Inhibition effect of cypermethrin mediated by co-regulators SRC-1 and SMRT in interleukin-6-induced androgen receptor activation

Autor: Jin-Peng Zhang, Mei-Rong Zhang, Zhen Ding, Li-Chun Xu, Xiao-Long Zhou, Ji-Long Zhou, Xing Ge, Hui Wang, Qiang Ju, Qiao-Mei Shi, Hong-Min Yu, Chen Pan, Qi Wang
Rok vydání: 2016
Předmět:
Zdroj: Chemosphere. 158:24-29
ISSN: 0045-6535
DOI: 10.1016/j.chemosphere.2016.05.053
Popis: 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.
Databáze: OpenAIRE