{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T07:02:08Z","timestamp":1775372528707,"version":"3.50.1"},"reference-count":42,"publisher":"American Association for Cancer Research (AACR)","issue":"20","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Despite the initial efficacy of androgen deprivation therapy, most patients with advanced prostate cancer eventually progress to hormone-refractory prostate cancer, for which there is no curative therapy. Previous studies from our laboratory and others have shown the antiproliferative and proapoptotic effects of 3,3\u2032-diindolylmethane (DIM) in prostate cancer cells. However, the molecular mechanism of action of DIM has not been investigated in androgen receptor (AR)\u2013positive hormone-responsive and -nonresponsive prostate cancer cells. Therefore, we investigated the effects of B-DIM, a formulated DIM with greater bioavailability, on AR, Akt, and nuclear factor \u03baB (NF-\u03baB) signaling in hormone-sensitive LNCaP (AR+) and hormone-insensitive C4-2B (AR+) prostate cancer cells. We found that B-DIM significantly inhibited cell proliferation and induced apoptosis in both cell lines. By Akt gene transfection, reverse transcription-PCR, Western blot analysis, and electrophoretic mobility shift assay, we found a potential crosstalk between Akt, NF-\u03baB, and AR. Importantly, B-DIM significantly inhibited Akt activation, NF-\u03baB DNA binding activity, AR phosphorylation, and the expressions of AR and prostate-specific antigen, suggesting that B-DIM could interrupt the crosstalk. Confocal studies revealed that B-DIM inhibited AR nuclear translocation, leading to the down-regulation of AR target genes. Moreover, B-DIM significantly inhibited C4-2B cell growth in a severe combined immunodeficiency\u2013human model of experimental prostate cancer bone metastasis. These results suggest that B-DIM-induced cell proliferation inhibition and apoptosis induction are partly mediated through the down-regulation of AR, Akt, and NF-\u03baB signaling. These observations provide a rationale for devising novel therapeutic approaches for the treatment of hormone-sensitive, but more importantly, hormone-refractory prostate cancer by using B-DIM alone or in combination with other therapeutics. (Cancer Res 2006; 66(20): 10064-72)<\/jats:p>","DOI":"10.1158\/0008-5472.can-06-2011","type":"journal-article","created":{"date-parts":[[2006,10,18]],"date-time":"2006-10-18T09:42:10Z","timestamp":1161164530000},"page":"10064-10072","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Down-regulation of Androgen Receptor by 3,3\u2032-Diindolylmethane Contributes to Inhibition of Cell Proliferation and Induction of Apoptosis in Both Hormone-Sensitive LNCaP and Insensitive C4-2B Prostate Cancer Cells"],"prefix":"10.1158","volume":"66","author":[{"given":"Mohammad M.R.","family":"Bhuiyan","sequence":"first","affiliation":[{"name":"1Pathology and Departments of"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiwei","family":"Li","sequence":"additional","affiliation":[{"name":"1Pathology and Departments of"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjeev","family":"Banerjee","sequence":"additional","affiliation":[{"name":"1Pathology and Departments of"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fakhara","family":"Ahmed","sequence":"additional","affiliation":[{"name":"1Pathology and Departments of"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"1Pathology and Departments of"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shadan","family":"Ali","sequence":"additional","affiliation":[{"name":"2Internal Medicine, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fazlul H.","family":"Sarkar","sequence":"additional","affiliation":[{"name":"1Pathology and Departments of"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","published-online":{"date-parts":[[2006,10,17]]},"reference":[{"key":"2022061622150535400_B1","doi-asserted-by":"crossref","unstructured":"Jemal A, Siegel R, Ward E, et al. 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