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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Authors: | Piir E. A. Medvedeva N. V. Kashirina N. M. Shevelev A. Ya. Misharin A. Yu. |
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Affiliation: | (1) Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya ul. 10, Moscow, 119992, Russia;(2) Institute of Experimental Cardiology, Cardiology Research Center, Ministry of Health of the Russian Federation, Moscow, Russia |
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Abstract: | The effect on cholesterol metabolism in Hep G2 hepatoma cells was studied for new analogues of 15-ketosterol [3-hydroxy-5-cholest-8(14)-en-15-one] (I): (24S)-3-hydroxy-24-methyl-5-cholesta-8(14),22-diene-15-one (II), (24S)-3-hydroxy-24-methyl-5-cholesta-8(14),22-diene-15-one (III), and (24S)-24-methyl-5-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 M and exerted no marked effect at a concentration of 30 M. These results indicate that 8(14)-15-ketosterols containing a modified side chain are of interest as regulators of cholesterol metabolism in liver cells. |
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Keywords: | cholesterol metabolism Hep 2G hepatoma cells inhibitors of cholesterol biosynthesis oxysterols |
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