Similar Datasets
Project description: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.]
2023-01-01 | GSE140310 | GEO
Project description: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 bisulfite methyl-seq part of the study.]
2023-01-01 | GSE140311 | GEO
Project description:Cancer prevention by phenethyl isothiocyanate (PEITC) in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice
| PRJNA589278 | ENA
Project description:Cancer prevention by phenethyl isothiocyanate (PEITC) in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice [methyl-Seq]
| PRJNA589284 | ENA
Project description:Cancer prevention by phenethyl isothiocyanate (PEITC) in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice [RNA-Seq]
| PRJNA589285 | ENA
Project description:Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has been shown to have anti-tumor properties. In the present study, we investigated whether BITC inhibits the development of prostate cancer in the transgenic adenocarcinoma mouse prostate (TRAMP) mice. Five-week old, male TRAMP mice and their nontransgenic littermates were gavage-fed with 0, 5, or 10 mg/kg of BITC every day for 19 weeks. The weight of the genitourinary tract increased markedly in TRAMP mice and this increase was suppressed significantly by BITC feeding. H and E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC) was a predominant feature in the TRAMP mice. The number of lobes with WDC was reduced by BITC feeding while that of lobes with prostatic intraepithelial neoplasia was increased. BITC feeding reduced the number of cells expressing Ki67 (a proliferation marker), cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 in the prostatic tissue. In vitro cell culture results revealed that BITC decreased DNA synthesis, as well as CDK2 and CDK4 activity in TRAMP-C2 mouse prostate cancer cells. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in TRAMP mice treated with BITC.
| S-EPMC4783993 | biostudies-literature
Project description:Cruciferous vegetables have been associated with the chemoprevention of cancer. Epigenetic regulators have been identified as important targets for prostate cancer chemoprevention. Treatment of human prostate cancer cells with sulforaphane (SFN), a chemical from broccoli and broccoli sprouts, inhibits epigenetic regulators such as histone deacetylase (HDAC) enzymes, but it is not known whether consumption of a diet high in broccoli sprouts impacts epigenetic mechanisms in an in vivo model of prostate cancer.In the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, we tested the hypothesis that a broccoli sprout diet suppresses prostate cancer, inhibits HDAC expression, alters histone modifications, and changes the expression of genes regulated by HDACs.TRAMP mice were fed a 15% broccoli sprout or control AIN93G diet; tissue samples were collected at 12 and 28 wk of age.Mice fed broccoli sprouts had detectable amounts of SFN metabolites in liver, kidney, colon, and prostate tissues. Broccoli sprouts reduced prostate cancer incidence and progression to invasive cancer by 11- and 2.4-fold at 12 and 28 wk of age, respectively. There was a significant decline in HDAC3 protein expression in the epithelial cells of prostate ventral and anterior lobes at age 12 wk. Broccoli sprout consumption also decreased histone H3 lysine 9 trimethylation in the ventral lobe (age 12 wk), and decreased histone H3 lysine 18 acetylation in all prostate lobes (age 28 wk). A decline in p16 mRNA levels, a gene regulated by HDAC3, was associated with broccoli sprout consumption, but no significant changes were noted at the protein level.Broccoli sprout intake was associated with a decline in prostate cancer occurrence and HDAC3 protein expression in the prostate, extending prior work that implicated loss of HDAC3/ corepressor interactions as a key preventive mechanism by SFN in vivo.
| S-EPMC6041877 | biostudies-other
Project description:Surfactant protein D (SP-D), a pattern recognition molecule, is emerging as a potent anti-tumoural innate immune defense molecule in a range of cancers. Previously, SP-D expression was found to be significantly downregulated at the malignant sites of human prostate adenocarcinoma and associated with an increasing Gleason score and severity. We recently reported selective induction of intrinsic apoptosis by a recombinant fragment of human SP-D (rfhSP-D) in the human Prostate cancer (PCa) biopsy explants and cells with glucose regulated protein of 78 (GRP78) as one of the key interacting partners. The present study evaluated the expression of SP-D in early and advanced stages of PCa using transgenic adenocarcinoma of mouse prostate (TRAMP) model. Both early and late stages of PCa showed significantly decreased SP-D mRNA expression and increased proteolytic degradation of SP-D protein. Systemic and tumoural immunophenotyping of TRAMP model revealed increased serine proteases producing granulocytes and polymorphonuclear myeloid-derived suppressor cells (PMN MDSCs) in the late stage; the serine proteases secreted by these cells could be involved in the degradation of SP-D. Susceptibility of rfhSP-D to elastase-mediated proteolysis provided the rationale to use an elastase-inhibitor to sustain intact rfhSP-D in the tumour microenvironment. The study revealed an immunomodulatory potential of rfhSP-D and elastase inhibitor, sivelestat, to induce macrophage polarization towards M1 with downregulation of PMN MDSCs in ex-vivo cultured TRAMP tumours. Furthermore, rfhSP-D induced immunogenic cell death in murine PCa cells and in TRAMP explants. The findings highlight that SP-D plays an anti-tumourigenic role in PCa by inducing immunogenic cell death and immunomodulation while the prostate tumour milieu adversely impacts SP-D by inhibiting its transcription, and enhancing its proteolytic degradation. Transformation of an immunologically “cold tumour” into a “hot tumour” implicates therapeutic potential of rfhSP-D in PCa.
| S-EPMC9302643 | biostudies-literature
Project description:BackgroundThis study was undertaken to determine the chemopreventative efficacy of phenethyl isothiocyanate (PEITC), a bioactive constituent of many edible cruciferous vegetables, in a mouse model of prostate cancer, and to identify potential biomarker(s) associated with PEITC response.MethodsThe chemopreventative activity of dietary PEITC was investigated in Transgenic Adenocarcinoma of Mouse Prostate mice that were fed a control diet or one containing 3 μmol PEITC/g (n = 21 mice per group) for 19 weeks. Dorsolateral prostate tissue sections were stained with hematoxylin and eosin for histopathologic evaluations and subjected to immunohistochemistry for analysis of cell proliferation (Ki-67 expression), autophagy (p62 and LC3 protein expression), and E-cadherin expression. Autophagosomes were visualized by transmission electron microscopy. Apoptotic bodies were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Plasma proteomics was performed by two-dimensional gel electrophoresis followed by mass spectrometry to identify potential biomarkers of PEITC activity. All statistical tests were two-sided.ResultsAdministration of PEITC (3 μmol/g diet) decreased incidence (PEITC diet vs control diet, mean = 21.65 vs 57.58%, difference = -35.93%, 95% confidence interval = -45.48% to -13.10%, P = .04) as well as burden (affected area) (PEITC diet vs control diet, mean = 18.53% vs 45.01%, difference = -26.48%, 95% confidence interval = -49.78% to -3.19%, P = .02) of poorly differentiated tumors in the dorsolateral prostate of transgenic mice compared with control mice, with no toxic effects. PEITC-mediated inhibition of prostate carcinogenesis was associated with induction of autophagy and overexpression of E-cadherin in the dorsolateral prostate. However, PEITC treatment was not associated with a decrease in cellular proliferation, apoptosis induction, or inhibition of neoangiogenesis. Plasma proteomics revealed distinct changes in the expression of several proteins (eg, suppression of clusterin protein) in the PEITC-treated mice compared with control mice.ConclusionsIn this transgenic model, dietary PEITC suppressed prostate cancer progression by induction of autophagic cell death. Potential biomarkers to assess the response to PEITC treatment in plasma were identified.
| S-EPMC3071352 | biostudies-literature
Project description:We have previously reported alleviation of dextran sodium sulfate (DSS)-induced ulcerative colitis signs in phenethyl isothiocyanate (PEITC)-treated mice. Here we investigated chemoprotective activities of PEITC in mice with Azoxymethane-DSS induced colitis associated colon carcinogenesis. We also examined the molecular mediators associated with the PEITC effects using relevant cell lines. A 0.12% PEITC-enriched mouse-diet reduced mucosal and submucosal inflammation as well as glandular atypia by 12% and the frequency of adenocarcinoma by 17% with a concomitant improvement in overall disease activity indices compared to the diseased control group. Lipopolysaccharide-induced in vitro up-regulation of key mediators of inflammation, immune response, apoptosis, and cell proliferation were attenuated by 10 μM PEITC. Three of these mediators showed concentration-dependent reduction in respective mRNAs. Furthermore, PEITC inhibited Nuclear factor kappa B1 (NFκB1) proteins in a concentration-dependent manner. The NFκB1 mRNA expression inversely correlated ( r = −0.940, p = 0.013) with tri-methylation of lysine 27 on histone 3 near its promoter region in a time-dependent manner. These results indicate that PEITC may slow down the development of colon carcinogenesis in an inflammatory intestinal setting which is potentially associated with epigenetic modulation of NFκB1 signaling.
| S-EPMC5618557 | biostudies-literature