[Effects of (22S,23S)-3beta-hydroxy-22,23-oxido-5alpha-ergost-8(14)-en-15-one and (22R,23R)-3beta-hydroxy-22,23-oxido-5alpha-ergost-8(14)-en-15-one on lipid biosynthesis and exogeneous cholesterol metabolism in hep G2 cells].
Novel synthetic oxysterols (22S,23S)-3beta-hydroxy-22,23-oxido-5alpha-ergost-8(14)-en-15-one (I) and (22R,23R)-33-hydroxy-22,23-oxido-5alpha-ergost-8(14)-en-15-one (II) efficiently inhibited cholesterol biosynthesis in human hepatoma Hep G2 cell line at a short time incubation in a serum free medium (IC50 = 1.9 +/- 0.2 and 0.6 +/- 0.2 microM, respectively). Cultivation of Hep G2 cells in the presence of compound 5 microM concentration of both (1) and (II), led to significant depression of cholesterol biosynthesis (52% and 57% from control), and remarkable changes in fatty acids, triglycerides, and cholesteryl esters biosynthesis. Compounds (I) and (II) stimulated transformation of exogeneous cholesterol to polar products secreted into the culture medium (156% and 175% from control), that was shown in experiments in Hep G2 cells prelabeled with [3H]cholesterol.
Mekhtiev
A P
AP
Morozevitch
G E
GE
Ivanov
V S
VS
Misharin
A Iu
AIu
D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D013237:Stereoisomerism; D013261:Sterols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
C522916:3beta-hydroxy-22,23-oxido-5alpha-ergost-8(14)-en-15-one; D013261:Sterols; D002784:Cholesterol