Characterization of diphenyl phthalate as an agonist for estrogen receptor: an in vitro and in silico study
文献类型： 外文期刊
作者： Lv, Chengyu 1 ; Wei, Zhengyi 1 ; Yue, Benjie 2 ; Xia, Ning 3 ; Huang, Wei 1 ; Yue, Yulan 1 ; Li, Zhuolin 1 ; Li, Tiezhu 1 ;
作者机构： 1.Jilin Acad Agr Sci, Inst Agrofood Technol, Changchun 130033, Peoples R China
2.Jilin Agr Univ, Coll Foreign Languages, Changchun, Peoples R China
3.Jilin Agr Univ, Coll Food Sci & Engn, Changchun, Peoples R China
4.Jilin Acad Agr Sci, Off Retirement Affairs, Changchun 130033, Peoples R China
关键词： Phthalate esters; estrogen receptor; endocrine disruption; estrogen activity
期刊名称：TOXICOLOGY MECHANISMS AND METHODS （ 影响因子：2.987； 五年影响因子：2.785 ）
ISSN： 1537-6516
年卷期：
页码：
收录情况： SCI
摘要： Phthalate esters (PAEs) are important pollutants in the environment, which can interfere with the endocrine system by mimicking estrogen. However, limited information is available on modulating the estrogen receptor (ER) of five PAEs including di (2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), benzyl butyl phthalate (BBP), diphenyl phthalate (DPhP) and dicyclohexyl phthalate (DCHP). This study evaluated the agonistic effects of PAEs on human ER. The cytotoxicity assay showed that there were a significant inhibition of the cell proliferation with treatment of five PAEs. Moreover, DPhP does-dependently enhanced ER-mediated transcriptional activity in the reporter gene assay. The increased expression of estrogen-responsive genes (TFF1, CTSD, and GREB1) was also observed in MCF-7 cells treated with DPhP. The result of molecular docking showed that DPhP tended to bind to the agonist conformation of ER compared with the antagonist conformation of ER, demonstrating its agonist characteristic that has been confirmed in the reporter gene assay. Thus, we found that DPhP may be evaluated as an ER agonist in vitro and it can interfere with the normal function of human ER.
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