Abstract
P-glycoprotein-mediated drug efflux is one of the major causes of the cancer multidrug resistance (MDR). Inhibition of P-glycoprotein could reverse cancer MDR. Here, we show that schisandrin B, a naturally occurring compound from Schisandra chinensis (Turcz.) Baill, bears strong potency to inhibit P-glycoprotein. Schisandrin B reversed the drug resistance of four MDR cell lines characterized with overexpression of P-glycoprotein and fully restored the intracellular drug accumulation by interacting with P-glycoprotein. Schisandrin B has a core structure of dibenzocyclooctadiene, representing a novel P-glycoprotein inhibitor. To our best knowledge, the role of schisandrin B to inhibit P-glycoprotein has not been reported.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors*
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ATP Binding Cassette Transporter, Subfamily B / chemistry*
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / chemistry
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Affinity Labels / pharmacology
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Azides / pharmacology
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Cell Line, Tumor
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Cell Proliferation
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Cyclooctanes / chemistry
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Daunorubicin / pharmacology
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Dihydropyridines / pharmacology
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Dose-Response Relationship, Drug
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Drug Resistance, Multiple
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Humans
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Inhibitory Concentration 50
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K562 Cells
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Lignans / chemistry*
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Models, Chemical
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Neoplasms / metabolism
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Polycyclic Compounds / chemistry*
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Protein Binding
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Tetrazolium Salts / pharmacology
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Thiazoles / pharmacology
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Time Factors
Substances
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Affinity Labels
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Azides
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Cyclooctanes
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Dihydropyridines
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Lignans
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Polycyclic Compounds
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Tetrazolium Salts
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Thiazoles
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schizandrin B
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azidopine
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thiazolyl blue
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Daunorubicin