The Role of Sulforaphane in the Chemoprevention of Prostate Cancer

Antony Mathew

Prostate cancer is the second most common cancer in men worldwide and the second leading cause of cancer related mortality. The major identified risk factors for development of prostate cancer include age, family history and race. Current treatment regimens lead to mixed results due to many varying risk factors and side effects. This complication in addition to the high rate of over diagnosis with prostate specific antigen (PSA) screening necessitate the need for primary chemoprevention1. Studies have shown that consumption of cruciferous vegetables lowers the risk of prostate cancer. Sulforaphane (SFN) is an isothiocyanate that can be found in cruciferous vegetables such as broccoli, Brussels sprouts and cabbage. It is produced by the hydrolysis of glucoraphanin by myrosinase2. SFN has been known to have chemopreventative properties including the activation of phase II enzymes as measured by quinone reductase activity and inhibition of histone deacetylase (HDAC) evidenced by the increased activity of b-catenin responsive reporter2,3. However, recent studies suggest that SFN holds many other chemopreventive properties. Based on RNA sequencing, SFN was shown to decrease the expression of Sp1 transcription factors which caused a decrease in prostate cancer cell proliferation4. Western blot analysis also showed decreased expression of the chemokine receptor CXCR4 in prostate cancer cells after treatment with SFN5. Using methyl-DNA immunoprecipitation and genome wide DNA methylation array SFN treatment was shown to decrease DNA methyltransferase expression in normal prostate epithelial cells and androgen independent/dependent prostate cancer cells6. Currently, 5a reductase inhibitors are the only class of drugs that have been shown to reduce incidence of prostate cancer in large randomized trials. However, their efficacy as a chemopreventive agent remains uncertain due to high cost and risk of developing high grade prostate cancer7. SFNs low toxicity and multiple mechanisms makes it an attractive potential chemopreventative agent. Further research in clinical settings is needed harness and understand the potential of SFN as a viable chemopreventative agent.

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