Effect of Flavonoids on MRP1-Mediated Transport in Panc-1 Cells
Journal of Pharmaceutical SciencesPublished 17 January 2003
Hang Thi Thu Nguyen, Shuzhong Zhang, Marilyn E. Morris
Citations129
SJR quartileQ1
SJR score0.74
SNIP0.99
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TL;DR
Results indicate that the flavonoids morin, chalcone, silymarin, phloretin, genistein, quercetin, biochanin A, and kaempferol can inhibit MRP1-mediated drug transport, effects that may involve binding interactions with MRp1, as well as modulation of GSH concentrations.
Abstract
The purpose of this study was to identify the effects of dietary flavonoids, which are present in fruits, vegetables, and plant-derived beverages, on the transport of daunomycin (DNM) and vinblastine (VBL) in Panc-1 cells. Panc-1 is a human pancreatic adenocarcinoma cell line, which expresses Multidrug Resistance-Associated Protein1 (MRP1). The 2-h accumulation of (3)H-DNM and (3)H-VBL was determined in the presence and absence of 22 flavonoids. Biochanin-A, genistein, quercetin, chalcone, silymarin, phloretin, morin, and kaempferol, at 100 microM concentrations, all significantly increased the accumulation of both DNM and VBL in Panc-1 cells, with morin increasing DNM and VBL accumulation by 546 +/- 50% (mean +/- SE, n = 9) and 553 +/- 37% (n = 9), respectively. Fisetin treatment significantly decreased the accumulation of both DNM and VBL. Concentration-dependent studies demonstrated significant effects on VBL accumulation at 50 microM, but not at 10 microM concentrations, except for chalcone that was effective at a 10 microM concentration. Following a 24-h incubation, there were no changes in MRP1 membrane expression or glutathione-S-transferase activity in cells. Cellular glutathione (GSH) concentrations were significantly decreased following a 2-h incubation with biochanin A, chalcone, genistein, phloretin, quercetin, and silymarin, and following a 24-h incubation with biochanin A, chalcone, genistein, and phloretin. These results therefore indicate that the flavonoids morin, chalcone, silymarin, phloretin, genistein, quercetin, biochanin A, and kaempferol can inhibit MRP1-mediated drug transport, effects that may involve binding interactions with MRP1, as well as modulation of GSH concentrations.
Keywords
MedicineBiochemistry, Genetics and Molecular BiologyPharmacology, Toxicology and Pharmaceutics
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