Anti-estrogenic activity of tris(2,3-dibromopropyl) isocyanurate through disruption of co-activator recruitment: experimental and computational studies
文献类型：期刊论文
| 作者 | Liang, Yong1,2; Cao, Huiming1; Li, Xun2,3; Zhang, Wenjuan1; Wang, Ling1; Pan, Yu1; Zhou, Zhen4; Chen, Minjie2; Zhang, Aiqian5; Song, Maoyong5 |
| 刊名 | ARCHIVES OF TOXICOLOGY
 |
| 出版日期 | 2018-04-01 |
| 卷号 | 92期号:4页码:1471-1482 |
| 关键词 | Tris(2,3-dibromopropyl) isocyanurate MVLN assays AF-2 site Molecular dynamics simulations |
| ISSN号 | 0340-5761 |
| DOI | 10.1007/s00204-018-2159-2 |
| 英文摘要 | As a potential endocrine disruptor, tris(2,3-dibromopropyl) isocyanurate (TBC) has previously been demonstrated to reduce expression of estrogen-dependent vitellogenin (vtg) mRNA in adult zebrafish. However, the underlying toxicity pathways and molecular mechanisms involved in TBC-induced endocrine disruption remain elusive. In the current study, E-Screen and MVLN assays were employed to explore the potential anti-estrogenic effects of TBC via the estrogen receptor alpha (ER alpha)-mediated signaling pathway. Within a dose range between 1 x 10(-9) and 1 x 10(-7) M, TBC significantly inhibited 17 beta-estradiol (E-2)-induced cell proliferation in a breast cancer cell line. The luciferase activity induced by E-2 was also significantly inhibited by TBC in a dose-dependent manner. Moreover, neither TBC nor E-2 affected proliferation of the ER alpha-negative breast cancer cell line MDA-MB-231. These experimental results confirmed that TBC has anti-estrogenic effects by affecting the ER alpha-mediated signaling pathway. By comparing TBC with known antagonists of ER alpha, we found that TBC has similar molecular structure as certain co-activator binding inhibitors. Therefore, using molecular docking and molecular dynamics simulations, TBC was further predicted to competitively occupy the surface site of ER alpha rather than the canonical E-2-binding pocket of ER alpha, thus disrupt subsequent co-activator recruitment and transcription activation. Our findings elucidate the anti-estrogenic mechanism of TBC at the atomic level and highlight the biological importance of surface sites of nuclear receptors for a risk assessment of potential environmental pollutants. |
| 资助项目 | Strategic Priority Research Program of the Chinese Academy of Sciences[XDB14030501] ; National Nature Science Foundation of China[21277062] ; National Nature Science Foundation of China[21477049] ; Natural Science Foundation of Hubei Province[2017CFB368] |
| WOS研究方向 | Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000429103700009 |
| 出版者 | SPRINGER HEIDELBERG |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/4944]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Liang, Yong; Song, Maoyong |
| 作者单位 | 1.Jianghan Univ, Inst Environm & Hlth, Wuhan 430056, Hubei, Peoples R China 2.Jianghan Univ, Sch Med, Wuhan 430056, Hubei, Peoples R China 3.Chinese Acad Sci, Wuhan Bot Garden, Key Lab Plant Germplasm Enhancement & Specialty A, Wuhan 430074, Hubei, Peoples R China 4.Jianghan Univ, Minist Educ, Key Lab Optoelect Chem Mat & Devices, Wuhan 430056, Hubei, Peoples R China 5.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, POB 2871, Beijing 100085, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liang, Yong,Cao, Huiming,Li, Xun,et al. Anti-estrogenic activity of tris(2,3-dibromopropyl) isocyanurate through disruption of co-activator recruitment: experimental and computational studies[J]. ARCHIVES OF TOXICOLOGY,2018,92(4):1471-1482. |
| APA | Liang, Yong.,Cao, Huiming.,Li, Xun.,Zhang, Wenjuan.,Wang, Ling.,...&Song, Maoyong.(2018).Anti-estrogenic activity of tris(2,3-dibromopropyl) isocyanurate through disruption of co-activator recruitment: experimental and computational studies.ARCHIVES OF TOXICOLOGY,92(4),1471-1482. |
| MLA | Liang, Yong,et al."Anti-estrogenic activity of tris(2,3-dibromopropyl) isocyanurate through disruption of co-activator recruitment: experimental and computational studies".ARCHIVES OF TOXICOLOGY 92.4(2018):1471-1482. |
入库方式： OAI收割
来源：武汉植物园
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