Determination of the differential estrogenicity of isoflavonoids by E2-ER-ERE-dependent gene expression in recombinant yeast and MCF-7 human breast cancer cells
Determination of the differential estrogenicity of isoflavonoids by E2-ER-ERE-dependent gene expression in recombinant yeast and MCF-7 human breast cancer cells
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DOI：
10.1016/j.foodchem.2007.11.020
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发表时间：
2008-05-15
期刊：
影响因子：
8.8
通讯作者：
Teng, Shu-Chun
中科院分区：
文献类型：
--
作者：
Lin, Chuan-Chuan;Tsai, Yun-Luen;Teng, Shu-Chun
几十年来，使用含有植物雌激素的天然来源作为替代激素替代疗法(HRT)一直是一个争论的主题。有必要开发鉴定这些植物雌激素的分析方法。本研究以经典回文雌激素反应元件(ERE)-ADE2为报告基因，在酵母筛选系统和MCF-7细胞培养系统中检测了红三叶和大豆中发现的五种异黄酮类化合物，包括生物素A、大豆苷元、芒柄花素、金雀异黄素和黄豆黄素，并比较了ER依赖基因的mRNA水平。在基于酵母的检测中，五种异黄酮类化合物显示出不同程度的雌激素活性。选择雌激素(E-2)调节雌激素受体(ER)的主要基因hTERT、c-myc、bcl2和Ha-ras(致癌)和苯醌还原酶(QR)、人补体3(C3)和COX7RP(非致癌)作为标记基因，以MCF-7细胞为基础进行内源性基因表达分析。结果表明，5种异黄酮类化合物对这些E-2-ER-ERE依赖的标记基因的表达水平有不同的调节作用，导致了不同的表达模式，与E-2的表达模式也有显著差异。此外，还显示了生物素A和芒柄花素对E-2诱导的MCF-7细胞标志基因转录的抗雌激素作用。综上所述，这些结果对于这些天然产生的异黄酮类药物的安全性和有效性具有重要意义。(C)2007爱思唯尔有限公司。保留所有权利。
The use of phytoestrogens-containing natural sources as alternative hormone replacement therapy (HRT) has been a subject of debate for decades. Development of assays to characterize these phytoestrogens is required. In this study, differential estrogenicities of five isoflavonoids found in red clover and soy, including biochanin A, daidzein, formononetin, genistein and glycitein were examined in a yeast-based screen system with a classical palindromic estrogen response element (ERE)-ADE2 reporter and in a MCF-7 cell culture system with mRNA levels of ER-dependent genes compared. In a yeast-based assay, five isoflavonoids showed various extents of estrogenic potencies. A collection of primary estrogen receptor (ER)-regulated genes by estradiol (E-2), including hTERT, c-MYC, BCL2 and Ha-ras (oncogenic) and quinone reductase (QR), human complement 3 (C3) and COX7RP (non-oncogenic) were selected as marker genes for a MCF-7 cell-based endogenous gene expression assay. The results indicated that the mRNA levels of these E-2-ER-ERE-dependent marker genes were regulated differentially by five isoflavonoids, leading to distinct expression patterns, which are also significantly different from that of E-2. Moreover, the anti-estrogenic effects of biochanin A and formononetin on E-2-induced transcriptions of marker genes in MCF-7 cells were also displayed. Taken together, these results are significant for these naturally occurring isoflavonoids regarding the issues of safety and efficacy. (C) 2007 Elsevier Ltd. All rights reserved.