Cancer prevention by phenethyl isothiocyanate (PEITC) in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice [RNA-Seq]

The glucosinolate-derived phenethyl isothiocyanate (PEITC) has been widely reported to reduce the risk of prostate cancer by modulating multiple biologically relevant activities. Emerging evidence suggests that PEITC may exert its anti-cancer effects through epigenetic mechanisms including alterations of DNA methylation. The purpose of this study was to examine the effects of PEITC on prostate carcinogenesis in a murine prostate cancer model (TRAMP). 8 weeks old TRAMP males were fed AIN-93M control diet or diet containing 0.05% PEITC for 8 or16 weeks. We observed reduced tumor incidence in PEITC group (0/5) at 24 weeks of age as compared to control diet group (6/7). We also performed Next-generation sequencing (RNA-seq and SureSelect Methyl-seq) with non-tumor and tumor prostate tissue collected from the above-mentioned TRAMP groups and time matching wildtype (not TRAMP) control diet groups at the same time points. Our bioinformatic analyses reveal that several carcinogenesis pathways as well as pathways of inflammation and cell proliferation were activated in TRAMP group as compared to wildtype group. Surprisingly, these pathways were inhibited by PEITC diet administration. We also identified a number of genes with inverse regulation relationship between their RNA expression and their CpG methylation during prostate carcinogenesis and cancer prevention by PEITC in TRAMP mice. Our study demonstrated that PEITC administration can suppress prostate cancer by epigenetic regulation of key genes. [This GEO/dataset is the RNA-seq part of the study.] mRNA profiles of prostate samples (dorsolateral and ventral) lobes from Wildtype C57BL/6 and TRAMP transgenic mice treated with control AIN93M or PEITC (0.05% w/w) diet.