Antiproliferative and Apoptosis Effects of Hybrid Varieties of Vitis vinifera L. Sweet Sapphire and Sweet Surprise on Human Prostate Cancer Cells Using In Vitro and In Silico Approaches.

OBJECTIVE: Grape hybrids are characterized by different chemical compositions; often with high hybrids are characterized by different chemical compositions, often with a high phenolic content and a specific profile of anthocyanins. The aim of study was to characterize the constituents of hybrid Vitis vinifera L. varieties Sweet Sapphire (SA) and Sweet Surprise (SU) extracts and their influence on apoptosis induction and antiproliferative effects on human prostate cancer cells. METHODS: We used the MTT assay to evaluate the cytotoxic effect of extracts of SA and SU, on the prostate adenocarcinoma cell lines PC-3 and DU-145. To analyze the inhibiting impact by flow cytometry, used 24 and 48 hours. Anthocyanins were quantified by liquid chromatography and analysed by their absorption rate, hepatotoxicity, blood concentration, blood-brain barrier passage ability and maximum recommended dose by in silico approaches. RESULTS: Our results showed that malvidin derivatives present the highest content in both cultivars. We identified 14.46mg/100g malvidin-3-O-glycoside in SA and 2.76 mg/100 g in SU. A reduction in cell viability of DU-145 (45 and 65%) and PC-3 (63 and 67%) cells after 48h treatment with SA and SU, respectively, was found via MTT assay. Flow cytometry showed that the treatment with extracts from SA and SU had an inhibitory impact on cell development due to G2/M arrest and caused a rise in apoptotic cells compared to control group. None of the anthocyanin presented hepatotoxicity as well as blood-brain barrier passage ability. Peonidin 3-O-glucoside had the lower maximum recommended dose as well as the highest intestinal absorption rate. However, delphinidin 3-O-glucoside had the highest blood concentration values. CONCLUSION: The findings of this study highlight the potential of hybrid Vitis vinifera L. varieties as an important source of natural antioxidants and their protective effect against prostate cancer cells as well as elucidate in part their anthocyanin's metabolism.

Effect of Paternal Diet on Spermatogenesis and Offspring Health: Focus on Epigenetics and Interventions with Food Bioactive Compounds.

Infertility is a growing public health problem. Consumption of antioxidant bioactive food compounds (BFCs) that include micronutrients and non-nutrients has been highlighted as a potential strategy to protect against oxidative and inflammatory damage in the male reproductive system induced by obesity, alcohol, and toxicants and, thus, improve spermatogenesis and the fertility parameters. Paternal consumption of such dietary compounds could not only benefit the fathers but their offspring as well. Studies in the new field of paternal origins of health and disease show that paternal malnutrition can alter sperm epigenome, and this can alter fetal development and program an increased risk of metabolic diseases and breast cancer in adulthood. BFCs, such as ascorbic acid, α-tocopherol, polyunsaturated fatty acids, trace elements, carnitines, N-acetylcysteine, and coenzyme Q10, have been shown to improve male gametogenesis, modulate epigenetics of germ cells, and the epigenetic signature of the offspring, restoring offspring metabolic health induced by stressors during early life. This indicates that, from a father's perspective, preconception is a valuable window of opportunity to start potential nutritional interventions with these BFCs to maximize sperm epigenetic integrity and promote adequate fetal growth and development, thus preventing chronic disease in adulthood.

Selenium Supplementation during Puberty and Young Adulthood Mitigates Obesity-Induced Metabolic, Cellular and Epigenetic Alterations in Male Rat Physiology.

Selenium (Se) role in obesity is not clear. In addition, information on Se's role in male physiology, specifically in obesity, is scarce. We conducted this study to evaluate the efficacy of Se supplementation, specifically during puberty until young adulthood, against obesity-induced deregulation of metabolic, cellular, and epigenetic parameters in epididymal fat and/or sperm cells in a rat model. High-fat-diet consumption by male rats during puberty and young adulthood significantly increased body weight, adipocyte size, oxidative stress, deregulated expression of genes associated with inflammation (Adiponectin, IL-6, TNF-α), adipogenesis (CEBPα), estrogen biosynthesis (CYP19) and epigenetic processes in epididymal adipose tissue (Dnmt3a), as well as altered microRNA expression vital for spermatogenesis in sperm cells (miR-15b and miR-497). On the other hand, Se supplementation significantly decreased oxidative stress and mitigated these molecular/epigenetic alterations in epididymal adipose tissue or sperm cells. Our results indicate that selenium supplementation during puberty/young adulthood could improve male physiology in the context of obesity. In addition, it suggests that Se could potentially positively affect offspring health.

Bioactive food compounds, epigenetics and chronic disease prevention: Focus on early-life interventions with polyphenols.

Consumption of bioactive compounds such as polyphenols, isothiocyanates, sulfur-containing compounds and terpenoids, found in fruits and vegetables, is associated with prevention of chronic disease. These bioactive food compounds elicit their protective effects through complex mechanisms at the cellular and molecular, including epigenetic levels. According to the Developmental Origins of Health and Disease (DOHaD) paradigm, in utero exposure to stressors such as malnutrition through maternal diet would impair fetal development and epigenetically program increased risk of metabolic diseases and some cancers in adult life. In addition, a role for fathers´ diet during preconception on their offspring health and chronic disease susceptibility has also emerged. This highlights early life as a promising window of opportunity for starting dietary interventions focusing on preventing chronic diseases. However, knowledge on the potential beneficial impact of early life exposure to bioactive food compounds is limited. Among the studies that have investigated bioactive food compounds in the context of DOHaD, most have focused on the impact of dietary polyphenols. Thus, in this review we discuss experimental evidence supporting a role for the dietary polyphenols resveratrol, genistein, epigallocatechin-3-gallate and anthocyanins in chronic disease prevention considering a perspective from early-life interventions through maternal and paternal diets and focusing on epigenetics as a potential underlying mechanism.