ACTION OF LOVASTATIN, SIMVASTATIN, AND PRAVASTATIN ON STEROL SYNTHESIS AND THEIR ANTIPROLIFERATIVE EFFECT IN CULTURED MYOBLASTS FROM HUMAN STRIATED-MUSCLE

Lovastatin, simvastatin, and pravastatin are fairly strong inhibitors of sterol synthesis in human myoblasts in culture. Lovastatin and simv astatin have IC50 values of 19 +/- 6 nM and 4.0 +/- 2.3 nM, respective ly. Pravastatin is a weaker inhibitor of sterol synthesis (IC50 value of 110 +/- 38 nM). Through inhibition of mevalonate production, these compounds have a distinct inhibiting effect on cell proliferation. Bec ause proliferation of myoblasts is important in the repair of damaged skeletal muscle, experiments were performed to investigate the effect of lovastatin, simvastatin, and pravastatin on cell proliferation and cell viability. The more potent inhibitors of sterol synthesis, lovast atin, and simvastatin, were able to inhibit the proliferation of these cells during 3 days of incubation with drug concentrations of 1 mu M for lovastatin and 0.1 mu M or 1 mu M for simvastatin. DNA synthesis w as decreased by more than 80% in the presence of 1 mu M of lovastatin or simvastatin. In contrast, under these conditions, pravastatin had n o influence on cell proliferation or DNA synthesis, which is probably related to the lack of inhibition of sterol synthesis by pravastatin o n extended incubation. The three 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors did not disturb cell viability because mitochond rial dehydrogenase activity and ATP content remained proportional to t he number of cells in the culture at any concentration used. Copyright (C) 1996 Elsevier Science Inc.