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

2002; Elsevier BV; Volume: 181; Issue: 2 Linguagem: Inglês

10.1016/s0304-3835(02)00047-2

1872-7980

Sylvie Bardon, Valérie Foussard, Sophie Fournel, Agnès Loubat,

Cancer, Lipids, and Metabolism

The monoterpene perillyl alcohol (POH) is a naturally occurring anti-cancer compound which is effective against a variety of rodent organ-specific tumor models. To establish the molecular mechanisms of POH and its major metabolite perillic acid (PA) as anti-proliferative agents, their effects on cell proliferation, cell cycle and cell cycle regulatory proteins were studied in HCT 116 human colon cancer cells. POH, and to a lesser extent, PA, exerted a dose-dependent inhibitory effect on cell growth correlated with a G1 arrest. Analysis of G1 cell cycle regulators expression revealed that monoterpenes increased expression of cdk inhibitor p21Waf1/Cip1 and cyclin E, and decreased expression of cyclin D1, cyclin-dependent kinase (cdk) 4 and cdk2. Our results suggest that monoterpenes induce growth arrest of colon cancer cells through the up-regulation of p21Waf1/Cip1 and the down-expression of cyclin D1 and its partner cdk4.