Abstract: Effects of 3β-hydroxy-5α-cholest-8(14)-en-15-one (I), 3α-hydroxy-5α-cholest-8(14)-en-15-one (II), 3β-hexadecanoyloxy-5α-cholest-8(14)-en-15-one (III), 3α-hehadecanoyloxy-5a-cholest-8(14)-en-15-one (IV), 3β-acetoxy-5α-cholest-8(14)-en-15-one (V), 3α-acetoxy-5α-cholest-8(14)-en-15-one (VI) on cholesterol metabolism in hepatoma Hep G2 cells were studied. Compound III slowly bind to Hep G2 cells followed by internalization and metabolic transformation (at a concentration of 30 µM the total binding of compound III was (3.9±0.4) nmol per 1 mg of cell protein for 24 h incubation). Compound I depressed and compound III stimulated the uptake of low density lipoproteins radiolabeled with oleyl cholesteryl ether [14C-CE]LDL (58% and 149% from control). Compounds I and II inhibited cholesterol biosynthesis from [14C]аcetate (with IC50 values of 4.0±0.7 and 8.0±1.5 µМ). Effects of compounds V and VI were less potent; compounds III and IV were inactive. Compound II activated cholesterol acylation, estimated by incorporation of [14C]-oleic acid into cholesteryl esters (170% from control at a concentration of 30 µМ). The results indicate correlation between polarity of the compound and its ability to regulate cholesterol metabolism in Hep G2 cells.
Reference: Piir E.A., Medvedeva N.V., Kashirina N.M., Shevelev A.Ya., Misharin A.Yu., Interaction of acyl derivatives of 3β-hydroxy-5α-cholest-8(14)-en-15-one and 3α-hydroxy-5a-cholest-8(14)-en-15-one with hepatoma Hep G2 cells, Biomeditsinskaya khimiya, 2004, vol: