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首页> 外文期刊>The Journal of Nutritional Biochemistry >Retinol inhibits aromatase activity and expression in vitro.
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Retinol inhibits aromatase activity and expression in vitro.

机译：视黄醇在体外抑制芳香化酶活性和表达。

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摘要

Aromatase converts androgens into estrogens and is thought to supply a local source of estrogen that facilitates the growth of hormone-responsive tumor cells. Inhibition of aromatase is therefore an important chemopreventive strategy. We investigated the effect of retinol and selected retinoids on the activity and expression of aromatase in two human carcinoma cell lines in vitro. Retinol (ROH) and all-trans retinoic acid (ATRA) significantly inhibited aromatase activity in a concentration-dependent manner in microsomes isolated from JEG-3 human placental carcinoma cells, whereas 9-cis and 13-cis retinoic acid had significant inhibitory activity only at the highest concentrations tested. Similar results were observed in an assay of cellular aromatase activity in MCF-7 human breast cancer cells. Enzyme kinetic studies by double-reciprocal plot demonstrated that ROH inhibited microsomal aromatase activity in a mixed manner. In addition, ROH suppressed both the basal and cAMP-induced expression of aromatase mRNA in MCF-7 cells and inhibited transcription controlled by a cAMP-responsive element. These results suggest that aromatase activity and expression are a molecular target of ROH and chemopreventive retinoids, an activity that may underlie, in part, their inhibitory effects on hormone-dependent cancer. Copyright Copyright 2011 Elsevier Inc. All rights reserved.
机译：芳香酶将雄激素转化为雌激素，并被认为提供了促进激素反应性肿瘤细胞生长的雌激素的局部来源。因此，抑制芳香化酶是重要的化学预防策略。我们调查了视黄醇和选定的类视黄醇对两种人癌细胞系中芳香酶活性和表达的影响。视黄醇（ROH）和全反式视黄酸（ATRA）在从JEG-3人胎盘癌细胞分离的微粒体中以浓度依赖性方式显着抑制芳香化酶活性，而9-顺式和13-顺式视黄酸仅具有显着的抑制活性。在测试的最高浓度下。在MCF-7人乳腺癌细胞中的细胞芳香酶活性测定中观察到了相似的结果。通过双倒数图进行的酶动力学研究表明，ROH以混合方式抑制微粒体芳香酶的活性。此外，ROH抑制了MCF-7细胞中芳香酶mRNA的基础表达和cAMP诱导表达，并抑制了cAMP响应元件控制的转录。这些结果表明，芳香化酶活性和表达是ROH和化学预防性类维生素A的分子靶标，该活性可能部分地是其对激素依赖性癌症的抑制作用。版权版权所有2011 Elsevier Inc.保留所有权利。

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