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  • Title: Effect of a hypocholesterolemic agent on cholesteryl ester metabolism in glioblastoma cells.
    Author: Jeng I, Klemm N, Samson L.
    Journal: Biochem Pharmacol; 1985 Apr 15; 34(8):1305-9. PubMed ID: 3994747.
    Abstract:
    The hypocholesterolemic agent 3 beta-(2-diethylaminoethoxy)androst-5-en-17-one . HCl (U18666A) is known to induce experimental epilepsy. The possibility that this drug interferes with cholesteryl ester formation in glioblastoma cells was examined. The incorporation of radioactive oleic acid into cellular cholesteryl ester was drastically and specifically inhibited by U18666A. The inhibitory effect of U18666A persisted in different oleic acid concentrations. Kinetic studies revealed the rapidity of U18666A action. U18666A was found to be ineffective in inhibiting acyl-CoA:cholesterol acyltransferase activity when it was added directly to the cell homogenates. In contrast, the acyltransferase activity was greatly diminished in homogenates derived from U18666A-treated cells. Thus, U18666A appeared to block cellular cholesteryl ester biosynthesis by indirectly inactivating acyl-CoA:cholesterol acyltransferase activity in a cell-dependent manner. The potent inhibition of cholesteryl ester formation by U18666A represents one unique aspect of the drug which might contribute to its ability to induce chronic epileptiform activity.
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