title: Difference in cytotoxicity of (22R)-cholest-5-ene-3 beta,7 alpha,22-triol and (22R)-cholest-5-ene-3 beta,7 beta,22-triol is not explained by different patterns of metabolites.
abstract: Ehrlich ascites tumor cells in suspension culture were incubated with the plant-derived sterol isomers (22R)-cholest-5-ene-3 beta,7 alpha,22-triol and (22R)-cholest-5-ene-3 beta,7 beta,22-triol. Both sterols were 7-dehydroxylated by the neoplastic cells, and the product was identified as (22R)-22-hydroxycholesta-4,6-dien-3-one. At sub-toxic sterol concentrations the conversion of the 7 alpha-hydroxy compound was about 5 times higher than that of the 7 beta-isomer. At higher sterol concentrations the 7 beta-hydroxy compound caused growth inhibition of the Ehrlich ascites cells, whereas the 7 alpha-hydroxylated sterol was ineffective. The rate of 7 alpha-dehydroxylation was, however, too low to be considered a likely pathway for detoxification. No other lipid-extractable products were detected, and no water-soluble products with influence on cell proliferation were present. Thus, the cytotoxicity is probably attributed to a property of the 7 beta-hydroxyl group of the (22R)-cholest-5-ene-3 beta,7 beta,22-triol.
authors.affiliation: Institute of Clinical Biochemistry, University of Oslo, Rikshospitalet, Norway.
authors.forename: K M
authors.initials: KM
authors.lastname: Boberg
authors.forename: I
authors.initials: I
authors.lastname: Smith-Kielland
authors.forename: A
authors.initials: A
authors.lastname: Stabursvik
authors.forename: O
authors.initials: O
authors.lastname: Stokke
mesh_terms: D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006888:Hydroxycholesterols / Q000378:metabolism / Q000494:pharmacology*; D008055:Lipids / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D006888:Hydroxycholesterols; D008055:Lipids; C060725:cholest-5-ene-3,7,22-triol