Consumption of cruciferous vegetables is associated with a decreased risk of developing prostate cancer. Antineoplastic effects of cruciferous vegetables are attributable to bioactive indoles, most prominently, 3, 3'-diindolylmethane (DIM). In addition to effects on proliferation and apoptosis, DIM acts as an antiandrogen in prostate cancer cell lines. This study characterized the effects of prostatic DIM on the androgen receptor (AR) in patients with prostate cancer. Men with localized prostate cancer were treated with a specially formulated DIM capsule designed for enhanced bioavailability (BR-DIM) at a dose of 225 mg orally twice daily for a minimum of 14 days. DIM levels and AR activity were assessed at the time of prostatectomy. Out of 28 evaluable patients, 26 (93%) had detectable prostatic DIM levels, with a mean concentration of 14.2 ng/gm. The mean DIM plasma level on BR-DIM therapy was 9.0 ng/mL; levels were undetectable at baseline and in follow-up samples. AR localization in the prostate was assessed with immunohistochemistry. After BR-DIM therapy, 96% of patients exhibited exclusion of the AR from the cell nucleus. In contrast, in prostate biopsy samples obtained prior to BR-DIM therapy, no patient exhibited AR nuclear exclusion. Declines in PSA were observed in a majority of patients (71%). Compliance was excellent and toxicity was minimal. In summary, BR-DIM treatment resulted in reliable prostatic DIM levels and anti-androgenic biologic effects at well tolerated doses. These results support further investigation of BR-DIM as a chemopreventive and therapeutic agent in prostate cancer.
American journal of translational research. 2016 Jan 15*** epublish ***
Clara Hwang, Seema Sethi, Lance K Heilbrun, Nilesh S Gupta, Dhananjay A Chitale, Wael A Sakr, Mani Menon, James O Peabody, Daryn W Smith, Fazlul H Sarkar, Elisabeth I Heath
Department of Hematology/Oncology, Josephine Ford Cancer Institute, Henry Ford Health System Detroit, MI, USA., Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, MI, USA., Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, MI, USA., Department of Pathology, Josephine Ford Cancer Institute, Henry Ford Health System Detroit, MI, USA., Department of Pathology, Josephine Ford Cancer Institute, Henry Ford Health System Detroit, MI, USA., Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, MI, USA., Department of Vattikuti Institute of Urology, Josephine Ford Cancer Institute, Henry Ford Health System Detroit, MI, USA., Department of Vattikuti Institute of Urology, Josephine Ford Cancer Institute, Henry Ford Health System Detroit, MI, USA., Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, MI, USA., Department of Pathology, Karmanos Cancer Institute, Wayne State University School of MedicineDetroit, MI, USA; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of MedicineDetroit, MI, USA., Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, MI, USA.