Vitamin E, γ-tocotrienol,Protects Against Buthionine Sulfoximine-Induced Cell Death by Scavenging Free Radicals in SH-SY5Y Neuroblastoma Cells

The induction of reactive oxygen species (ROS) to selectively kill cancer cells is an important feature of radiotherapy and various chemotherapies. Depletion of glutathione can induce apoptosis in cancer cells or sensitize them to anticancer treatments intended to modulate ROS levels. In contrast, antioxidants protect cancer cells from oxidative stress-induced cell death by scavenging ROS. The role of exogenous antioxidants in cancer cells under oxidative insults remains controversial and unclear. This study aimed to identify protective pathways modulated by γ-tocotrienol (γT3), an isomer of vitamin E, in human neuroblastoma SH-SY5Y cells under oxidative stress. Using buthionine sulfoximine (BSO) as an inhibitor of glutathione synthesis, we found that BSO treatment reduced the viability of SH-SY5Y cells. BSO induced cell death by increasing apoptosis, decreased the level of reduced glutathione (GSH), and increased ROS levels in SH-SY5Y cells. Addition of γT3 increased the viability of BSO-treated cells, suppressed apoptosis, and decreased the ROS level induced by BSO, while the GSH level was unaffected. These results suggest that decreasing GSH levels by BSO increased ROS levels, leading to apoptosis in SH-SY5Y cells. γT3 attenuated the BSO-induced cell death by scavenging free radicals.     

Lycopene and Apo-12′-Lycopenal Reduce Cell Proliferation and Alter Cell Cycle Progression in Human Prostate Cancer Cells

Lycopene is associated with a reduced risk of prostate cancer. However, lycopene may not be wholly responsible for the effects seen in vivo or in cell culture systems. Apo-lycopenals or other lycopene metabolites, whether produced by cleavage enzymes within the body or consumed with tomato products, can be found in tissues at concentrations equivalent to physiological retinoid concentrations. Therefore, it is plausible that lycopenoids, like retinoids, are bioactive within tissues. Androgen-independent DU145 prostate cancer cells were treated with lycopene, apo-8′-lycopenal, or apo-12′-lycopenal. DU145 cell proliferation was significantly reduced by supra-physiological levels of lycopene and apo-12′-lycopenal, in part, through alteration of the normal cell cycle. Levels of the gap junction protein, connexin 43, were unaltered by lycopene or apo-lycopenal treatment while cell apoptosis rates significantly decreased. We further confirmed that connexin 43 protein levels were unaltered by lycopene treatment in mouse embryonic fibroblasts, or in Dunning R3327-H rat prostate tumor. The present data indicate that lycopene and apo-12′-lycopenal reduce the proliferation of prostate cancer cells, in part, by inhibiting normal cell cycle progression.     

Olive Fruit Blends Modulate Lipid-Sensing Nuclear Receptor PPARγ, Cell Survival,and Oxidative Stress Response in Human Osteoblast Cells

Objective: The aim of the present study was to investigate how different extravirgin olive oils (EVOOs), obtained by blending Olea europea cultivars, could influence the cell growth, the response to inflammatory stimuli, and oxidative stress in a culture of the osteosarcoma cell line Saos-2.

Methods: Three different extravirgin olive oils were physicochemically characterized, determining the free acidity, the oxidation status, the polyphenols content, and the antioxidative activity. Moreover, the effects on Saos-2 cell culture were determined, studying the mRNA expression level by real-time polymerase chain reaction (PCR) assays and the antioxidative activity using fluorescent probes.

Results: The cultivars used in the south of Italy, yield extravirgin oils with different amount of fatty acids and polyphenols, which counteract induction of proinflammatory cytokines and regulate free radical production in hydrogen peroxide-stimulated cells. In vitro analysis using the human osteoblast cell line Saos-2 showed that the addition of oils to cell culture simulated a hypoxic stress followed by a reoxygenation period, during which the antioxidant activity of extravirgin olive oils protected cells from oxidative damages. On the other hand, the mRNA expression levels of factors involved in inflammatory processes, cell growth recovery, and antioxidant response, as heme oxygenase-1, were differently stimulated by EVOOs. Moreover, peroxisome proliferator activated receptor γ (PPARγ) was differently modulated by EVOOs.

Conclusion: These findings show that the blending of different extravirgin olive oil can impact an osteoblast cell line, in particular regarding cell growth recovery and oxidative stress.     

Maternal Exposure to Polycyclic Aromatic Hydrocarbons and 5'-CpG Methylation of Interferon-γ in Cord White Blood Cells

Background: Maternal factors are implicated in the onset of childhood asthma. Differentiation of naïve CD4⁺ T lymphocytes into pro-allergic T-helper 2 cells induces interleukin (IL)4 expression and inhibits interferon (IFN)γ expression accompanied by concordant methylation changes in the promoters of these genes. However, it has yet to be established whether maternal exposure to polycyclic aromatic hydrocarbons (PAHs) can alter these gene promoters epigenetically during fetal development.Objectives: In this study we sought to elucidate the relationship between maternal PAH exposure and promoter methylation status of IFNγ and IL4.Methods: We assessed the effects of benzo[a]pyrene (BaP), a representative airborne PAH, on the methylation status of the IFNγ and IL4 promoters in Jurkat cells and two lung adenocarcinoma cell lines, and on gene expression. In addition, we evaluated methylation status of the IFNγ promoter in cord white blood cells from 53 participants in the Columbia Center for Children’s Environmental Health cohort. Maternal PAH exposure was estimated by personal air monitoring during pregnancy.Results: In vitro exposure of the cell models to low, noncytotoxic doses (0.1 and 1 nM) of BaP elicited increased promoter hypermethylation and reduced expression of IFNγ, but not IL4. IFNγ promoter methylation in cord white blood cells was associated with maternal PAH exposure in the cohort study subsample.Conclusion: Consistent with the results for the cell lines, maternal exposure to PAHs was associated with hypermethylation of IFNγ in cord blood DNA from cohort children. These findings support a potential role of epigenetics in fetal reprogramming by PAH-induced environmental diseases.     

Körperliche Aktivität in der Freizeit Deutsche Herz-Kreislauf-Präventionsstudie (DHP): Ergebnisse der Regionalen Gesundheitssurveys 1984/5 - 1988 -1991/2 für die Region Stuttgart

Objective

To test the hypothesis that community-oriented intervention programmes can promote physical leisure time activity.

Design Cross-sectional community-based multicentre intervention study

Setting

Health surveys in 1984/5,1988 and 1991/2 in Stuttgart-West and Vaihingen

Subjects

25–69 year old population in the GCP-study-region of Stuttgart. Main outcome Measurement and comparison of prevalences and odds ratios

measures

of physical inactivity in 1984/5,1988, 1991/2.

Results

Physical activity decreased in all socioeconomic strata.

Conclusions

In spite of prevention leisure time physical activity declined in Stuttgart.