# The Impact of Sulforapahane on Sex-Specific Conditions and Hormone Balance: A Comprehensive Review
## 5 Male Health
### Prostate Cancer and Benign Prostate Hyperplasia (BPH)  
The connection between Brassica vegetable consumption and both prostate and bladder health in men has long been a subject of epidemiologic research. Among the most notable was a review of the epidemiologic evidence from [PERSON] and [PERSON] [3]. An early study of fruit and vegetable consumption in almost 48,000 men identified only those who reported diets containing the cruciferous vegetables broccoli and cabbage as having a protective effect against bladder cancer [124]. Much research has been in vitro, because animal models of prostate cancer were not available during the earliest years of prostate cancer research. Some of the earliest in vitro work on the effects of SF on the prostate focused on epigenetics. These studies identified a dose-dependent inhibition of histone deacetylation (HDAC) in both prostate cancer cells and benign prostate hyperplasia (BPH) cells [125,126]. SF was later shown to destabilize the androgen receptor in prostate cells by inactivating HDAC6 [127]. Dozens of subsequent studies have examined the inhibition of HDAC using small molecules, including sulforaphane (reviewed by [PERSON] [128]). Investigation of the role of SF in inhibiting or preventing prostate cancer has continued to this day, with citations too numerous to recount in this review. Many of those investigations have been solidly mechanism-based and are reviewed more critically by numerous other investigators (e.g., [129, 130, 131]); here, we highlight a few of the more compelling:  
SF attenuated the expression of prostate cancer-associated long noncoding RNAs (lncRNA) using an lncRNA that is overexpressed in prostate cancer and which, upon knockdown, results in decreased proliferation of prostate cancer cells [132]. SF downregulated: (a) galectin-1 (a protein that binds carbohydrates, with wide ranging biological functions) [133] and (b) phosphoglucomutase-3, which mediates both glycogen formation and utilization [134] and impacts the expression of the androgen receptor-responsive gene, prostate specific antigen (PSA), enhancing the efficiency of the pharmaceutical anti-androgens bicaltamide and enzalutamide, two mainstays of androgen deprivation therapy [135]. SF reversed: (a) many of the cancer-associated promoter methylation alterations, including aberrantly methylated genes that are dysregulated or are highly involved in cancer progression [136]; (b) the formation of lysosomal-associated membrane protein 2 (LAMP2), which assists in transporting materials into lysosomes and is involved in autophagy [137]; (c) the formation of specificity protein 1 (Sp1), a transcription factor regulating gene expression including those involved in cell growth, differentiation, and immune response [138]; (d) the Warburg phenomenon, which is a hallmark of cancer in which cancer cells use glycolysis to generate energy, even when oxygen is abundant, thus fermenting most of the glucose they consume into lactate, rather than oxidizing it via respiration [139]. SF increased tissue invasion, a cell culture predictor of metastatic capacity, by regulating E-cadherin and CD44 [140]. SF inhibited: (a) the growth of prostate cancer by down-regulating miRNAs, the noncoding RNAs that induce target genes' mRNA degradation or inhibit the initiation of translation and protein synthesis, as well as the expression of the oncogenic gene DJ-1 [141]; (b) the synthesis of a variety of essential proteins in prostate cancer cells [142]; (c) fatty acid metabolism [143]; (d) autophagy [144], and was synergistic with chloroquine in doing so [145]; (e) c-Myc-mediated traits [146]; (f) activation of the essential-to-life protein STAT3, which is essential to viability [137; 147]; (g) prostate cancer cell migration [144]. SF activated Notch signaling, which is frequently constitutively activated in many human cancers, including prostate. But this activation was not coupled with the effect of SF in inhibiting cell migration and is thus viewed as a therapeutic advantage [148].