TitleTranscriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention.
Publication TypeJournal Article
Year of Publication2014
AuthorsBeaver, LM, Buchanan, A, Sokolowski, EI, Riscoe, AN, Wong, CP, Chang, JH, Löhr, CV, Williams, DE, Dashwood, RH, Ho, E
JournalMol Nutr Food Res
Volume58
Issue10
Pagination2001-13
Date Published2014 Oct
ISSN1613-4133
KeywordsAnticarcinogenic Agents, Carcinogenesis, Cell Line, Tumor, Cells, Cultured, Chemoprevention, Dietary Supplements, Gene Expression Regulation, Neoplastic, Gene Silencing, Humans, Isothiocyanates, Male, Neoplasm Proteins, Prostate, Prostatic Neoplasms, Prostatic Neoplasms, Castration-Resistant, RNA, Small Interfering, Sp1 Transcription Factor, Transcriptome
Abstract

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.

DOI10.1002/mnfr.201400269
Alternate JournalMol Nutr Food Res
PubMed ID25044704
PubMed Central IDPMC4184971
Grant ListR01 GM104977 / GM / NIGMS NIH HHS / United States
CA122959 / CA / NCI NIH HHS / United States
P01 CA090890 / CA / NCI NIH HHS / United States
P30 ES00210 / ES / NIEHS NIH HHS / United States
R01 CA080176 / CA / NCI NIH HHS / United States
R01GM104977 / GM / NIGMS NIH HHS / United States
CA90890 / CA / NCI NIH HHS / United States
R01 CA122906 / CA / NCI NIH HHS / United States
CA80176 / CA / NCI NIH HHS / United States
R29 CA065525 / CA / NCI NIH HHS / United States
R01 CA065525 / CA / NCI NIH HHS / United States
CA122906 / CA / NCI NIH HHS / United States
R01 CA122959 / CA / NCI NIH HHS / United States
CA65525 / CA / NCI NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States