4.7 Article

Schisandrin B: A dual inhibitor of P-glycoprotein and multidrug resistance-associated protein 1

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CANCER LETTERS
卷 246, 期 1-2, 页码 300-307

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ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2006.03.009

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schisandrin B; cancer multidrug resistance; multidrug resistance - associated protein 1; probenecid

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We recently reported that schisandrin B (Sch B) was a novel P-glycoprotein (P-gp) inhibitor. In this study, we revealed that Sch B was also an effective inhibitor of multidrug resistance-associated protein 1 (MRP1). The activities of Sch B to reverse MRP1-mediated drug resistance was tested using HL60/ADR and HL60/MRP, the human promyelocytic leukemia cell lines with the overexpression of MRP1 but not P-gp. Sch B resumed daunorubicin and carboxyfluorescein diacetate (CFDA, a specific substrate for MRP1) accumulation and retention in HL60/ADR cells in a time and concentration dependent manner. At the equimolar concentration, Sch B demonstrated significantly stronger potency than probenecid, a MRP1 inhibitor. This study, together with the previous findings, demonstrated that Sch B was a dual inhibitor of P-gp and MRP1, a type suggested to be preferable to the use of combination of two specific modulators to prevent drug-drug interaction and cumulative toxicities. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

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