title: Coffee induces breast cancer resistance protein expression in Caco-2 cells.
abstract: Coffee is a beverage that is consumed world-wide on a daily basis and is known to induce a series of metabolic and pharmacological effects, especially in the digestive tract. However, little is known concerning the effects of coffee on transporters in the gastrointestinal tract. To elucidate the effect of coffee on intestinal transporters, we investigated its effect on expression of the breast cancer resistance protein (BCRP/ABCG2) in a human colorectal cancer cell line, Caco-2. Coffee induced BCRP gene expression in Caco-2 cells in a coffee-dose dependent manner. Coffee treatment of Caco-2 cells also increased the level of BCRP protein, which corresponded to induction of gene expression, and also increased cellular efflux activity, as judged by Hoechst33342 accumulation. None of the major constituents of coffee tested could induce BCRP gene expression. The constituent of coffee that mediated this induction was extractable with ethyl acetate and was produced during the roasting process. Dehydromethylepoxyquinomicin (DHMEQ), an inhibitor of nuclear factor (NF)-κB, inhibited coffee-mediated induction of BCRP gene expression, suggesting involvement of NF-κB in this induction. Our data suggest that daily consumption of coffee might induce BCRP expression in the gastrointestinal tract and may affect the bioavailability of BCRP substrates.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.
authors.forename: Marina
authors.initials: M
authors.lastname: Isshiki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Tamura
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001549:Benzamides / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D018929:Cell Culture Techniques; D003069:Coffee; D003512:Cyclohexanones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001549:Benzamides; D001562:Benzimidazoles; D003069:Coffee; D003512:Cyclohexanones; D016328:NF-kappa B; D009363:Neoplasm Proteins; D010936:Plant Extracts; C464444:dehydroxymethylepoxyquinomicin; C017807:bisbenzimide ethoxide trihydrochloride