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High- and low-Molecular Weight oat Beta-Glucan Reveals Antitumor Activity in Human Epithelial Lung Cancer.

ABSTRACT: Beta-glucans are widely used in treatment, cosmetics, and the food industry. Glucans play a significant role in activation of the immune and antioxidant system and inhibiting tumor proliferation. In the current study the antitumor activities of new high and low molecular weight beta-glucan derived from oats were investigated in two human lung cancer cell line (A549, H69AR) and normal keratinocytes (HaCaT). The effect of high and low molecular weight beta-glucan from oat was evaluated by cellular viability assessment, lipid peroxidation and manganese superoxide dismutase evaluation and cytoskeleton visualisation. Additionally the level of red blood cells hemolysis was performed. Our results indicate strong anti-tumor properties of new beta-glucan from oat and at the same time no toxicity for normal cells.

SUBMITTER: Choromanska A

PROVIDER: S-EPMC5972159 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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High- and low-Molecular Weight oat Beta-Glucan Reveals Antitumor Activity in Human Epithelial Lung Cancer.

Choromanska Anna A Kulbacka Julita J Harasym Joanna J Oledzki Remigiusz R Szewczyk Anna A Saczko Jolanta J

Pathology oncology research : POR 20170729 3

Beta-glucans are widely used in treatment, cosmetics, and the food industry. Glucans play a significant role in activation of the immune and antioxidant system and inhibiting tumor proliferation. In the current study the antitumor activities of new high and low molecular weight beta-glucan derived from oats were investigated in two human lung cancer cell line (A549, H69AR) and normal keratinocytes (HaCaT). The effect of high and low molecular weight beta-glucan from oat was evaluated by cellular ...[more]

PMID: 28756506

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Project description:The physiological cholesterol-lowering benefits of β-glucan have been well documented, however, whether modulation of gut microbiota by β-glucan is associated with these physiological effects remains unknown. The objectives of this study were therefore to determine the impact of β-glucan on the composition of gut microbiota in mildly hypercholesterolemic individuals and to identify if the altered microbiota are associated with bioactivity of β-glucan in improving risk factors of cardiovascular disease (CVD). Using a randomized, controlled crossover study design, individuals received for 5-week either a treatment breakfast containing 3 g high molecular weight (HMW), 3 g low molecular weight (LMW), 5 g LMW barley β-glucan, or wheat and rice. The American Heart Association (AHA) diet served as the background diet for all treatment groups. Phases were separated by 4-week washout periods. Fecal samples were collected at the end of each intervention phase and subjected to Illumina sequencing of 16S rRNA genes. Results revealed that at the phylum level, supplementation of 3 g/d HMW β-glucan increased Bacteroidetes and decreased Firmicutes abundances compared to control (P < 0.001). At the genus level, consumption of 3 g/d HMW β-glucan increased Bacteroides (P < 0.003), tended to increase Prevotella (P < 0.1) but decreased Dorea (P < 0.1), whereas diets containing 5 g LMW β-glucan and 3 g LMW β-glucan failed to alter the gut microbiota composition. Bacteroides, Prevotella, and Dorea composition correlated (P < 0.05) with shifts of CVD risk factors, including body mass index, waist circumference, blood pressure, as well as triglyceride levels. Our data suggest that consumption of HMW β-glucan favorably alters the composition of gut microbiota and this altered microbiota profile associates with a reduction of CVD risk markers. Together, our study suggests that β-glucan induced shifts in gut microbiota in a MW-dependent manner and that might be one of the underlying mechanisms responsible for the physiological benefits of β-glucan.

Project description:PURPOSE:Beta-glucans are biologically active polysaccharides having antioxidant, immunomodulatory, and antiinflammatory properties. This study investigated the transcriptomic profile in peripheral blood of rats with LPS-induced enteritis, which were fed a diet supplemented with high- (G1) and low- (G2) molecular-weight oat beta-glucans. METHODS:Two-color rat gene expression microarrays were applied and the analysis was performed using a common reference design to provide easy means of comparing samples from various experimental conditions against one another. Common reference sample was labeled with cyanine 3 (Cy3) and investigated samples from each experimental group: C-G0 (control group fed semi-synthetic diet), LPS-G0 (LPS-challenged group fed semi-synthetic diet), LPS-G1 (LPS-challenged group fed G1 beta-glucan enriched diet), and LPS-G2 (LPS-challenged group fed G2 beta-glucan enriched diet) were labeled with cyanine 5 (Cy5). Each microarray was performed in quadruplicate. Statistical analysis was performed using one-way ANOVA and Tukey's HSD post-hoc test (p?<?0.05). A multiple testing correction was performed using Benjamini and Hochberg False Discovery Rate?<?5%. A quantitative real-time RT-PCR was performed to verify the expression of chosen transcripts. RESULTS:The microarray analyses revealed differentially expressed transcripts between: the LPS-G0 and the control groups: C-G0 (138 genes), the LPS-G1 and LPS-G0 groups (533 genes), and the LPS-G2 and LPS-G0 groups (97 genes). Several differentially expressed genes in the beta-glucan-supplemented groups encoded proteins belonging to TLR and NLR signaling pathways, as well as prostaglandin synthesis and regulation pathways. Both beta-glucans up-regulated the expression of Atg10, which belongs to the family of autophagy-related genes, suggesting a possible link between autophagy induction and beta-glucan supplementation. CONCLUSION:The changes in gene expression observed in the peripheral blood indicate that oat beta-glucans exerted a protective effect in rats with an induced inflammatory state caused by LPS challenge. The greater number of differentially expressed genes was observed in group supplemented with G1 beta-glucan, pointing at the differences in the mode of action of high- and low-molecular-weight beta-glucans in the organism.

Project description:Background & Aims: Non-alcoholic fatty liver disease (NALFLD)-associated changes in gut microbiota are important drivers of disease progression toward fibrosis. Therefore, reversing microbiota alterations could ameliorate NAFLD progression. Oat beta-glucan, a non-digestible polysaccharides, has shown promising therapeutic effects on hyperlipidemia associated with NAFLD, but its impact on gut microbiota and most importantly NAFLD fibrosis remains unknown. Methods: We performed detailed metabolic phenotyping including body composition, glucose tolerance, and lipid metabolism as well as comprehensive characterization of the gut-liver axis in a western-style diet (WSD)-induced model of NAFLD and assessed the effect of a beta-glucan intervention on early and advanced liver disease. Gut microbiota was modulated using broad-spectrum antibiotic (Abx) treatment. Results: Oat beta-glucan supplementation did not affect WSD-induced body weight gain, glucose intolerance, and the metabolic phenotype remained largely unaffected. Interestingly, oat beta-glucan dampened NAFLD inflammation, associated with significantly reduced monocyte-derived macrophages (MoMFs) infiltration, fibroinflammatory gene expression, and strongly reduced fibrosis development. Mechanistically, this protective effect was not mediated by changes in bile acid composition or signaling, but was dependent on gut microbiota and was lost upon Abx treatment. Specifically, oat beta-glucan partially reversed unfavorable changes in gut microbiota, resulting in an expansion of protective taxa, including Ruminococcus, and Lactobacillus followed by reduced translocation of TLR ligands. Conclusions: Our findings identify oat beta-glucan as a highly efficacious food supplement that dampens inflammation and fibrosis development in diet-induced NAFLD. These results, along with its favorable dietary profile, suggest that it may be a cost-effective and well-tolerated approach to preventing NAFLD progression and should be assessed in clinical studies.

Project description:BackgroundHealth claims regarding the cholesterol-lowering effect of soluble fiber from oat products, approved by food standards agencies worldwide, are based on a diet containing ≥3 g/d of oat β-glucan (OBG). Given the number of recently published randomized controlled trials (RCTs), it is important to update the findings of previous meta-analyses.ObjectiveThe objective was to quantify the effect of ≥3 g OBG/d on serum cholesterol concentrations in humans and investigate potential effect modifiers.DesignA meta-analysis was performed on 28 RCTs comparing ≥3 g OBG/d with an appropriate control. Systematic searches were undertaken in PubMed, AGRICOLA, and Scopus between 1 January 1966 and 6 June 2013, plus in-house study reports at CreaNutrition AG. Studies were assessed with regard to inclusion/exclusion criteria, and data were extracted from included studies by reviewers working independently in pairs, reconciling differences by consensus. Estimates of the mean reduction in serum cholesterol from baseline between the OBG and control diets were analyzed by using random-effects meta-analysis models and meta-regression.ResultsOBG in doses of ≥3 g/d reduced low-density lipoprotein (LDL) and total cholesterol relative to control by 0.25 mmol/L (95% CI: 0.20, 0.30; P < 0.0001) and 0.30 mmol/L (95% CI: 0.24, 0.35; P < 0.0001), respectively, with some indication of heterogeneity (P = 0.13 and P = 0.067). There was no significant effect of OBG on high-density lipoprotein (HDL) cholesterol or triglycerides and no evidence that dose (range across trials: 3.0-12.4 g/d) or duration of treatment (range: 2-12 wk) influenced the results. LDL cholesterol lowering was significantly greater with higher baseline LDL cholesterol. There was a significantly greater effect for both LDL and total cholesterol in subjects with diabetes compared with those without (although based on few studies).ConclusionsAdding ≥3 g OBG/d to the diet reduces LDL and total cholesterol by 0.25 mmol/L and 0.30 mmol/L, respectively, without changing HDL cholesterol or triglycerides.

Dataset Information

High- and low-Molecular Weight oat Beta-Glucan Reveals Antitumor Activity in Human Epithelial Lung Cancer.

Publications

High- and low-Molecular Weight oat Beta-Glucan Reveals Antitumor Activity in Human Epithelial Lung Cancer.

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