Identification of dicyclohexyl phthalate as a glucocorticoid receptor antagonist by molecular docking and multiple in vitro methods

文献类型： 外文期刊

第一作者： Leng, Yue

作者： Leng, Yue;Sun, Yonghai;Li, Tiezhu;Huang, Wei;Lv, Chengyu;Cui, Jingyan;Li, Tiezhu;Wang, Yongjun

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关键词： Phthalates; Nuclear receptors; Endocrine disruption; Anti-glucocorticoid activity

期刊名称：MOLECULAR BIOLOGY REPORTS （ 影响因子：1.402； 五年影响因子：1.703 ）

ISSN： 0301-4851

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收录情况： SCI

摘要： The potential activities of phthalate esters (PAEs) that interfere with the endocrine system have been focused recently. However, information on modulating the glucocorticoid receptor (GR) of PAEs is scarce. Our aim was to evaluate the agonistic / antagonistic properties of PAEs on human GR. Luciferase reporter gene assay revealed that the tested chemicals displayed no agonistic effects but dicyclohexyl phthalate (DCHP) exerted antagonistic activity in a dose-responsive manner for GR in HeLa cells. The effects of DCHP on dexamethasone (DEX)-induced GR nuclear translocation and gene expression of glucocorticoid-responsive gene expression (G6Pase, PEPCK, FAS, GILZ and MKP-1), as well as protein expression of G6Pase and PEPCK were further examined by RT-qPCR and western blot analysis. DCHP antagonized DEX-induced GR nuclear translocation and suppressed gene expression in both mRNA and protein levels. Furthermore, the results of molecular docking and molecular dynamics simulation showed that DCHP could bind to GR and exhibited potential regulation on this target protein. Collectively, we demonstrate that DCHP may act as a GR antagonist in vitro and is considered to exert endocrine effects via human GR.

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