title: Oxidized derivatives of dihydrobrassicasterol: cytotoxic and apoptotic potential in U937 and HepG2 cells.
abstract: The ability of phytosterol compounds to reduce plasma serum cholesterol levels in humans is well investigated. However, phytosterols are structurally similar to cholesterol with a double bond at the C5-6 position and are therefore susceptible to oxidation. Much research has been carried out on the biological effects of cholesterol oxidation products (COPs) in vitro. In contrast, there is less known about phytosterol oxidation products (POPs). From previous studies, it is apparent that oxidized derivatives of the phytosterols, β-sitosterol and stigmasterol, are cytotoxic in vitro but are less potent than their COP counterparts. In the present study, the cytotoxic and apoptotic potential of oxidized derivatives of dihydrobrassicasterol (DHB) including 5α,6α-epoxyergostan-3β-ol (α-epoxide), 5β,6β-epoxyergostan-3β-ol (β-epoxide), ergost-5-en-7-on-3β-ol (7-keto), ergost-5-ene-3β,7β-diol (7-β-OH), and ergostane-3β,5α,6β-triol (triol) were evaluated in the U937 and HepG2 cell lines. In general, 7-keto, 7-β-OH, and triol derivatives had a significant cytotoxic impact on U937 and HepG2 cells. The oxides appear to be more toxic toward U937 cells. In line with previous findings, the POPs investigated in this study were less potent than the equivalent COPs. The results add to the body of data on the toxicity of individual POPs.
authors.affiliation: School of Food and Nutritional Sciences, ‡Department of Chemistry, Analytical and Biological Chemistry Research Facility, and §School of Pharmacy, Analytical and Biological Chemistry Research Facility, University College Cork , Cork, Ireland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Kenny
authors.forename: Yvonne
authors.initials: Y
authors.lastname: O'Callaghan
authors.forename: Niamh M
authors.initials: NM
authors.lastname: O'Connell
authors.forename: Florence O
authors.initials: FO
authors.lastname: McCarthy
authors.forename: Anita R
authors.initials: AR
authors.lastname: Maguire
authors.forename: Nora M
authors.initials: NM
authors.lastname: O'Brien
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D053938:DNA Fragmentation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects; D010840:Phytosterols / Q000737:chemistry* / Q000494:pharmacology; D012855:Sitosterols / Q000737:chemistry* / Q000494:pharmacology; D013265:Stigmasterol / Q000737:chemistry* / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D010840:Phytosterols; D012855:Sitosterols; C025473:gamma-sitosterol; D002784:Cholesterol; D013265:Stigmasterol; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7