The Effect of 15-Ketosterol Analogues with a 5,6-Dimethylhept-3-en-2-yl Chain at C17 on Cholesterol Metabolism in Hep G2 Hepatoma Cells

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The effect on cholesterol metabolism in Hep G2 hepatoma cells was studied for new analogues of 15-ketosterol [3β-hydroxy-5α-cholest-8(14)-en-15-one] (I): (24S)-3β-hydroxy-24-methyl-5α-cholesta-8(14),22-diene-15-one (II), (24S)-3α-hydroxy-24-methyl-5α-cholesta-8(14),22-diene-15-one (III), and (24S)-24-methyl-5α-cholesta-8(14),22-diene-3,15-dione (IV). Analogues (I) and (II) were found to be equally effective inhibitors of cholesterol biosynthesis after a 3-h incubation with Hep G2 cells; however, (II) produced a stronger inhibitory effect after a 24-h incubation or after an incubation of cells preliminarily treated with the inhibitor in a medium containing no ketosterol. The ability of ketosterols to inhibit cholesterol biosynthesis decreased in the order (II) > (IV) > (III). Ketosterol (II) inhibited, whereas ketosterol (III) stimulated the biosynthesis of cholesteryl esters. (IV) stimulated the biosynthesis of cholesteryl esters at a concentration of 1-10 μM and exerted no marked effect at a concentration of 30 μM. These results indicate that Δ8(14)-15-ketosterols containing a modified side chain are of interest as regulators of cholesterol metabolism in liver cells.

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