TY - JOUR AB - Prostate cancer (PCa) cells utilize androgen for their growth. Hence, androgen deprivation therapy (ADT) using anti-androgens, e.g. bicalutamide (BIC) and enzalutamide (ENZ), is a mainstay of treatment. However, the outgrowth of castration resistant PCa (CRPC) cells remains a significant problem. These CRPC cells express androgen receptor (AR) and utilize the intratumoral androgen towards their continued growth and invasion. Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, can decrease AR protein levels. In the present study, we tested the combined efficacy of anti-androgens and SFN in suppressing PCa cell growth, motility and clonogenic ability. Both androgen-dependent (LNCaP) and androgen-independent (C4-2B) cells were used to monitor the effects of BIC and ENZ, alone and in combination with SFN. Co-exposure to SFN significantly (p<0.005) enhanced the anti-proliferative effects of anti-androgens and downregulated expression of the AR-responsive gene, prostate specific antigen (PSA) (p<0.05). Exposure to SFN decreased AR protein levels in a time- and dose-dependent manner with almost no AR detected at 24 h with 15 µM SFN (p<0.005). This rapid and potent AR suppression by SFN occurred by both AR protein degradation, as suggested by cycloheximide (CHX) co-exposure studies, and by suppression of AR gene expression, as evident from quantitative RT-PCR experiments. Pre-exposure to SFN also reduced R1881-stimulated nuclear localization of AR, and combined treatment with SFN and anti-androgens abrogated the mitogenic effects of this AR-agonist (p<0.005). Wound-healing assays revealed that co-exposure to SFN and anti-androgens can significantly (p<0.005) reduce PCa cell migration. In addition, long-term exposures (14 days) to much lower concentrations of these agents, SFN (0.2 µM), BIC (1 µM) and/or ENZ (0.4 µM) significantly (p<0.005) decreased the number of colony forming units (CFUs). These findings clearly suggest that SFN may be used as a promising adjunct agent to augment the efficacy of anti-androgens against aggressive PCa cells. AD - Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA Amity Institute of Biotechnology, Amity University, Noida, U.P. 201313, India AU - Khurana,Namrata AU - Talwar,Sudha AU - Chandra,Partha ,K. AU - Sharma,Pankaj AU - Abdel-Mageed,Asim ,B. AU - Mondal,Debasis AU - Sikka,Suresh ,C. DA - 2016/10/01 DO - 10.3892/ijo.2016.3641 EP - 1619 IS - 4 JO - Int J Oncol KW - prostate cancer androgen receptor sulforaphane bicalutamide enzalutamide combination therapy proliferation migration colony formation PY - 2016 SN - 1019-6439 1791-2423 SP - 1609 ST - Sulforaphane increases the efficacy of anti-androgens by rapidly decreasing androgen receptor levels in prostate cancer cells T2 - International Journal of Oncology TI - Sulforaphane increases the efficacy of anti-androgens by rapidly decreasing androgen receptor levels in prostate cancer cells UR - https://doi.org/10.3892/ijo.2016.3641 VL - 49 ER -