Interaction of Isoflavones with the BCRP/ABCG2 Drug Transporter.
Interaction of Isoflavones with the BCRP/ABCG2 Drug Transporter.
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DOI：
10.2174/138920021602150713114921
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发表时间：
2015
影响因子：
2.3
通讯作者：
Aleksunes LM
中科院分区：
文献类型：
--
作者：
Bircsak KM;Aleksunes LM
本文将全面综述膳食异黄酮与atp结合盒（ABC） G2外排转运蛋白（也称为乳腺癌抵抗蛋白（BCRP））之间的相互作用。BCRP在包括肝、肾、肠和胎盘在内的多种器官中表达，介导许多内源性化学物质和外源物的处置和排泄。异黄酮是一类天然存在的化合物，在日常食用的食物和膳食补充剂中含量很高。许多异黄酮，包括染料木素和大豆黄酮及其代谢物，与BCRP相互作用，作为底物、抑制剂和/或基因表达调节剂。迄今为止，各种模型系统已被用于研究异黄酮作为BCRP底物和抑制剂的能力；这些包括全细胞、倒置的质膜囊泡、原位器官灌注以及啮齿动物和绵羊的体内模型。有证据表明，BCRP在介导异黄酮，特别是其共轭形式的处置中起作用。此外，作为抑制剂，这些化合物可能有助于逆转多药耐药和使癌细胞对化疗药物敏感。本综述还将强调异黄酮暴露后BCRP表达和/或功能改变对化学物质的药代动力学和毒性的影响。
This review will provide a comprehensive overview of the interactions between dietary isoflavones and the ATP-binding cassette (ABC) G2 efflux transporter, which is also named the breast cancer resistance protein (BCRP). Expressed in a variety of organs including the liver, kidneys, intestine, and placenta, BCRP mediates the disposition and excretion of numerous endogenous chemicals and xenobiotics. Isoflavones are a class of naturally-occurring compounds that are found at high concentrations in commonly consumed foods and dietary supplements. A number of isoflavones, including genistein and daidzein and their metabolites, interact with BCRP as substrates, inhibitors, and/or modulators of gene expression. To date, a variety of model systems have been employed to study the ability of isoflavones to serve as substrates and inhibitors of BCRP; these include whole cells, inverted plasma membrane vesicles, in situ organ perfusion, as well as in vivo rodent and sheep models. Evidence suggests that BCRP plays a role in mediating the disposition of isoflavones and in particular, their conjugated forms. Furthermore, as inhibitors, these compounds may aid in reversing multidrug resistance and sensitizing cancer cells to chemotherapeutic drugs. This review will also highlight the consequences of altered BCRP expression and/or function on the pharmacokinetics and toxicity of chemicals following isoflavone exposure.