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

Abstract

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.

• Authors: Sylvie Bardon, Valérie Foussard, Sophie Fournel, Agnès Loubat
• Journal: Cancer letters (Cancer Lett) Vol. 181 Issue 2 Pg. 187-94 (Jul 26 2002) ISSN: 0304-3835 [Print] Ireland
• PMID: 12175534 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• CDKN1A protein, human
• Cyclin E
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins
• Cyclohexenes
• Monoterpenes
• RNA, Messenger
• Terpenes
• Cyclin D1
• perillyl alcohol
• perillic acid

Topics

• Antineoplastic Agents (pharmacology)
• Cell Division (drug effects)
• Colonic Neoplasms (drug therapy, pathology)
• Cyclin D1 (genetics)
• Cyclin E (genetics)
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins (genetics)
• Cyclohexenes
• Dose-Response Relationship, Drug
• G1 Phase (drug effects)
• Gene Expression (drug effects)
• Humans
• Monoterpenes
• RNA, Messenger (analysis)
• S Phase (drug effects)
• Terpenes (pharmacology)
• Tumor Cells, Cultured