Potentiated cytotoxic effects of statins and ajoene in murine melanoma cells.
Because statins and ajoene inhibit the 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, we evaluated the hypothesis that the cytotoxic effect of these compounds may be potentiated when both are used in combination on tumor cells. We showed that cotreatment of the murine melanoma B16F10 cell with statins (atorvastatin and pravastatin) and ajoene, all at nontoxic doses, dramatically increased their cytotoxicity. B16F10 cell death induced by statins, but not by ajoene, was prevented by mevalonate and geranylgeranylpyrophosphate. To our knowledge, this is the first report that the combination of statins and ajoene, which alters the mevalonate pathway, might potentiate their cytotoxic effects on tumor cells.
Ledezma
Eliades
E
Fundacite, Estado Trujillo, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas, Apartado, Caracas, Venezuela.
Wittig
Olga
O
Alonso
Jose
J
Cardier
Jose E
JE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin; D045744:Cell Line, Tumor / Q000187:drug effects; D004220:Disulfides / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005434:Flow Cytometry; D006538:Heptanoic Acids / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008544:Melanocytes / Q000187:drug effects*; D008546:Melanoma, Experimental / Q000473:pathology*; D008798:Mevalonic Acid / Q000494:pharmacology; D051379:Mice; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology; D017035:Pravastatin / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D013454:Sulfoxides; D013729:Terpenes / Q000378:metabolism
D004220:Disulfides; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011106:Polyisoprenyl Phosphates; D011758:Pyrroles; D013454:Sulfoxides; D013729:Terpenes; C048980:ajoene; D000069059:Atorvastatin; D017035:Pravastatin; C002963:geranylgeranyl pyrophosphate; D008798:Mevalonic Acid