Schisandrin B--a novel inhibitor of P-glycoprotein.
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.
Qiangrong
Pan
P
The Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, People's Republic of China.
Wang
Tao
T
Lu
Qinghua
Q
Hu
Xun
X
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry; D000345:Affinity Labels / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D034242:Cyclooctanes / Q000737:chemistry; D003630:Daunorubicin / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D017705:Lignans / Q000737:chemistry*; D008956:Models, Chemical; D009369:Neoplasms / Q000378:metabolism; D011083:Polycyclic Compounds / Q000737:chemistry*; D011485:Protein Binding; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels; D001386:Azides; D034242:Cyclooctanes; D004095:Dihydropyridines; D017705:Lignans; D011083:Polycyclic Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; C015499:schizandrin B; C041130:azidopine; C022616:thiazolyl blue; D003630:Daunorubicin