The sulfated conjugate of biochanin A is a substrate of breast cancer resistant protein (ABCG2)
The sulfated conjugate of biochanin A is a substrate of breast cancer resistant protein (ABCG2)
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DOI：
10.1002/bdd.772
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发表时间：
2011-11-01
影响因子：
2.1
通讯作者：
Morris, Marilyn E.
中科院分区：
文献类型：
--
作者：
An, Guohua;Morris, Marilyn E.
(T)he目的探讨乳腺癌耐药蛋白（BCRP，ABCG 2）在鹰嘴豆芽素A及其代谢产物转运中的作用。在MDCK/bcrp 1以及对照细胞中进行转运研究，并使用LC/MS/MS分析样品中鹰嘴豆芽素A糖苷配基和代谢产物。在双向转运研究中，在加入鹰嘴豆芽素A后，在顶室和基底侧室中均检测到鹰嘴豆芽素A硫酸盐。通过RT-PCR分析显示，酶磺基转移酶1A 1在Madin-Darby犬肾（MDCK）-II细胞中表达。在MDCK/Mock细胞中，鹰嘴豆芽素A硫酸盐在其细胞内形成后优先运输到基底外侧，而在MDCK/Bcrp 1细胞中鹰嘴豆芽素A硫酸盐的顶端运输占主导地位。染料木黄酮，一个额外的代谢产物的鹰嘴豆芽素A细胞内形成，也被发现是bcrp 1底物。MDCK/MRP 2（ABCC 2）细胞的研究表明，染料木黄酮和鹰嘴豆芽素A硫酸盐都不是MRP 2底物。相反，鹰嘴豆芽素A糖苷配基不被鼠或人BCRP转运;也不是MRP 2或P-糖蛋白的底物。因此，BCRP可能在鹰嘴豆芽素A硫酸盐的肠循环中发挥重要作用，并通过该机制改变其非底物母体化合物鹰嘴豆芽素A的生物利用度。此外，MDCK-II细胞可能是一个合适的模型，研究协同作用的磺基转移酶与外排转运蛋白。版权所有（C）2011约翰威利父子有限公司
(T)he aim of the study was to investigate the role of breast cancer resistance protein (BCRP, ABCG2) in the transport of biochanin A and its metabolites. Transport studies were carried out in MDCK/bcrp1 as well as in control cells, and samples were analysed for biochanin A aglycone and metabolites using LC/MS/MS. In bidirectional transport studies biochanin A sulfate was detected in both apical and basolateral chambers after the addition of biochanin A. Analysis by RT-PCR revealed that the enzyme sulfotransferase 1A1 is expressed in Madin-Darby canine kidney (MDCK)-II cells. After its intracellular formation, biochanin A sulfate was preferentially transported to the basolateral side in MDCK/Mock cells, whereas apical transport of biochanin A sulfate was predominant in MDCK/Bcrp1 cells. Genistein, an additional metabolite of biochanin A formed intracellularly, was also found to be a bcrp1 substrate. Studies with MDCK/MRP2 (ABCC2) cells demonstrated that both genistein and biochanin A sulfate are not MRP2 substrates. In contrast, biochanin A aglycone was not transported by murine or human BCRP; nor is it a substrate of MRP2 or P-glycoprotein. Therefore, BCRP may play an important role in the enteric cycling of biochanin A sulfate and through this mechanism may alter the bioavailability of its non-substrate parent compound biochanin A. Moreover, MDCK-II cells might be a suitable model to investigate the synergistic role of sulfotransferase enzymes with efflux transporters. Copyright (C) 2011 John Wiley & Sons, Ltd.