title: Oleic acid decreases BCRP mediated efflux of mitoxantrone in Caco-2 cell monolayers.
abstract: Breast cancer resistance protein (BCRP) efflux restricts intestinal absorption of substances like heterocyclic amines, mycotoxins and certain human and veterinary drugs. Fat rich meals seem to increase absorption of drugs which are BCRP substrates or inhibitors. We therefore hypothesize that absorption of toxicants normally effluxed by BCRP are increased by fatty acids in food. Transport across and accumulation of 3H-Mitoxantrone (MXR) in Caco-2 cell monolayers were measured after 60 min exposure to emulsions of 3H-MXR (1μM) and oleic acid (0.5-5 mM). In addition, BCRP gene expression (RT-PCR) and the amount of BCRP protein (Western blot) were measured in oleic acid exposed Caco-2 cells. Oleic acid increased transport of MXR in a concentration dependent manner and 2 mM oleic acid or higher increased accumulation of MXR in cells, without any signs of cytotoxicity. Gene expression of BCRP was increased after exposure to oleic acid for 6 h, but the amount of BCRP protein was not increased. In conclusion, oleic acid clearly induced BCRP gene expression and reduced BCRP mediated efflux, although the amount of BCRP in cells was not affected. Consequently, effects of fatty acids on BCRP mediated efflux are important to consider in risk assessment of toxicants in food.
authors: Risk and Benefit Assessment Department, National Food Agency, P.O. Box 622, SE-75126 Uppsala, Sweden. bfas@slv.se
authors: Bitte
authors: B
authors: Aspenström-Fagerlund
authors: Jonas
authors: J
authors: Tallkvist
authors: Nils-Gunnar
authors: NG
authors: Ilbäck
authors: Anders W
authors: AW
authors: Glynn
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000042:Absorption; D000970:Antineoplastic Agents / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008942:Mitoxantrone / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D019301:Oleic Acid; D008942:Mitoxantrone