CONICET | Buscador de Institutos y Recursos Humanos

Monoterpenes have multiple pharmacological effects on the metabolism of mevalonate. Geraniol, a dietary monoterpene, has in vitro and vivo antitumor activity against several cell lines. We have studied the effects of geraniol on the growth and fatty acid and mevalonate metabolism in the human hepatocarcinoma cell line Hep G2. Up to 100 mM geraniol inhibited the growth rate and HMG-CoA reductase activity of these cells. At the same concentrations it increased the incorporation of cholesterol from the medium in a dose-dependent manner. Geraniol-treated cells incorporated less 14C-acetate into nonsaponifiable lipids, inhibiting its incorporation into cholesterol but not into squalene and lanosterol. This was indicative of an inhibition in the cholesterol synthesis at a step between lanosterol and cholesterol, fact confirmed when cells were incubated with 3H-mevalonate. The incorporation of 3H-mevalonate into protein was also inhibited whereas its incorporation into fatty acid was increased. An inhibition of Ä5 desaturase activity was demonstrated by the inhibition of the conversion of 14C-dihomo-ã-linolenic acid into arachidonic acid. Geraniol has multiple effects on mevalonate and lipid metabolism in Hep G2 cells, affecting cell proliferation. Although mevalonate depletion would not be responsible for cellular growth, it affects cholesterogenesis, protein prenylation and fatty acid metabolism.