{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T14:25:13Z","timestamp":1778077513260,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2010,3,5]],"date-time":"2010-03-05T00:00:00Z","timestamp":1267747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"crossref","award":["DAMD W81XWH-06-1-0225"],"award-info":[{"award-number":["DAMD W81XWH-06-1-0225"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Walther Cancer Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>To characterize the molecular changes associated with DMAPT\u2010induced prostate cancer cell death and its in vivo activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>CWR22Rv1 and PC\u20103 were subjected to flow cytometry, electrophoretic mobility shift assays, and Western blot studies to measure DMAPT's ability to generate reactive oxygen species (ROS), inhibit NF\u03baB DNA binding, and cause changes in anti\u2010apoptotic proteins. <jats:italic>N<\/jats:italic>\u2010acetyl cysteine (NAC) and short hairpin RNA (shRNA) were used to determine the contribution of ROS and JNK2 activation, respectively. The BrdU incorporation assay was used to measure proliferation and trypan blue studies assessed cell viability after DMAPT treatment. The in vivo activity of DMAPT as a single agent and in combination with bicalutamide or docetaxel was assessed in a subcutaneous xenograft model with athymic nude female mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>DMAPT generated ROS with subsequent JNK activation and inhibited NF\u03baB DNA binding and expression of NF\u03baB\u2010regulated anti\u2010apoptotic proteins. DMAPT increased necrotic and apoptotic cell death in a cell\u2010type\u2010dependent manner and both types of cell death were blocked by NAC. Additionally, shRNA JNK2 partially blocked the anti\u2010proliferative activity of DMAPT. DMAPT inhibited CWR22Rv1 and PC\u20103 cellular proliferation by 100% with 10 and 20\u2009\u00b5M respectively and in vivo, DMAPT was more effective at inhibiting growth than biclutamide (CWR22v1) and docetaxel (PC\u20103).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>DMAPT promotes cell death by both generating ROS and inhibition of NF\u03baB. Its in vivo activity supports the conduct of clinical trials in patients with castrate\u2010resistant disease. 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