title: Flavonostilbenes from Sophora alopecuroides L. as multidrug resistance associated protein 1 (MRP1) inhibitors.
abstract: 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.
authors: a State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry , China Pharmaceutical University , 24 Tong Jia Xiang, Nanjing 210009 , People's Republic of China.
authors: Kai
authors: K
authors: Ni
authors: Lei
authors: L
authors: Yang
authors: Chuanxing
authors: C
authors: Wan
authors: Yuanzheng
authors: Y
authors: Xia
authors: Lingyi
authors: L
authors: Kong
mesh_terms: D004317:Doxorubicin / Q000032:analysis / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005452:Fluoresceins / Q000032:analysis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors*; D029909:Sophora / Q000737:chemistry*; D013267:Stilbenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D004317:Doxorubicin; D005419:Flavonoids; D005452:Fluoresceins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013267:Stilbenes; C000595467:alopecurone A; C000595468:alopecurone B; C000595469:alopecurone D; C093616:6-carboxyfluorescein diacetate; C421109:multidrug resistance-associated protein 1
keywords: MRP1; MRP1-transfected U-2 OS; Sophora alopecuroides L; flavonostilbenes; inhibitors; multidrug resistance