Dibenzocyclooctadiene lignans - A class of novel inhibitors of multidrug resistance-associated protein 1
Dibenzocyclooctadiene lignans - A class of novel inhibitors of multidrug resistance-associated protein 1
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DOI：
10.1016/j.lfs.2006.11.002
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发表时间：
2007-01-30
期刊：
影响因子：
6.1
通讯作者：
Hu, Xun
中科院分区：
文献类型：
--
作者：
Li, Ling;Pan, Qiangrong;Hu, Xun
我们最近报道了二苯并环辛木脂素类化合物是一类新的P-糖蛋白（P-gp）抑制剂。在这项研究中，我们证明了这类木脂素也是多药耐药相关蛋白1（MRP 1）的有效抑制剂。以人早幼粒细胞白血病细胞株HL 60/阿霉素（ADR）和HL 60/多药耐药相关蛋白（MRP）为研究对象，检测了五味子甲素（Schisandrin A）、五味子乙素（Schisandrin B）、五味子醚甲素（Schisantherin A）、五味子醇甲（Schisandrol A）和五味子醇乙（Schisandrol B）5种二苯并环辛脂素类化合物对MRP 1介导的耐药的逆转作用。5种木脂素能有效逆转两种细胞株对长春新碱、柔红霉素和VP-16的耐药性。本研究与我们以前的报道一起证明了二苯并环辛木脂素具有多种抗肿瘤多药耐药的活性，包括抑制P-gp和MRP 1，以及促进细胞凋亡。考虑到癌症多药耐药（MDR）是多因素的，具有广泛活性的药物优于使用几种特异性调节剂的组合以防止药物相互作用和累积毒性。(c)2006年爱思唯尔公司All rights reserved.
We recently reported that dibenzocyclooctadiene lignans were a novel class of P-glycoprotein (P-gp) inhibitors. In this study, we demonstrated that the lignans of this class were also effective inhibitors of multidrug resistance-associated protein 1 (MRP1). The activities of 5 dibenzocyclooctadiene lignans (schisandrin A, schisandrin B, schisantherin A, schisandrol A, and schisandrol B) to reverse MRP1-mediated drug resistance were tested using HL60/Adriamycin (ADR) and HL60/Multidrug resistance-associated protein (MRP), two human promyelocytic leukemia cell lines with overexpression of MRP1 but not P-gp. The five lignans could effectively reverse drug resistance of the two cell lines to vincristine, daunorubicin, and VP-16. This study, together with our previous reports, proves that dibenzocyclooctadiene lignans have multiple activities against cancer multidrug resistance, including inhibition of P-gp and MRP1, and enhancement of apoptosis. Considering that cancer multidrug resistance (MDR) is multifactorial, agents with broad activities are preferable to the use of combination of several specific modulators to prevent drug-drug interaction and cumulative toxicity. (c) 2006 Elsevier Inc. All rights reserved.