Simvastatin shows a synergistic effect with geraniol on HeP G2 cells

POLO M; BELLINI MJ; BRAVO MG DE

Villa Carlos Paz, Argentina

Congreso; XXXVIII Anual Meeting of SAIB; 2002

SAIB

Simvastatin is a competitive inhibitor of HMG-CoA reductase activity whereas geraniol is a monoterpene with multiple pharmacologic effects on mevalonate metabolism. Both of them inhibit growth and proliferation of many cell lines, however the inhibitory dose of simvastatin is toxic to normal cells. We have previously reported that geraniol up 100 mM diminishes growth, HMG-CoA reductase activity and the conversion of lanosterol into cholesterol of Hep G2 cells. The possibility that geraniol could potentiate the inhibitory effect of simvastatin used in subliminal concentration was tested. To study the effect of simvastatin on Hep G2 cell  proliferation, cells were cultured in the presence of simvastatin (0-20 mM). After 48h. cell numbers, cholesterol and phosphorus content were determined. Simvastatin up 10 mM causes 40% inhibition on the growth rate with an increment in phosphorus/cholesterol ratio. To test the effect of the combination of both inhibitors on Hep G2 cell proliferation, cells were cultured in the presence of Simvastatin + geraniol  for 48 h. The addition of either 5mM simvastatin or 50mM geraniol did not significantly inhibit Hep G2 cell proliferation, while their combination inhibited by 35% the growth rate of  this cell line. These results demostrated a sinergistic effect of the combination of a statin and a nonnutritive dietary component wich would provide a new appoach to chemotheraphy and hypercholesterolemic treatment.