Monoterpenes inhibit proliferation of human colon cancer cells by modulating cell cycle-related protein expression.
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.
Bardon
Sylvie
S
Laboratoire de Nutrition et Sécurité Alimentaire,UR909, INRA, 78352 cedex, Jouy-en-Josas, France. bardon@unice.fr
Foussard
Valérie
V
Fournel
Sophie
S
Loubat
Agnès
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics; D019927:Cyclin E / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D053138:Cyclohexenes; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D039821:Monoterpenes; D012333:RNA, Messenger / Q000032:analysis; D016196:S Phase / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D053138:Cyclohexenes; D039821:Monoterpenes; D012333:RNA, Messenger; D013729:Terpenes; D019938:Cyclin D1; C032208:perillyl alcohol; C078706:perillic acid