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Concentration-dependent Increase of Murine P388 and B16 Population Doubling Time by the Acyclic Monoterpene Geraniol¹

Departments of Nutritional Sciences [S.M.S., M.G., C.E.E.] and Human Oncology [M.B.Y.], University of Wisconsin, Madison, Wisconsin 53706

Geraniol, an acyclic end product of a plant isoprene pathway and a pyrophosphorylated intermediate in plant and animal pathways, caused a concentration-dependent increase in the population doubling time of murine P388 leukemia cells in suspension culture and of B16 melanoma cells in monolayer culture. The suppression of the growth of P388 cells by geraniol (0–0.9 mM) and by mevinolin (0–0.25 µM), a competitive inhibitor of mevalonate biosynthesis, was reversed by the addition of 0.5 mM mevalonolactone to the growth medium. Flow cytometry of asynchronous B16 cells grown with geraniol (0–0.15 mM) revealed a population characterized by larger cells with altered nuclear characteristics. Over the course of four studies, dietary geraniol increased the 50% survival time of mice by 10, 29, 33, and 50% following the i.p. transfer of P388 cells. The results of the latter study showed that, following the i.p. transfer of 1 x 10⁵ P388 cells, the control group of female C57BL x DBA/2 F₁ mice had a 50% survival time of 24 days and a maximum survival of 27 days. Mice fed a diet containing 0.1% geraniol for 14 days prior to and following the P388 cell transfer had a 50% survival time of 36 days, and 20% of the mice remained free of tumors during the 50-day trial. These studies support the possibility that monoterpenes and other isoprenoid products of plant metabolism are in part responsible for the anticarcinogenic actions of diverse fruits, vegetables, and cereal products.

¹ Supported in part by USPHS Grants HL 33893 and CA 09451 and by the College of Agricultural and Life Sciences, University of Wisconsin-Madison.

² Present address: Department of Radiation Oncology, Oregon Health Sciences University, Portland, OR 97201.

³ To whom requests for reprints should be addressed, at Department of Nutritional Sciences, University of Wisconsin, 1415 Linden Drive, Madison, WI 53706.

Received 5/25/90. Accepted 10/ 8/90.

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