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 H-3-Mitoxantrone (MXR) in Caco-2 cell monolayers were measured after 60 min exposure to emulsions of H-3-MXR (1 mu M) 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. (C) 2012 Elsevier Ltd. All rights reserved.

Keywords

Oleic acid; BCRP; Mitoxantrone; Ko143; Caco-2 cell monolayers

Published in

Food and Chemical Toxicology
2012, volume: 50, number: 10, pages: 3635-3645
Publisher: PERGAMON-ELSEVIER SCIENCE LTD

SLU Authors

• Aspenström-Fagerlund, Bitte

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

• Tallkvist, Jonas

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

Global goals (SDG)

SDG3 Good health and well-being

UKÄ Subject classification

Biochemistry and Molecular Biology

Publication identifier

• DOI: https://doi.org/10.1016/j.fct.2012.07.015

Permanent link to this page (URI)

https://res.slu.se/id/publ/45072