Print Email Facebook Twitter The effect of quercetin phase II metabolism on its MRP1 and MRP2 inhibiting potential Title The effect of quercetin phase II metabolism on its MRP1 and MRP2 inhibiting potential Author van Zanden, J.J. van der Woude, H. Vaessen, J. Usta, M. Wortelboer, H.M. Cnubben, N.H.P. Rietjens, I.M.C.M. TNO Kwaliteit van Leven Publication year 2007 Abstract 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. Subject Biomedical ResearchABC transportersFlavonoidsMRP1MRP2Phase II metabolismQuercetinABC transporterflavonoidmultidrug resistance protein 1multidrug resistance protein 2quercetinanimal cellarticlecancer cell culturecancer chemotherapychemical structurecontrolled studyenzyme activityenzyme inhibitionglucuronidationhumanhuman cellmultidrug resistancenonhumanpriority journalratAnimalsCell Line, TumorHumansMembrane Transport ProteinsMultidrug Resistance-Associated ProteinsQuercetinRats To reference this document use: http://resolver.tudelft.nl/uuid:43dacbd3-1cbf-435c-b73c-8af27ee746a7 DOI https://doi.org/10.1016/j.bcp.2007.04.002 TNO identifier 240089 ISSN 0006-2952 Source Biochemical Pharmacology, 74 (2), 345-351 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.