title: Lack of genoprotective effect of phytosterols and conjugated linoleic acids on Caco-2 cells.
abstract: Much interest has focused on the cholesterol-lowering effects of phytosterols (plant sterols) but limited data suggests they may also possess anti-carcinogenic activity. Conjugated linoleic acids (CLA), sourced from meat and dairy products of ruminant animals, has also received considerable attention as a potential anti-cancer agent. Therefore, the aims of this project were to (i) examine the effects of phytosterols and CLA on the viability and growth of human intestinal Caco-2 cells and (ii) determine their potential genoprotective (comet assay), COX-2 modulatory (ELISA) and apoptotic (Hoechst staining) activities. Caco-2 cells were supplemented with the phytosterols campesterol, beta-sitosterol, or beta-sitostanol, or a CLA mixture, or individual CLA isomers (c10t12-CLA, t9t11-CLA) for 48 h. The three phytosterols, at the highest levels tested, were found to reduce both the viability and growth of Caco-2 cells while CLA exhibited isomer-specific effects. None of the phytosterols protected against DNA damage. At a concentration of 25 microM, both c10t12-CLA and t9t11-CLA enhanced (P<0.05) oxidant-induced, but not mutagen-induced, DNA damage. Neither the phytosterols nor CLA induced apoptosis or modulated COX-2 production. In conclusion, campesterol, beta-sitosterol, beta-sitostanol, c10t12-CLA, and t9t11-CLA were not toxic to Caco-2 cells, at the lower levels tested, and did not exhibit potential anti-carcinogenic activity.
authors.affiliation: Department of Food and Nutritional Sciences, University College Cork, Western Road, Cork, Ireland.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Daly
authors.forename: S Aisling
authors.initials: SA
authors.lastname: Aherne
authors.forename: Tom P
authors.initials: TP
authors.lastname: O'Connor
authors.forename: Nora M
authors.initials: NM
authors.lastname: O'Brien
mesh_terms: D018938:Caco-2 Cells; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000031:analogs & derivatives / Q000494:pharmacology; D020552:Comet Assay; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004249:DNA Damage; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019787:Linoleic Acid / Q000494:pharmacology*; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D010840:Phytosterols / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D012855:Sitosterols / Q000494:pharmacology
chemical_list: D009153:Mutagens; D010840:Phytosterols; D020011:Protective Agents; D012855:Sitosterols; D008769:Methylnitronitrosoguanidine; C021273:campesterol; C025473:gamma-sitosterol; D002784:Cholesterol; D019787:Linoleic Acid; D006861:Hydrogen Peroxide; C021255:stigmastanol; D007770:L-Lactate Dehydrogenase; D051546:Cyclooxygenase 2