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Geraniol, an Inhibitor of Mevalonate Biosynthesis, Suppresses the Growth of Hepatomas and Melanomas Transplanted to Rats and Mice^1,2,

Department of Nutritional Sciences, University of Wisconsin, Madison, Madison, WI 53706

Farnesyl-pyrophosphate is required for the posttranslational modification of G proteins including p21 rats, prelamin A and lamin B, each of which plays an essential role in cell proliferation. As a consequence, competitive inhibitors of mevalonate synthesis, the rate-limiting substrate for the synthesis of the prenyl-pyrophosphates, arrest cultured cells at the G1/S interface of the cell cycle and initiate apoptotic cell death. Geraniol, an acyclic monoterpenoid alcohol, suppresses 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and concomitantly arrests the growth of cultured tumor cells. We evaluated the impact of dietary geraniol on the growth of two tumors. In the first study, geraniol (23 mmol/kg diet, 350 µmol/d) was fed to male buffalo rats for 14 d before and for 42 d after the transplant of Morris 7777 hepatomas. Tumor growth was suppressed (P < 0.001). In the second study, the dose-dependent impact of geraniol on the growth of B16 melanomas was assessed. Dietary geraniol (0.65, 6.5 and 65 mmol/kg diet) was fed to female C57BL mice for 14 d before and for 21 d after tumor transplant. Tumor growth was suppressed (P < 0.02) by 6.5 and 65 mmol geraniol/kg diet.

KEY WORDS: • mevalonate biosynthesis • tumor growth • rats • mice • chemoprevention

¹ Supported by NIH grant CA 49416 and the College of Agricultural and Life Sciences, University of Wisconsin.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ Present address: Department of Food and Nutrition, Northern Arizona University, Flagstaff, AZ 86011.

⁴ To whom correspondence should be addressed.

Manuscript received 30 January 1995. Revision accepted 10 July 1995.

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