The effect of quercetin phase II metabolism on its MRP1 and MRP2 inhibiting potential
| Autor: | Heleen M. Wortelboer, Jelmer J. van Zanden, Hester van der Woude, Nicole H.P. Cnubben, Judith C.H. Vaessen, Mustafa Usta, Ivonne M.C.M. Rietjens |
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| Přispěvatelé: | TNO Kwaliteit van Leven |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Biomedical Research
Flavonoid Glucuronidation plant animal cell Pharmacology cancer cell culture Toxicology cell-line Biochemistry quercetin chemistry.chemical_compound drug-resistance Multidrug Resistance Protein 1 multidrug-resistance protein p-glycoprotein rat heterocyclic compounds multidrug resistance protein 1 enzyme inhibition multidrug resistance protein 2 P-glycoprotein chemistry.chemical_classification biology Multidrug resistance-associated protein 2 MRP2 article Multidrug Resistance-Associated Protein 2 enzyme activity modulation ABC transporters priority journal MRP1 ABC transporter Multidrug Resistance-Associated Proteins Quercetin Phase II metabolism cancer chemotherapy multidrug resistance Cell Line Tumor Animals Humans flavonoid controlled study human Toxicologie VLAG Flavonoids nonhuman human cell glucuronidation Membrane Transport Proteins Metabolism Rats Calcein dietary flavonoids glycoprotein-mediated transport chemistry biology.protein chemical structure identification abc transporters |
| Zdroj: | Biochemical Pharmacology, 2, 74, 345-351 Biochemical Pharmacology 74 (2007) 2 Biochemical Pharmacology, 74(2), 345-351 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/j.bcp.2007.04.002 |
| Popis: | The present study characterises the effect of phase II metabolism, especially methylation and glucuronidation, of the model flavonoid quercetin on its capacity to inhibit human MRP1 and MRP2 activity in Sf9 inside-out vesicles. The results obtained reveal that 3′-O-methylation does not affect the MRP inhibitory potential of quercetin. However, 4′-O-methylation appeared to reduce the potential to inhibit both MRP1 and MRP2. In contrast, glucuronidation in general, and especially glucuronidation at the 7-hydroxylmoiety, resulting in 7-O-glucuronosyl quercetin, significantly increased the potential of quercetin to inhibit MRP1 and MRP2 mediated calcein transport with inhibition of MRP1 being generally more effective than that of MRP2. Overall, the results of this study reveal that the major phase II metabolites of quercetin are equally potent or even better inhibitors of human MRP1 and MRP2 than quercetin itself. This finding indicates that phase II metabolism of quercetin could enhance the potential use of quercetin- or flavonoids in general-as an inhibitor to overcome MRP-mediated multidrug resistance. © 2007 Elsevier Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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