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

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.