Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 58, Issue 10, Pages 2001-2013Publisher
WILEY-BLACKWELL
DOI: 10.1002/mnfr.201400269
Keywords
Chemoprevention; Prostate cancer; RNA sequencing; Specificity protein 1; Sulforaphane
Categories
Funding
- NIH [CA90890, CA65525, CA122906, CA122959, CA80176, R01GM104977]
- NIEHS Center grant [P30 ES00210]
- Oregon State University
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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.
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