Inhibition of ubiquinone and cholesterol synthesis by the monoterpene perillyl alcohol.
Monoterpenes such as perillyl alcohol have been shown to cause the complete regression of advanced mammary carcinomas. Given the common origin of plant monoterpenes and many important molecules in mammalian mevalonate metabolism pathway, we investigated the effects of the monoterpene perillyl alcohol on mevalonate metabolism. NIH3T3 cells were labeled with [14C]mevalonolactone and lipids were analyzed. Perillyl alcohol inhibited ubiquinone synthesis and blocked the conversion of lathosterol to cholesterol. These two cellular effects of perillyl alcohol may contribute to the antitumor activity of the monoterpenes.
Ren
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Department of Human Oncology, University of Wisconsin-Madison 53792.
Gould
M N
MN
D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000096:biosynthesis*; D002851:Chromatography, High Pressure Liquid; D008798:Mevalonic Acid / Q000378:metabolism; D051379:Mice; D039821:Monoterpenes; D013185:Squalene; D013729:Terpenes / Q000494:pharmacology*; D014451:Ubiquinone / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D039821:Monoterpenes; D013729:Terpenes; D014451:Ubiquinone; C032208:perillyl alcohol; D013185:Squalene; D002784:Cholesterol; D008798:Mevalonic Acid