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

FEBS Letters

Fles, D.L.A¹  Lankelma, J¹  Pinedo, H.M¹  Hooijberg, J.H¹  Broxterman, H.J¹  Heijn, M¹ 

[1] Academisch Ziekenhuis Vrije Universiteit, Department of Medical Oncology, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands

关键词: Multidrug resistance;    Multidrug resistance protein;    (Iso)flavonoids;    Flavopiridol;    Dinitrophenyl-S-glutathione;    ATPase;    DMSO;    dimethyl sulfoxide;    DNP-SG;    dinitrophenyl-S-glutathione;    GSH;    glutathione;    GSSG;    oxidised glutathione;    MDR;    multidrug resistance;    MOAT;    multiple organic anions transporter;    MRP;    multidrug resistance protein;    Pgp;    P-glycoprotein;   

DOI  :  10.1016/S0014-5793(97)00940-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown