Sulforaphane and erucin increase MRP1 and MRP2 in human carcinoma cell lines
Sulforaphane and erucin increase MRP1 and MRP2 in human carcinoma cell lines
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DOI：
10.1016/j.jnutbio.2007.02.014
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发表时间：
2008-04-01
影响因子：
5.6
通讯作者：
Jeffery, Elizabeth H.
中科院分区：
文献类型：
--
作者：
Harris, Kristin E.;Jeffery, Elizabeth H.
多药耐药(MDR)转运体被称为第三阶段解毒系统，因为它们不仅输出内源性代谢物，而且通过从组织中主动分泌外来化合物及其代谢物来提供保护，免受外来生物的伤害。然而，肿瘤中MDR的过度表达可能导致耐药性，这是许多癌症治疗的主要障碍，包括肺癌。十字花科蔬菜中的异硫氰酸盐，如萝卜硫素(SF)和芥子蛋白(ER)，已知能增强II相解毒酶的表达。在这里，我们评估了SF和ER调节MDR mRNA和蛋白表达的能力，以及转运蛋白的活性。Western blotting检测ER或SF对肝(HepG2)、结肠(Caco-2)和肺癌(A549)癌细胞P-糖蛋白(P-gp)、多药耐药蛋白1(MRP1)和多药耐药蛋白2(MRP2)的表达。SF和ER均不影响P-gp在所有受试细胞系中的表达。SF和ER均可剂量依赖性地上调HepG2细胞MRP1、MRP2和Caco-2细胞MRP2的蛋白水平。在A549肺癌细胞中，SF使MRP1和MRP2的mRNA和蛋白水平升高；ER引起MRP1和MRP2mRNA的增加，但幅度较小。此外，SF和ER增加了A549细胞中5-羧基荧光素二乙酸酯MRP1依赖的外流，尽管SF的影响明显大于ER。这些发现的含义是，在推荐在化疗中使用之前，应该仔细研究调节解毒系统的饮食成分，因为这些化合物可能会对化疗药物的处置产生额外的影响。(C)2008 Elsevier Inc.保留所有权利。
Multidrug resistance (MDR) transporters have been termed the Phase III detoxification system because they not only export endogenous metabolites but provide protection from xenobiotic insult by actively secreting foreign compounds and their metabolites from tissues. However, MDR overexpression in tumors can lead to drug resistance, a major obstacle in the treatment of many cancers, including lung cancer. Isothiocyanates from cruciferous vegetables, such as sulforaphane (SF) and erucin (ER), are known to enhance the expression of Phase II detoxification enzymes. Here we evaluated the ability of SF and ER to modulate MDR mRNA and protein expressions, as well as transporter activity. The expression of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1) and multidrug resistance protein 2 (MRP2) in liver (HepG2), colon (Caco-2) and lung (A549) cancer cells treated with ER or SF was analyzed by Western blotting. Neither SF nor ER affected P-gp expression in any of the cell lines tested. Both SF and ER increased the protein levels of MRP1 and MRP2 in HepG2 cells and of MRP2 in Caco-2 cells in a dose-dependent manner. In A549 lung cancer cells, SF increased MRP1 and MRP2 mRNA and protein levels; ER caused a similar yet smaller increase in MRP1 and MRP2 mRNA. In addition, SF and ER increased MRP1-dependent efflux of 5-carboxyfluorescein diacetate in A549 cells, although again the effect of SF was substantially greater than that of ER. The implication of these findings is that dietary components that modulate detoxification systems should be studied carefully before being recommended for use during chemotherapy, as these compounds may have additional influences on the disposition of chemotherapeutic drugs. (C) 2008 Elsevier Inc. All rights reserved.