RESUMEN
Farnesylacetone is a natural terpene extracted from androgenic glands of the crustacean Carcinus maenas and is capable of inhibiting proliferation, notably in transformed mammalian cells. Flow cytometry with three lipophilic probes, diphenylhexatriene, trimethylammonium-diphenylhexatriene, and Nile red, has revealed modifications of the lipidic metabolism in transformed FR3T3-mTT4 rat fibroblasts treated by farnesylacetone, including changes in membrane fluidity. Farnesylacetone strongly increased the number of neutral lipidic droplets in the cytoplasm. Moreover, after prolonged terpene treatment, the membrane fraction of cells contained a substantial level of triglycerides. Farnesylacetone provoked an immediate but transitory increase in membrane fluidity of the cell membrane. The change in measured lipid fluidity appears to be due to these triglycerides rather than to the phospholipids.
Asunto(s)
Metabolismo de los Lípidos , Fluidez de la Membrana/efectos de los fármacos , Terpenos/farmacología , Animales , Línea Celular Transformada , Membrana Celular/metabolismo , Colesterol/análisis , Citosol/metabolismo , Difenilhexatrieno/análogos & derivados , Ácidos Grasos/análisis , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Polarización de Fluorescencia , Colorantes Fluorescentes , Oxazinas , Fosfolípidos/química , Ratas , Ratas Endogámicas F344 , Temperatura , Triglicéridos/químicaRESUMEN
Farnesylacetone (C18 H30 0) is a male hormone extracted from the androgenic gland of crab, Carcinus maenas. Appropriate enzymatic assays, as well as spectrophotometric studies, indicate that micromolar concentrations of farnesylacetone interact with the electron transport pathway of rat liver mitochondria. By the use of artificial electron donors and electron acceptors, it is shown that farnesylacetone immediately inhibits the electron transfer within complex I (NADH ubiquinone reductase activity) and complex II (succinate ubiquinone reductase activity). It is proposed that farneylacetone could interact with these two complexes of the respiratory chain at the level of the iron-sulfur centers implicated in the dehydrogenase activities. These observations are compared with the results obtained with terpenic molecules which interact with mitochondrial respiration.