JS-K, a glutathione/glutathione S-transferase-activated nitric oxide releasing prodrug inhibits androgen receptor and WNT-signaling in prostate cancer cells.

Background: Nitric oxide (NO) and its oxidative reaction products have been repeatedly shown to block steroid receptor function via nitrosation of zinc finger structures in the DNA-binding domain (DBD). In consequence NO-donors could be of special interest for the treatment of deregulated androgen receptor(AR)-signaling in castration resistant prostate cancer (CRPC).

Methods: Prostate cancer (PCa) cells were treated with JS-K, a diazeniumdiolate derivate capable of generating large amounts of intracellular NO following activation by glutathione S-transferase.

AR-Q640X, a model to study the effects of constitutively active C-terminally truncated AR variants in prostate cancer cells.

Purpose: A recently identified mechanism allowing prostate cancer (PCa) cells to grow in the absence of androgens is the expression of constitutively active, C-terminally truncated androgen receptor (AR) variants lacking vast parts of the ligand-binding domain. These AR variants termed ARΔLBD are either products of alternative splicing, point mutations leading to premature stop codons or proteolytic cleavage of the AR. Some controversies exist about the requirement of additional full-length AR for the full transcriptional activity of the ARΔLBD.

Inability of NCoR/SMRT to repress androgen receptor transcriptional activity in prostate cancer cell lines.

The molecular mechanisms leading to castration-resistant prostate cancer (CRPC) are poorly understood. Among several mechanisms leading to CRPC growth a dysregulation of androgen receptor (AR) co-regulators (i.e.