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Monoterpenes inhibit proliferation of human colon cancer cells by modulating cell cycle-related protein expression

Sylvie Bardon1, Valérie Foussard, Sophie Fournel

  • 1Laboratoire de Nutrition et Sécurité Alimentaire,UR909, INRA, 78352 cedex, Jouy-en-Josas, France. bardon@unice.fr

Cancer Letters
|August 15, 2002
PubMed

Insights

Perillyl alcohol (POH) and perillic acid (PA) inhibit colon cancer cell growth by arresting the cell cycle. These natural compounds up-regulate p21(Waf1/Cip1) and down-regulate cyclin D1 and cdk4.

Area of Science:

  • Oncology
  • Molecular Biology
  • Natural Products Chemistry

Background:

  • Perillyl alcohol (POH) is a naturally occurring monoterpene with demonstrated anti-cancer efficacy in various rodent tumor models.
  • Understanding the molecular mechanisms of POH and its metabolite perillic acid (PA) is crucial for their therapeutic development.

Purpose of the Study:

  • To investigate the anti-proliferative effects of POH and PA on HCT 116 human colon cancer cells.
  • To elucidate the impact of these monoterpenes on cell cycle progression and the expression of key cell cycle regulatory proteins.

Main Methods:

  • HCT 116 human colon cancer cells were treated with varying doses of POH and PA.
  • Cell proliferation was assessed, and cell cycle distribution was analyzed.
  • Expression levels of G1 cell cycle regulators, including cyclins and cyclin-dependent kinases (cdks), were determined.

Main Results:

  • POH and, to a lesser extent, PA exhibited a dose-dependent inhibition of colon cancer cell growth.
  • Treatment with these monoterpenes resulted in a G1 phase cell cycle arrest.
  • Key molecular changes included increased expression of p21(Waf1/Cip1) and cyclin E, alongside decreased expression of cyclin D1, cdk4, and cdk2.

Conclusions:

  • Monoterpenes POH and PA induce growth arrest in human colon cancer cells.
  • The observed anti-proliferative effect is mediated through the up-regulation of p21(Waf1/Cip1) and the down-regulation of the cyclin D1/cdk4 complex.

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