Flavonoids have always attracted much attention due to their reversal activity on multidrug resistance (MDR). Eight flavonoids isolated from traditional Chinese medicine Sophora alopecuroides L. were applied to test their effect on MDR associated protein 1 (MRP1) through the established predicting assay. Three flavonostilbenes (alopecurone A, B and D) were first found exhibiting potent inhibitory activity on MRP1. All of them dramatically increased 6-carboxyfluorescein diacetate and doxorubicin accumulation in MRP1-transfected U-2 OS cells. The compounds significantly increased the cytotoxicity and decreased the IC₅₀ value of doxorubicin on the MDR cells (12-, 5- and 8-fold, respectively) at a non-toxic concentration (20 μM). Besides, Q-PCR analysis reveals that the MRP1 mRNA level in U-2 OS/MRP1 was also markedly decreased by the three compounds. These findings indicate a new therapeutic role of the herb. The three flavonostilbenes may have the possibility for further development as novel therapeutic reversal agents against MDR.
Keywords: MRP1; MRP1-transfected U-2 OS; Sophora alopecuroides L; flavonostilbenes; inhibitors; multidrug resistance.