Modulation by (iso)flavonoids of the ATPase activity of the multidrug resistance protein

被引:97
作者
Hooijberg, JH [1 ]
Broxterman, HJ [1 ]
Heijn, M [1 ]
Fles, DLA [1 ]
Lankelma, J [1 ]
Pinedo, HM [1 ]
机构
[1] VRIJE UNIV AMSTERDAM,ACAD ZIEKENHUIS,DEPT MED ONCOL,NL-1007 MB AMSTERDAM,NETHERLANDS
关键词
multidrug resistance; multidrug resistance protein; (iso)flavonoids; flavopiridol; dinitrophenyl-S-glutathione; ATPase;
D O I
10.1016/S0014-5793(97)00940-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 1997 Federation of European Biochemical Societies.
引用
收藏
页码:344 / 348
页数:5
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