title: Geraniol, an inhibitor of mevalonate biosynthesis, suppresses the growth of hepatomas and melanomas transplanted to rats and mice.
abstract: Farnesyl-pyrophosphate is required for the posttranslational modification of G proteins including p21 ras, 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 mumol/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.
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology*; D008798:Mevalonic Acid / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D051381:Rats; D011915:Rats, Inbred BUF; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology*; D013729:Terpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D000080462:Acyclic Monoterpenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013729:Terpenes; C007836:geraniol; D008798:Mevalonic Acid