Transcriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention.
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SCOPE: Epidemiological studies provide evidence that consumption of cruciferous vegetables, like broccoli, can reduce the risk of cancer development. Sulforaphane (SFN) is a phytochemical derived from cruciferous vegetables that induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for this cancer-specific cytotoxicity remain unclear. METHODS AND RESULTS: We utilized RNA sequencing and determined the transcriptomes of normal prostate epithelial cells, androgen-dependent prostate cancer cells, and androgen-independent prostate cancer cells treated with SFN. SFN treatment dynamically altered gene expression and resulted in distinct transcriptome profiles depending on prostate cell line. SFN also down-regulated the expression of genes that were up-regulated in prostate cancer cells. Network analysis of genes altered by SFN treatment revealed that the transcription factor Specificity protein 1 (Sp1) was present in an average of 90.5% of networks. Sp1 protein was significantly decreased by SFN treatment in prostate cancer cells and Sp1 may be an important mediator of SFN-induced changes in expression. CONCLUSION: Overall, the data show that SFN alters gene expression differentially in normal and cancer cells with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent.
Beaver, L. M., Buchanan, A., Sokolowski, E. I., Riscoe, A. N., Wong, C. P., Chang, J. H., ... Ho, E.
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Beaver, Laura M||Buchanan, Alex||Sokolowski, Elizabeth I||Riscoe, Allison N||Wong, Carmen P||Chang, Jeff H||Löhr, Christiane V||Williams, David E||Dashwood, Roderick H||Ho, Emily
