Geraniol regulates HMG CoA reductase at a transcriptional level in Hep G2

CRESPO R; POLO M; GARCÍA DE BRAVO MM

Potrero de los Funes

Congreso; XLVII Reunión Anual de SAIB; 2011

SAIB

Plant isoprenoids, a broad class of plant products derived from the mevalonate pathway are widely distributed in fruits and vegetables. It has been suggested that these compounds suppress the growth of cancer cells and development through multiple effects on mevalonate pathway. We have reported that geraniol (G), a natural monoterpene, inhibits cholesterol synthesis and cell growth at concentration greater than 10 µM and 100 µM respectively in HepG2 cells. We also reported that 50 µM G inhibit the conversion of lanosterol into cholesterol. The aim of this study was to analyze the mechanism through which G exerts these effects on the mevalonate pathway in human liver cells. We studied the expression of the HMGCoA reductase and SREBP2 genes in cells incubated at different times with 50µM and 200µM G. HMGCoA reductase levels were determined by western blot and enzyme activity was measured. At 4 h G treatment, real time PCR revealed that the expression of genes was reduced in a dose dependent manner. Consequently, a decrease in quantity and activity of the enzyme and a reduction in cholesterol levels were observed at 24 h. This induces an increase in the enzyme expression. These results suggest that geraniol decreases cholesterol synthesis by transcriptional inhibition of HMGCoA reductase in a direct or indirectly way, and by inhibiting the conversion of lanosterol to cholesterol.