Abstract
The multidrug resistance protein (MRP) is an ATP-dependent transport protein for organic anions, as well as neutral or positively charged anticancer agents. In this study we report that dinitrophenyl-S-glutathione increases ATPase activity in plasma membrane vesicles prepared from the MRP-overexpressing cell line GLC4/ADR. This ATPase stimulation parallels the uptake of DNP-SG in these vesicles. We also show that the (iso)flavonoids genistein, kaempferol and flavopiridol stimulate the ATPase activity of GLC4/ADR membranes, whereas genistin has no effect. The present data are consistent with the hypothesis that certain (iso)flavonoids affect MRP-mediated transport of anticancer drugs by a direct interaction with MRP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters / metabolism*
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Adenosine Triphosphatases / metabolism*
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Carcinoma, Small Cell
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Cell Membrane / enzymology
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Drug Resistance, Multiple / physiology
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Flavonoids / pharmacology
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Genistein
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Glutathione / analogs & derivatives
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Glutathione / metabolism
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Glutathione / pharmacology
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Humans
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Isoflavones / pharmacology*
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Kaempferols*
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Lung Neoplasms
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Multidrug Resistance-Associated Proteins
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Neoplasm Proteins / metabolism*
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Piperidines / pharmacology
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Quercetin / analogs & derivatives
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Quercetin / pharmacology
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Tumor Cells, Cultured
Substances
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ATP-Binding Cassette Transporters
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Flavonoids
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Isoflavones
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Kaempferols
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Multidrug Resistance-Associated Proteins
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Neoplasm Proteins
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Piperidines
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genistin
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S-(2,4-dinitrophenyl)glutathione
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alvocidib
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kaempferol
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Quercetin
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Genistein
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Adenosine Triphosphatases
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Glutathione