Subjective and Objective Effects of Androgen Ablation Therapy on Voice

Saltürk, Zıya; Çakır, Ozan; Kumral, Tolgar Lütfı; Yıldırım, Güven; Ötünçtemur, Alper; Aydoğdu, İmran; Uyar, Yavuz

doi:10.1016/j.jvoice.2014.09.010

Cited by 3 publications

(1 citation statement)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, these clinically approved drugs are administered as first line anti-hormonal therapy in PCa patients. However, the side-effects associated with chronic high doses of these antiandrogens (16)(17)(18) warrant the need to use adjuvant agents that can increase the efficacy of BIC and ENZ, which will significantly reduce their side-effects and augment their clinical effectiveness.…”

Section: Introductionmentioning

confidence: 99%

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

Khurana

Talwar

Chandra

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%