Hooijberg J H, Broxterman H J, Heijn M, Fles D L, Lankelma J, Pinedo H M
Academisch Ziekenhuis Vrije Universiteit, Department of Medical Oncology, Amsterdam, The Netherlands.
FEBS Lett. 1997 Aug 18;413(2):344-8. doi: 10.1016/s0014-5793(97)00940-x.
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.
