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Inhibition of estrogen action by 2-phenylchromone as AhR agonist in MCF-7 cells

机译：2-苯基色酮作为AhR激动剂抑制MCF-7细胞中雌激素的作用

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Large amounts of phytoestrogen, a group of estrogen derived from plant sources, are taken from the diet by Asians, but a sign of feminization has not been fully recognized. In this study, we found that some flavonoids inhibited an effect on estrogen action without estrogen receptor (ER) binding. Considering the report that dioxin, an aryl hydrocarbon receptor (AhR) agonist, disrupts the transcriptional activity of ER without binding to the ER, 14 flavonoids were examined for the transcriptional activity of AhR by the yeast reporter assay (AhR). Among them, 2-phenylchromone (flavone, FLA) showed the highest activity. FLA increased the expression of CYP1A1 mRNA, and inhibited the expression of progesterone receptor and pS2 mRNA in MCF-7 cells via non-ER-mediated pathway. Further studies showed that FLA had agonist activity for AhR and enhanced the proteosome-dependent degradation of ER alpha protein. Thus, FLA inhibited the estrogen action without binding to the ER by acting as a competitive agonist for AhR, which meaning that there can be anti-estrogenic flavonoids such as FLA as well as estrogenic ones such as isoflavones. (c) 2007 Elsevier Inc. All rights reserved.
机译：亚洲人从饮食中摄取了大量植物雌激素，这是一组植物来源的雌激素，但女性化的迹象尚未得到充分认识。在这项研究中，我们发现一些类黄酮在没有雌激素受体（ER）结合的情况下抑制了对雌激素作用的作用。考虑到有报道称，二恶英是一种芳基烃受体（AhR）激动剂，可破坏ER的转录活性而不与ER结合，因此通过酵母报道分子分析（AhR）检查了14种类黄酮的AhR转录活性。其中，2-苯基色酮（黄酮，FLA）显示出最高的活性。 FLA通过非ER介导的途径增加MCF-7细胞中CYP1A1 mRNA的表达，并抑制孕激素受体和pS2 mRNA的表达。进一步的研究表明，FLA对AhR具有激动剂活性，并增强了蛋白体依赖的ERα蛋白的降解。因此，FLA通过充当AhR的竞争性激动剂来抑制雌激素作用而不与ER结合，这意味着可以存在抗雌激素类黄酮（例如FLA）和雌激素类黄酮（例如异黄酮）。 （c）2007 Elsevier Inc.保留所有权利。

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