EFFICACY OF BETA-IONONE IN THE CHEMOPREVENTION OF RAT MAMMARY CARCINOGENESIS

Secondary products of plant mevalonate metabolism suppress the synthesis of mevalonate, the rate-limiting substrate for the synthesis of isoprenoid intermediates essential for cell proliferation. d-Limonene is an effective anticarcinogen when tested with chemical carcinogens. This monoterpene also causes the regression of chemically established tumors. Geraniol suppresses the growth of transplanted tumors. The potency of beta-ionone in suppressing 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity exceeds that of either monoterpene. In parallel trials, the efficacies of equimolar intakes (36 mmol/kg of diet) of d-limonene and geraniol were compared with that of beta-ionone in the chemoprevention of 7,12-dimethylbenz[a]anthracene-initiated mammary cancer. The monoterpenes decreased tumor multiplicity by 45% (P < 0.001), The impact of beta-ionone on tumor multiplicity was similar to 2x that of the monoterpenes (P < 0.001). Tumor incidence and latency were affected to varying degrees. The locus of the action of the isoprenoids is postulated to be in the suppression of the sterol-resistant HMGR activity, which is characteristic of neoplastic cells. Dietary guidelines advocate the consumption of fruits, vegetables, and cereal grains, the major sources of diverse isoprenoids.