1-methylpropyl-2-imidazolyl-disulfide has been researched along with Prostatic-Neoplasms--Castration-Resistant* in 1 studies
1 other study(ies) available for 1-methylpropyl-2-imidazolyl-disulfide and Prostatic-Neoplasms--Castration-Resistant
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Thioredoxin-1 protects against androgen receptor-induced redox vulnerability in castration-resistant prostate cancer.
Androgen deprivation (AD) therapy failure leads to terminal and incurable castration-resistant prostate cancer (CRPC). We show that the redox-protective protein thioredoxin-1 (TRX1) increases with prostate cancer progression and in androgen-deprived CRPC cells, suggesting that CRPC possesses an enhanced dependency on TRX1. TRX1 inhibition via shRNA or a phase I-approved inhibitor, PX-12 (untested in prostate cancer), impedes the growth of CRPC cells to a greater extent than their androgen-dependent counterparts. TRX1 inhibition elevates reactive oxygen species (ROS), p53 levels and cell death in androgen-deprived CRPC cells. Unexpectedly, TRX1 inhibition also elevates androgen receptor (AR) levels under AD, and AR depletion mitigates both TRX1 inhibition-mediated ROS production and cell death, suggesting that AD-resistant AR expression in CRPC induces redox vulnerability. In vivo TRX1 inhibition via shRNA or PX-12 reverses the castration-resistant phenotype of CRPC cells, significantly inhibiting tumor formation under systemic AD. Thus, TRX1 is an actionable CRPC therapeutic target through its protection against AR-induced redox stress. Topics: Cell Death; Cell Line, Tumor; Cell Proliferation; Cell Survival; Disease Progression; Disulfides; Humans; Imidazoles; Male; Prostatic Neoplasms, Castration-Resistant; Reactive Oxygen Species; Receptors, Androgen; Thioredoxins | 2017 |