Genome‐wide transcriptome analysis of the effects of sulforphane on normal and prostate cancer cells

Abstract

Sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, induces anti‐proliferative and pro‐apoptotic responses in prostate cancer cells, but not normal prostate cells. The mechanisms responsible for these specific chemopreventive properties remain unclear. We utilized RNA sequencing (RNA‐seq) to test the hypothesis that SFN modifies patterns of gene expression that are critical in prostate cancer progression. Normal prostate epithelial cells and prostate cancer cells were treated with 15 uM SFN and the transcriptome was determined at 6 and 24h time points. SFN alters the mRNA expression levels of ~3,000 genes in each sample and the transcriptional response is highly dynamic over time. SFN treatment also alters the expression of non‐coding RNAs including lincRNAs. SFN targets multiple pathways in normal and prostate cancer cells that are critical in cancer including proliferation, apoptosis, angiogenesis, DNA damage response, and cell migration. Network analysis suggests that the transcription factor Sp1 may be a major mediator by which SFN treatment induces changes in gene expression. Studies evaluating the effect of SFN on Sp1 are ongoing and Sp1 mRNA levels are significantly decreased by SFN treatment. Together, this information can be leveraged to help develop intervention strategies to significantly reduce the incidence and severity of prostate cancer. Funding: P01CA090890Grant Funding Source: National Institute of Health