Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-1-17
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-3549
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:250-257, 2003
pubmed:issnType
Print
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
250-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Effect of flavonoids on MRP1-mediated transport in Panc-1 cells.
pubmed:affiliation
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, 517 Hochstetter Hall, Amherst, New York 14260-1200, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't