Mevalonate metabolism in A-549 cells growth in athymic mice: effects of geraniol

BELLINI MJ.; POLO M; MASCHI, FABRICIO; BELLINI MJ., POLO M; ALANIZ MJT DE, BRAVO MG DE; BRAVO MG DE.

Villa Carlos Paz, Argentina

Congreso; XXXVIII Anual Meeting of SAIB; 2002

SAIB

Products of plant mevalonate metabolism, like geraniol supress tumor cell proliferation. To investigate the impact of dietary geraniol on the uptake and distribution of mevalonate and growth of tumor cells “in-vivo”, we implanted A549 cell line in nude mice. Animals were fed a control or experimental (60 mmol.geraniol/kg diet) diet 14 days before and after tumor implant. On day 64 and therafter mice with tumor estimated to be 500 mm3 or larger were killed and tumors, lungs, hearts, livers and kidneys removed. 24h before sacrifice, animals were injected with 30 µCi de 3H-Mevalonolactone. Aliquots from tissues were precipitated with TCA, pellets were delipidated and proteics, lipidics and aqueous fractions were obtained and analyzed for radioactivity. Total lipids were extracted according to Folch and saponified. Nonsaponificable lipids were separated by TLC and recovered for radioactivity measurement. Geraniol and tumor increased the uptake of mevalonate and modified its metabolization in different tissues. Kidney presented the highest incorporation (10% vs 0.4-2%). Most of the radioactivity was found in lipidic fractions (~ 85%).  Proteic fraction of kidney showed 13% of radioactivity vs.1-6 % in other tissues.The distribution in hepatic nonsaponificable lipids was modified by treatment and by tumor. Dietary geraniol did not affect tumor growth but clearly altered mevalonate uptake and distribution of mevalonate.