Potent interaction of flavopiridol with MRP1

J.H. Hooijberg, H.J. Broxterman, G.L. Scheffer, C. Vrasdonk, M. Heijn, M.C. de Jong, R.J. Scheper, J. Lankelma, H.M. Pinedo

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The multidrug resistance protein 1 (MRP1) is an ATP-dependent transport protein for organic anions, as well as neutral or positively charged anticancer agents. In this study we show that flavopiridol, a synthetic flavonoid currently studied in phase 1 trials for its anti-prolifetative characteristics, interacts with MRP1 in a potent way. Flavopiridol, as well as other (iso)flavonoids stimulate the ATPase activity of MRP1 in a dose-dependent way at low micromolar concentrations. A new specific monoclonal antibody against MRP1 (MIB6) inhibits the (iso)flavonoid-induced ATPase activity of plasma membrane vesicles prepared from the MRP1 overexpressing cell line GLC
Original languageEnglish
Pages (from-to)269-276
JournalBritish Journal of Cancer
Publication statusPublished - 1999


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