MODULATION BY (ISO)FLAVONOIDS OF THE ATPASE ACTIVITY OF THE MULTIDRUG-RESISTANCE PROTEIN

The multidrug resistance protein (MRP) is an ATP-dependent transport p rotein for organic anions, as well as neutral or positively charged an ticancer agents. In this study we report that dinitrophenyl-S-glutathi one increases ATPase activity in plasma membrane vesicles prepared fro m the MRP-overexpressing cell line GLC4/ADR. This ATPase stimulation p arallels 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 dir ect interaction with MRP. (C) 1997 Federation of European Biochemical Societies.