Mevalonic acid as an initiator of cell growth. Studies using human lymphocytes and inhibitors of endogenous mevalonate biosynthesis.
Mevalonic acid (5 x 10(-4)-1 x 10(-2) M) stimulates DNA synthesis, morphologic transformation and cell cycling in peripheral blood human lymphocytes. Other organic acid anions which serve as cholesterol and mevalonate precursors are devoid of such effects. Both ML-236B and 25-hydroxycholesterol, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, inhibit concanavalin A-induced lymphocyte transformation, but only the inhibition by ML-236B can be overcome by exogenous mevalonate. In contrast, only 25-hydroxycholesterol inhibits mevalonate-induced lymphocyte DNA synthesis. The effects of mevalonic acid on lymphocytes cannot be reproduced by isopentenyl adenine or isopentenyl adenosine. Unregulated endogenous cellular synthesis of mevalonic acid may contribute to uncontrolled growth in certain malignant cell lines.
D003208:Concanavalin A / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000031:analogs & derivatives*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D008798:Mevalonic Acid / Q000096:biosynthesis / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology
D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D003208:Concanavalin A; C012258:mevastatin; C007997:25-hydroxycholesterol; D004247:DNA; D008148:Lovastatin; D008798:Mevalonic Acid