Sulforaphane increases the efficacy of anti-androgens by rapidly decreasing androgen receptor levels in prostate cancer cells

  • Authors:
    • Namrata Khurana
    • Sudha Talwar
    • Partha K. Chandra
    • Pankaj Sharma
    • Asim B. Abdel-Mageed
    • Debasis Mondal
    • Suresh C. Sikka
  • View Affiliations

  • Published online on: August 2, 2016     https://doi.org/10.3892/ijo.2016.3641
  • Pages: 1609-1619
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Abstract

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.
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October-2016
Volume 49 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Khurana N, Talwar S, Chandra PK, Sharma P, Abdel-Mageed AB, Mondal D and Sikka SC: Sulforaphane increases the efficacy of anti-androgens by rapidly decreasing androgen receptor levels in prostate cancer cells. Int J Oncol 49: 1609-1619, 2016
APA
Khurana, N., Talwar, S., Chandra, P.K., Sharma, P., Abdel-Mageed, A.B., Mondal, D., & Sikka, S.C. (2016). Sulforaphane increases the efficacy of anti-androgens by rapidly decreasing androgen receptor levels in prostate cancer cells. International Journal of Oncology, 49, 1609-1619. https://doi.org/10.3892/ijo.2016.3641
MLA
Khurana, N., Talwar, S., Chandra, P. K., Sharma, P., Abdel-Mageed, A. B., Mondal, D., Sikka, S. C."Sulforaphane increases the efficacy of anti-androgens by rapidly decreasing androgen receptor levels in prostate cancer cells". International Journal of Oncology 49.4 (2016): 1609-1619.
Chicago
Khurana, N., Talwar, S., Chandra, P. K., Sharma, P., Abdel-Mageed, A. B., Mondal, D., Sikka, S. C."Sulforaphane increases the efficacy of anti-androgens by rapidly decreasing androgen receptor levels in prostate cancer cells". International Journal of Oncology 49, no. 4 (2016): 1609-1619. https://doi.org/10.3892/ijo.2016.3641