Antagonist action of cholesterol towards the toxicity of hydroxysterols on cultured hepatoma cells.
The cytostatic and cytolytic action of 22R - hydroxydesmosterol on hepatoma cells cultured in a medium containing 10% newborn-calf serum can be reversed within certain concentration limits by adding cholesterol to the culture medium. In contrast, under the same conditions, the cytotoxicity of 7 beta -hydroxycholesterol could not be reversed, whatever the concentrations of cholesterol added. However, in a lipoprotein-poor and in a chemically defined medium, the cytolytic action of both hydroxysterols can be reversed by adding cholesterol, but growth inhibition cannot be suppressed. This demonstrates the importance of serum lipids and lipoproteins for the toxicity of the hydroxysterols and for the antagonistic effect of cholesterol. Our results suggest that the action mechanisms of 7 beta-hydroxycholesterol and 22R - hydroxydesmosterol on HTC hepatoma cells are not fully identical.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology*; D003470:Culture Media; D003897:Desmosterol / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D006888:Hydroxycholesterols / Q000037:antagonists & inhibitors*; D008055:Lipids / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D051381:Rats
D003470:Culture Media; D006888:Hydroxycholesterols; D008055:Lipids; D003897:Desmosterol; C022238:22(R)-hydroxydesmosterol; C011724:cholest-5-en-3 beta,7 alpha-diol; D002784:Cholesterol