title: Glyceollin Effects on MRP2 and BCRP in Caco-2 Cells, and Implications for Metabolic and Transport Interactions.
abstract: Glyceollins are phytoalexins produced in soybeans under stressful growth conditions. On the basis of prior evaluations, they show potential to treat multiple diseases, including certain cancers, Type 2 diabetes, and cardiovascular conditions. The aim of the present study was to expand on recent studies designed to initially characterize the intestinal disposition of glyceollins. Specifically, studies were undertaken in Caco-2 cells to evaluate glyceollins' effects on apical efflux transporters, namely, MRP2 and BCRP, which are the locus of several intestinal drug-drug and drug-food interactions. 5- (and 6)-carboxy-2',7'-dichloroflourescein (CDF) was used to provide a readout on MRP2 activity, whereas BODIPY-prazosin provided an indication of BCRP alteration. Glyceollins were shown to reverse MRP2-mediated CDF transport asymmetry in a concentration-dependent manner, with activity similar to the MRP2 inhibitor, MK-571. Likewise, they demonstrated concentration-dependent inhibition of BCRP-mediated efflux of BODIPY-prazosin with a potency similar to that of Ko143. Glyceollin did not appreciably alter MRP2 or BCRP expression following 24 h of continuous exposure. The possibility that glyceollin mediated inhibition of genistein metabolite efflux by either transporter was evaluated. However, results demonstrated an interaction at the level of glyceollin inhibition of genistein metabolism rather than inhibition of metabolite transport.
authors: Department of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana 70125.
authors: Chukwuemezie
authors: C
authors: Chimezie
authors: Department of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana 70125.
authors: Adina
authors: A
authors: Ewing
authors: Department of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana 70125.
authors: Chandler
authors: C
authors: Schexnayder
authors: Department of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana 70125.
authors: Melyssa
authors: M
authors: Bratton
authors: Department of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana 70125.
authors: Elena
authors: E
authors: Glotser
authors: Department of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana 70125.
authors: Elena
authors: E
authors: Skripnikova
authors: Universidade Federal do Vale do São Francisco, Petrolina, PE 56403-917, Brazil.
authors: Pedro
authors: P
authors: Sá
authors: Southern Regional Research Center, U.S.D.A., New Orleans, Louisiana 70124.
authors: Stephen
authors: S
authors: Boué
authors: Department of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana 70125. Electronic address: stratfordr@duq.edu.
authors: Robert E
authors: RE
authors: Stratford
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D018938:Caco-2 Cells; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000502:physiology; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D036343:Pterocarpans / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D011422:Propionates; D036343:Pterocarpans; D011804:Quinolines; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C059141:verlukast; C017343:glyceollin
keywords: active transport; drug interaction; efflux pumps; flavonoids; food effects; genistein; glyceollin; intestinal absorption; intestinal metabolism; phytoestrogen