Mammary carcinoma regression induced by perillyl alcohol, a hydroxylated analog of limonene

The monoterpene perillyl alcohol has been shown to induce the regression of 81% of small mammary carcinomas and up to 75% of advanced mammary carcinomas initiated by 7,12-dimethylbenz(a)anthracene (DMBA) in the Wistar-Furth rat. Dietary perillyl alcohol was greater than 5 times more potent than the monoterpene limonene at inducing tumor regression. Perillyl alcohol is rapidly metabolized in the rat, as is limonene. Rats chronically fed perillyl alcohol had the same circulating plasma metabolites as rats fed limonene; however, the levels of these metabolites found in the plasma were higher for perillyl alcohol-fed rats. For example, rats given a 2% perillyl alcohol diet for 10 weeks had plasma levels of terpene metabolites of 0.82 mM whereas those fed a 10% limonene diet for the same period had blood levels of 0.27 mM. It thus appears that the increased potency of perillyl alcohol over limonene in causing tumor regression may be due at least in part to differences in the pharmacokinetics of these two monoterpenes. We feel that perillyl alcohol is a good candidate for clinical testing of anticancer efficacy in humans.