Investigating the role of oxidative stress control of androgens onto development of prostate cancer

The androgen receptor (AR) is a ligand activated transcription factor that binds DNA response element as a homodimer. The androjen receptor and its signaling pathway play an important role in development, growth and progression of prostate cancer. Oxidative stress caused by an increase in reactive oxygen species levels or a decrease in cellular capacity can evoke the modulation of various cellular events including androgen receptor signaling via direct or indirect interaction. In this study, using prostate cell lines, it is aimed to examine the effect of androgens to related pathways and relationship between oxidative stress formation and prostate cancer. Significance of AR protein loss in inflammation-induced prostate cancer is studied in vitro acute and chronic inflammation models in LNCaP prostate cancer cells. CM treatments resulted in the degradation of AR in dose-dependent manner. İnterestingly, LNAC treatment restored AR. Furthermore, we performed AR silencing together with CM treatment in LNCaP cells, and the results showed that reduced NKX3.1 level was a consequence of the synergetic effects of repression of AR transactivation due to AR depletion and CM-mediated proteasomal degradation. Moreover, the intracellular ROS level was examined using the DCFH assay following the treatment of LNCaP cells with synthetic androgens. Thus, significant reduction in the ROS level was observed. By the evaluation of all data, it is concluded that loss of AR signaling result in the effect on antioxidant response of AR activation.