title: Inhibition effect of cypermethrin mediated by co-regulators SRC-1 and SMRT in interleukin-6-induced androgen receptor activation.
abstract: It is hypothesized that the pesticide cypermethrin may induce androgen receptor (AR) antagonism via ligand-independent mechanisms. The Real-Time Cell Analysis (RTCA) iCELLigence system was used to investigate the inhibitory effect of cypermethrin on interleukin-6 (IL-6)-induced ligand-independent LNCaP cell growth. Then, the mammalian two-hybrid assays were applied to clarify whether the mechanism of IL-6-induced AR antagonism of cypermethrin was associated with the interactions of the AR and co-activator steroid receptor co-activator-1 (SRC-1) and co-repressor silencing mediator for retinoid and thyroid hormone receptors (SMRT). Cypermethrin inhibited the LNCaP cell growth induced by IL-6. The interactions of AR-SRC-1 and AR-SMRT mediated by IL-6 were suppressed by cypermethrin. The results indicate that the IL-6-mediated AR antagonism induced by cypermethrin is related to repress the recruitment of co-regulators SRC-1 and SMRT to the AR in a ligand-independent manner. Inhibition of the interactions of AR-SRC-1 and AR-SMRT mediated by IL-6 contributes to the AR antagonism induced by cypermethrin.
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Zhou
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ju
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ding
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Zhou
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Ge
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Qiao-Mei
authors.initials: QM
authors.lastname: Shi
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Pan
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Jin-Peng
authors.initials: JP
authors.lastname: Zhang
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Zhang
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Yu
authors.affiliation: School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China. Electronic address: lichunxu2002@163.com.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Xu
mesh_terms: D059002:Androgen Receptor Antagonists / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D056985:Nuclear Receptor Co-Repressor 2 / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1 / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism; D011722:Pyrethrins / Q000737:chemistry*; D011944:Receptors, Androgen / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: C410798:AR protein, human; D059002:Androgen Receptor Antagonists; C508600:IL6 protein, human; D015850:Interleukin-6; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D011722:Pyrethrins; D011944:Receptors, Androgen; C017160:cypermethrin; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1
keywords: Androgen receptor; Anti-androgen; Cypermethrin; Interleukin-6; Silencing mediator for retinoid and thyroid hormone receptors; Steroid receptor co-activator-1