Inhibition of cell growth by oxygenated derivatives of cholesterol

CELLS growing in a chemically defined, sterol-free medium must synthesise cholesterol or, in the case of L cells, desmosterol 1 for membrane formation. Studies by others showed that when cholesterol or desmosterol was added to L-cell cultures the exogenous sterol was utilised and the rate of sterol...

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Bibliographic Details
Published in:Nature (London) 1974-10, Vol.251 (5474), p.419-421
Main Authors: CHEN, HARRY W, KANDUTSCH, ANDREW A, WAYMOUTH, CHARITY
Format: Article
Language:English
Subjects:
Acetates - pharmacology
Alcohol Oxidoreductases - metabolism
Animals
Cell Division - drug effects
Cholesterol - analogs & derivatives
Cholesterol - pharmacology
Chromatography, Gas
Depression, Chemical
Desmosterol - analysis
Desmosterol - biosynthesis
Enzyme Repression - drug effects
Humanities and Social Sciences
Hydroxycholesterols - pharmacology
L Cells (Cell Line) - metabolism
letter
Mevalonic Acid - pharmacology
Mice
multidisciplinary
Science
Science (multidisciplinary)
Sitosterols - pharmacology
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Summary:CELLS growing in a chemically defined, sterol-free medium must synthesise cholesterol or, in the case of L cells, desmosterol 1 for membrane formation. Studies by others showed that when cholesterol or desmosterol was added to L-cell cultures the exogenous sterol was utilised and the rate of sterol synthesis was diminished, presumably by a negative feedback mechanism 2,3 . Our observations 4 , however, provide new information regarding the structures of sterols that affect sterol synthesis. Exogenous cholesterol and various metabolically related steroids do not inhibit sterol synthesis in mouse liver cell or fibroblast cultures under conditions where derivatives of cholesterol oxygenated in the 7, 20, 22 or 25 positions are highly inhibitory. These inhibitory sterols, at concentrations of 0.02–0.2 µ g ml −1 specifically depress the activity of the regulatory enzyme in the sterol synthetic pathway, 3-hydroxy-3-methylgrutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34), within 6 h.
ISSN:0028-0836
1476-4687
DOI:10.1038/251419a0