidate the molecular mechanisms underlying changes in telomerase activity.

Main Methods:

  • Treatment of prostate cancer cell lines with perillyl alcohol or rapamycin.
  • Assay of telomerase activity using quantitative telomerase repeat amplification protocol and polyacrylamide gel electrophoresis.
  • Analysis of human telomerase reverse transcriptase (hTERT) mRNA and protein levels via real-time RT-PCR and Western blot.
  • Investigation of proteasomal degradation involvement using MG-132.

Main Results:

  • Rapid and significant suppression of telomerase activity (65% to >95%) was observed with both perillyl alcohol and rapamycin.
  • hTERT mRNA levels remained unchanged, but hTERT protein levels decreased.
  • Proteasome inhibitor MG-132 partially blocked the decrease in hTERT protein, indicating proteasomal degradation.
  • No alteration in hTERT phosphorylation at Ser824 was detected.

Conclusions:

  • Perillyl alcohol and rapamycin effectively reduce telomerase activity in prostate cancer cells.
  • The mechanism involves increased proteasomal degradation of hTERT protein, independent of hTERT mRNA levels or phosphorylation.
  • This study reveals a novel link between mTOR signaling and hTERT regulation, impacting DNA stability in cancer.

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