Modulation by (iso)flavonoids of the ATPase activity of the multidrug resistance protein.
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.
Hooijberg
J H
JH
Academisch Ziekenhuis Vrije Universiteit, Department of Medical Oncology, Amsterdam, The Netherlands.
Broxterman
H J
HJ
Heijn
M
M
Fles
D L
DL
Lankelma
J
J
Pinedo
H M
HM
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D018288:Carcinoma, Small Cell; D002462:Cell Membrane / Q000201:enzymology; D018432:Drug Resistance, Multiple / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D044949:Kaempferols; D008175:Lung Neoplasms; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018528:ATP-Binding Cassette Transporters; D000251:Adenosine Triphosphatases; D005419:Flavonoids; D019833:Genistein; D005978:Glutathione; D007529:Isoflavones; D044949:Kaempferols; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D010880:Piperidines; D011794:Quercetin; C040641:genistin; C030190:S-(2,4-dinitrophenyl)glutathione; C077990:alvocidib; C006552:kaempferol