Journal
CANCER LETTERS
Volume 181, Issue 2, Pages 187-194Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/S0304-3835(02)00047-2
Keywords
colon cancer; HCT 116 cells; monoterpene; perillyl alcohol; cyclin; p21(Waf1/Cip1)
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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 p21(Waf1/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 p21(Waf1/Cip1) and the down-expression of cyclin D1 and its partner cdk4. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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