Effect of geraniol on fatty-acid and mevalonate metabolism in the human hepatoma cell line Hep G2.
Monoterpenes have multiple pharmacological effects on the metabolism of mevalonate. Geraniol, a dietary monoterpene, has in vitro and in vivo anti-tumor activity against several cell lines. We have studied the effects of geraniol on growth, fatty-acid metabolism, and mevalonate metabolism in the human hepatocarcinoma cell line Hep G2. Up to 100 micromol geraniol/L inhibited the growth rate and 3-hydroxymethylglutaryl coenzyme A reductase (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 is indicative of an inhibition in cholesterol synthesis at a step between lanosterol and cholesterol, a 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 increased. An inhibition of delta5 desaturase activity was demonstrated by the inhibition of the conversion of 14C-dihomo-gamma-linolenic acid into arachidonic acid. Geraniol has multiple effects on mevalonate and lipid metabolism in Hep G2 cells, affecting cell proliferation. Although mevalonate depletion is not responsible for cellular growth, it affects cholesterogenesis, protein prenylation, and fatty-acid metabolism.
Polo
Monica P
MP
Instituto de Investigaciones Bioquímicas de La Plata, UNLP-CONICET Facultad de Ciencias Médicas, UNLP, Argentina.
de Bravo
Margarita G
MG
D000085:Acetates / Q000378:metabolism; D000080462:Acyclic Monoterpenes; D002250:Carbon Radioisotopes; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D005223:Fats / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent / Q000378:metabolism; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000085:Acetates; D000080462:Acyclic Monoterpenes; D002250:Carbon Radioisotopes; D005223:Fats; D005227:Fatty Acids; D010743:Phospholipids; D013729:Terpenes; D010758:Phosphorus; C015367:mevalonolactone; D002784:Cholesterol; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; C007836:geraniol; D008798:Mevalonic Acid