Simvastatin and geraniol inhibits tumor growth of A549 cells implanted in nude mice

GALLE MARIANELA; SALAS MARGARITA; GARCÍA DE BRAVO MARGARITA

Potrero de los Funes, San Luis

Congreso; XLVII Reunión Anual de SAIB; 2011

SAIB

Plant isoprenoids and statins inhibit HMGCoA reductase and mevalonate pathway by different mechanisms. We have previously reported that both classes of compounds affect cholesterol synthesis and cell proliferation “in vitro”. To investigate the impact of dietary geraniol (GOH), a natural monoterpene, simvastatin (S), a statin, and their combination on lipid metabolism and growth of tumor cell “in vivo”, we implanted A549 cell line in nude mice. Animals were fed a control or experimental diet (50mmol.GOH/Kg diet; 50 ug/g body weight/day; 50mmol.GOH/Kg diet + 50 ug/g body weight/day) for 21 days after tumor implant. Tumors were measured twice a week. Three hours before sacrifice, animals were injected with 25uCi of 14C-acetate. Cholesterolemia, incorporation of radioactivity into tumor and liver lipids were determined. Tumor caspase activity and percent of apoptotic cells were measured. Tumor growth was significantly reduced by all treatments. Although serum, hepatic and tumor cholesterol did not present any differences, the incorporation of 14C-acetate into nonsaponifiable lipids was significantly decreased in GOH + S group. Moreover tumor apoptosis was induced by treatments. Our data contribute to a better understanding of the action of a common monoterpene targeting a complex metabolic pathway which would improve the use of statins in the fight against cancer