Glyceollin Effects on MRP2 and BCRP in Caco-2 Cells, and Implications for Metabolic and Transport Interactions
| Autor: | Chukwuemezie Chimezie, Melyssa R. Bratton, Robert E. Stratford, Elena Skripnikova, Adina C. Ewing, Elena Y. Glotser, Stephen M. Boue, Pedro Guilherme Souza de Sá, Chandler Schexnayder |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pterocarpans Metabolite Pharmaceutical Science Genistein Biology Pharmacology 030226 pharmacology & pharmacy Article Intestinal absorption 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine ATP Binding Cassette Transporter Subfamily G Member 2 Humans Glyceollin Multidrug resistance-associated protein 2 Biological Transport Transporter Multidrug Resistance-Associated Protein 2 Neoplasm Proteins 030104 developmental biology chemistry Caco-2 Quinolines Efflux Caco-2 Cells Multidrug Resistance-Associated Proteins Propionates Metabolic Networks and Pathways |
| Zdroj: | Journal of Pharmaceutical Sciences. 105:972-981 |
| ISSN: | 0022-3549 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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