[Interaction of acyl derivatives of 3beta-hydroxy-5alpha-cholest-8(14)-en-15-one and 3alpha-hydroxy-5alpha-cholest-8(14)-en-15-one with hepatoma hep G2 cells].
Effects of 3beta-hydroxy-5alpha-cholest-8(14)-en-15-one (I), 3alpha-hydroxy-5alpha-cholest-8(14)-en-15 one (II), 3beta-hexadecanoyloxy-5alpha-cholest-8(14)-en-15-one (III), 3alpha-hehadeeanoyloxy-5alpha-cholest-8(14)-en-15-one (IV), 3beta-acetoxy-5alpha-cholest-8(14)-en-15-one (V), 3alpha-acetoxy-5alpha-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 microM 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]acetate (with IC50 values of 4.0 +/- 0.7 and 8.0 +/- 1.5 microM). 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 microM). The results indicate correlation between polarity of the compound and its ability to regulate cholesterol metabolism in Hep G2 cells.
Piĭr
E A
EA
Medvedeva
N V
NV
Kashirina
N M
NM
Shevelev
A Ia
AIa
Misharin
A Iu
AIu
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002783:Cholestenones / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis; D004705:Endocytosis; D006801:Humans
D002783:Cholestenones; D002784:Cholesterol