Biological Profile of Erucin: A New Promising Anticancer Agent from Cruciferous Vegetables

Consumption of cruciferous vegetables has been associated with a reduced risk in the development of various types of cancer. This has been attributed to the bioactive hydrolysis products that are derived from these vegetables, namely isothiocyanates. Erucin is one such product derived from rocket salads, which is structurally related to sulforaphane, a well-studied broccoli-derived isothiocyanate. In this review, we present current knowledge on mechanisms of action of erucin in chemoprevention obtained from cell and animal models and relate it to other isothiocyanates. These mechanisms include modulation of phase I, II and III detoxification, regulation of cell growth by induction of apoptosis and cell cycle arrest, induction of ROS-mechanisms and regulation androgen receptor pathways

The dietary isothiocyanate sulforaphane modulates gene expression and alternative gene splicing in a PTEN null preclinical murine model of prostate cancer

<p>Abstract</p> <p>Background</p> <p>Dietary or therapeutic interventions to counteract the loss of PTEN expression could contribute to the prevention of prostate carcinogenesis or reduce the rate of cancer progression. In this study, we investigate the interaction between sulforaphane, a dietary isothiocyanate derived from broccoli, PTEN expression and gene expression in pre malignant prostate tissue.</p> <p>Results</p> <p>We initially describe heterogeneity in expression of PTEN in non-malignant prostate tissue of men deemed to be at risk of prostate cancer. We subsequently use the mouse prostate-specific PTEN deletion model, to show that sulforaphane suppresses transcriptional changes induced by PTEN deletion and induces additional changes in gene expression associated with cell cycle arrest and apoptosis in PTEN null tissue, but has no effect on transcription in wild type tissue. Comparative analyses of changes in gene expression in mouse and human prostate tissue indicate that similar changes can be induced in humans with a broccoli-rich diet. Global analyses of exon expression demonstrated that sulforaphane interacts with PTEN deletion to modulate alternative gene splicing, illustrated through a more detailed analysis of DMBT1 splicing.</p> <p>Conclusion</p> <p>To our knowledge, this is the first report of how diet may perturb changes in transcription induced by PTEN deletion, and the effects of diet on global patterns of alternative gene splicing. The study exemplifies the complex interaction between diet, genotype and gene expression, and the multiple modes of action of small bioactive dietary components.</p

Accumulation of Dietary S-Methyl Cysteine Sulfoxide in Human Prostate Tissue

Scope: Observational studies have associated consumption of cruciferous vegetables with reduced risk of prostate cancer. This effect has been associated with the degradation products of glucosinolates—thioglycosides that accumulate within crucifers. The possible role of S-methyl cysteine sulfoxide, a metabolite that also accumulates in cruciferous vegetables, and its derivatives, in cancer prevention is relatively unexplored compared to glucosinolate derivatives. The hypothesis that consuming a broccoli soup results in the accumulation of sulfate (a SMCSO derivative) and other broccoli-derived metabolites in prostate tissue is tested. Methods and results: Eighteen men scheduled for transperineal prostate biopsy were recruited into a 4-week parallel single blinded diet supplementation study (NCT02821728). Nine men supplemented their diet with three 300 mL portions of a broccoli soup each week for four weeks prior to surgery. Analyses of prostate biopsy tissues reveal no detectable levels of glucosinolates and derivatives. In contrast, SMCSO is detected in prostate tissues of the participants, with significantly higher levels in tissue of men in the supplementation arm. SMCSO was also found in blood and urine samples from a previous intervention study with the identical broccoli soup. Conclusion: The consequences of SMCSO accumulation in prostate tissues and its potential role in prevention of prostate cancer remains to be investigated

Transcriptional changes in prostate of men on active surveillance after a 12-mo glucoraphanin-rich broccoli intervention—results from the Effect of Sulforaphane on prostate CAncer PrEvention (ESCAPE) randomized controlled trial

Background Epidemiological evidence suggests that consumption of cruciferous vegetables is associated with reduced risk of prostate cancer progression, largely attributed to the biological activity of glucosinolate degradation products, such as sulforaphane derived from glucoraphanin. Because there are few therapeutic interventions for men on active surveillance for prostate cancer to reduce the risk of cancer progression, dietary approaches are an appealing option for patients. Objective We evaluated whether consumption of a glucoraphanin-rich broccoli soup for 1 y leads to changes in gene expression in prostate tissue of men with localized prostate cancer. Methods Forty-nine men on active surveillance completed a 3-arm parallel randomized double-blinded intervention study for 12 mo and underwent transperineal template biopsy procedures and dietary assessment at the start and end of the study. Patients received a weekly 300 mL portion of soup made from a standard broccoli (control) or from 1 of 2 experimental broccoli genotypes with enhanced concentrations of glucoraphanin, delivering 3 and 7 times that of the control, respectively. Gene expression in tissues from each patient obtained before and after the dietary intervention was quantified by RNA sequencing followed by gene set enrichment analyses. Results In the control arm, there were several hundred changes in gene expression in nonneoplastic tissue during the 12 mo. These were associated with an increase in expression of potentially oncogenic pathways including inflammation processes and epithelial–mesenchymal transition. Changes in gene expression and associated oncogenic pathways were attenuated in men on the glucoraphanin-rich broccoli soup in a dose-dependent manner. Although the study was not powered to assess clinical progression, an inverse association between consumption of cruciferous vegetables and cancer progression was observed. Conclusion Consuming glucoraphanin-rich broccoli soup affected gene expression in the prostate of men on active surveillance, consistent with a reduction in the risk of cancer progression. This trial was registered at clinicaltrials.gov as NCT01950143

Probing the Interstellar Medium in Early type galaxies with ISO observations

Four IRAS-detected early type galaxies were observed with ISO. With the exception of the 15 micron image of NGC1052, the mid-IR emission from NGC1052, NGC1155, NGC5866 and NGC6958 at 4.5, 7 and 15 microns show extended emission. Mid-IR emission from NGC1052, NGC1155, and NGC6958 follows a de Vaucouleurs profile. The ratio of 15/7 micron flux decreases with radius in these galaxies, approaching the values empirically observed for purely stellar systems. In NGC5866, the 7 and 15 micron emission is concentrated in the edge-on dust lane. All the galaxies are detected in the [CII] line, and the S0s NGC1155 and NGC5866 are detected in the [OI] line as well. The ISO-LWS observations of the [CII] line are more sensitive measures of cool, neutral ISM than HI and CO by about a factor of 10-100. Three of four early type galaxies, namely NGC1052, NGC6958 and NGC5866, have low ratio FIR/Blue and show a lower [CII]/FIR, which is due to a softer radiation field from old stellar populations. The low [CII]/CO ratio in NGC5866 ([CII]/CO(1-0) < 570) confirms this scenario. We estimate the UV radiation expected from the old stellar populations in these galaxies and compare it to that needed to heat the gas to account for the cooling observed [CII] and [OI] lines. In three out of four galaxies, NGC1052, NGC5866 and NGC6958, the predicted UV radiation falls short by a factor of 2-3. In view of the observed intrinsic scatter in the "UV-upturn" in elliptical galaxies and its great sensitivity to age and metallicity effects, this is not significant. However, the much larger difference (about a factor of 20) between the UV radiation from old stars and that needed to produce the FIR lines for NGC 1155 is strong evidence for the presence of young stars, in NGC1155.Comment: To appear in the Astrophysical Journal. Figure 1 appears as a separate jpg figur

Cyclin-dependent Kinase Inhibitor p21 is a Crucial Molecular Target for the Potential Antitumor Efficacy of Erucin from Rocket Salad Species against Prostate Cancer

Trabajo presentado en Messina (Italia) en Junio del 2010.-- et al.Peer reviewe

Promising selectivity of dietary isothiocyanates from cruciferous vegetables for human cancer cells

Trabajo presentado al FITOMED celebrado en Messina (Italia) en Junio del 2010.- Melchini, Antonietta et al.Peer reviewe

Promising selectivity of dietary isothiocyanates from cruciferous vegetables for human cancer cells

Trabajo presentado al FITOMED celebrado en Messina (Italia) en Junio del 2010.- Melchini, Antonietta et al.Peer reviewe

Enhanced in Vitro Biological Activity of Synthetic 2‑(2-Pyridyl) Ethyl Isothiocyanate Compared to Natural 4‑(Methylsulfinyl) Butyl Isothiocyanate

Dietary isothiocyanates (ITC) derived from cruciferous vegetables have been shown to have numerous biological effects consistent with chemoprotective activity. In this study we synthesized a novel ITC, 2-(2-pyridyl) ethyl ITC (PY-ITC), and assessed its chemopreventive ability in comparison to sulforaphane (SF), the ITC derived from broccoli. PY-ITC suppressed cancerous cell growth and proliferation at lower concentrations than SF and was more potent at inducing p21 protein. Through the use of whole genome arrays we demonstrate that prostate cells exposed to PY-ITC or SF have similar biological response, albeit PY-ITC alters a greater number of genes, and to a greater extent. In the presence of a phosphatidylinositol-3-kinase (PI3K) inhibitor PY-ITC had a more pronounced effect on gene expression, emphasizing the important role of PI3K/AKT signaling in mediating the chemopreventive effects of ITCs. These results highlight the importance of the ITC side chain in bioactivity

INTEGRATING TRANSCRIPTOME AND METABOLOME SIGNATURES TO PROVIDE NEW INSIGHTS AS TO HOW DIET CAN PREVENT PROSTATE CANCER PROGRESSION

Although there is an increase in the diagnosis of prostate cancer, most tumours remain organ-confined with little consequence to health. However, if highly aggressive clones emerge, this is a poor health prognosis. Genomic studies have demonstrated that many mutations occur in what appears to be non-cancerous tissues, and metastatic cancer may arise from relatively small tumours, with larger tumours remaining confined to the prostate. We are seeking to understand why the prostate gland becomes susceptible to multifocal carcinogenesis, and how diet may affect the tumour microenvironment to reduce the risk of emergence of aggressive clones. We report results from an intervention study designed to investigate dietary factors that reduce the risk of cancer progression. Men who had a diagnosis of organ-confined prostate cancer underwent a transperineally template biopsy before and after a 12-month dietary intervention with a soup developed from glucosinolate-enriched broccoli, along with appropriate control diets. Habitual diet was rigorously assessed through repeated seven-day diet diaries. Biopsy tissue was assessed for cancer progression, metabolome and transcriptome profiles, and quantification of targeted metabolites. The results provide insight into specific components of cruciferous vegetables that may influence the risk of cancer progression and the underlying mechanisms