Anti-Cancer Potential of Linear ß-(1→6)-D-Glucan from Agaricus bisporus on Estrogen Receptor-Positive (ER+) Breast Cancer Cells.

Mushroom ß-D-glucans can be isolated from several species, including the widely consumed Agaricus bisporus. Besides immunomodulatory responses, some ß-D-glucans may exhibit direct antitumoral effects. It was previously observed that a ß-(1→6)-D-glucan (BDG16) has indirect cytotoxicity on triple-negative breast cancer cells. In this study, the cytotoxicity of this same glucan was observed on estrogen receptor-positive (ER+) breast cancer cells (MCF-7). Cell viability was determined by multiple methods to assess metabolic activity, lysosomal membrane integrity, and adhesion capacity. Assays to evaluate cell respiration, cell cycle, apoptosis, necroptosis, and oxidative stress were performed to determine the action of BDG16 on MCF-7 cells. A gradual and significant cell viability reduction was observed when the cells were treated with BDG16 (10-1000 µg/mL). This result could be associated with the inhibition of the basal state respiration after incubation with the ß-D-glucan. The cells showed a significant arrest in G1 phase population at 1000 µg/mL, with no induction of apoptosis. However, an increase in necrosis and necroptosis at the same concentration was observed. No difference in oxidative stress-related molecules was observed. Altogether, our findings demonstrate that BDG16 directly induces toxicity in MCF-7 cells, primarily by impairing mitochondrial respiration and promoting necroptosis. The specific mechanisms that mediate this action are being investigated.

Specific dietary fibers prevent heavy metal disruption of the human gut microbiota in vitro.

Heavy metal exposure is a growing concern due to its adverse effects on human health, including the disruption of gut microbiota composition and function. Dietary fibers have been shown to positively impact the gut microbiota and could mitigate some of the heavy metal negative effects. This study aimed to investigate the effects of different heavy metals (As, Cd and Hg in different concentrations) on gut microbiota in the presence and absence of different dietary fibers that included fructooligosaccharides, pectin, resistant starch, and wheat bran. We observed that whereas heavy metals impaired fiber fermentation outcomes for some fiber types, the presence of fibers generally protected gut microbial communities from heavy metal-induced changes, especially for As and Cd. Notably, the protective effects varied depending on fiber types, and heavy metal type and concentration and were overall stronger for wheat bran and pectin than other fiber types. Our findings suggest that dietary fibers play a role in mitigating the adverse effects of heavy metal exposure on gut microbiota health and may have implications for the development of dietary interventions to reduce dysbiosis associated with heavy metal exposure. Moreover, fiber-type specific outcomes highlight the importance of evidence-based selection of prebiotic dietary fibers to mitigate heavy metal toxicity to the gut microbiota.

Agaricus bisporus ß-(1 → 6)-d-glucan induces M1 phenotype on macrophages and increases sensitivity to doxorubicin of triple negative breast cancer cells.

Mushroom ß-d-glucans have demonstrated immunomodulatory activity, which is initiated by their recognition by specific receptors on immune system cells surfaces. Studies indicated that ß-d-glucans may present a synergistic effect with chemotherapy drugs. In this study, a linear ß-(1 â†’ 6)-d-glucan (B16), isolated from A. bisporus and previously characterized (Mw: 8.26 × 104 g/mol), was evaluated about its capacity to modulate THP-1 macrophages towards an M1 phenotype and induce an antitumoral activity. This was evidenced by the production of pro-inflammatory markers upon B16 treatment (30; 100 µg/mL). The breast tumor cells (MDA-MB-231) viability was not affected by treatment with B16, however, their viability markedly decreased upon treatment with the drug doxorubicin. The results showed a synergic effect of B16 and doxorubicin, which reduced the viability of MDA-MB-231 cells by 31%. Furthermore, B16 treatment provided a sustainable M1 state environment and contributed to increase the sensitivity of breast cancer cells to the doxorubicin treatment.

Heavy metal contamination and health risk assessment in grains and grain-based processed food in Arequipa region of Peru.

Heavy metals (HMs) in crops and processed foods are a concern and pose a potential serious health hazard. This study investigated possible presence of HMs in grains and processed products in the Region of Arequipa in Peru. Concentrations of Cd, As, Sn, Pb, and Hg were determined for commonly consumed grains in 18 districts of the region and processed products from 3 popular markets of Arequipa city, using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Cold Vapor Atomic Absorption Spectroscopy (CVAAS). HM concentrations above the Codex General Standard limits were found for As (0.17 mg kg-1) and Cd (0.11 mg kg-1) in cereal grains. Elevated Pb concentrations of 0.55, 0.75, and 5.08 mg kg-1 were found for quinoa, maize, and rice products, respectively; and attributed to processing conditions. The Total Hazard Index (HI) for polished rice and rice products had values between 1 and 10, showing non-carcinogenic adverse effects. Total Target Cancer Risk (TRT) and uncertainty analysis of percentile P90% for polished rice and quinoa products gave values above permissible limit of 10-4, indicating an unacceptable cancer risk. The Nemerow Composite Pollution Index method (NCPI) showed that processed products had a significant pollution level due to the presence of Pb. While most crops grains had acceptable low HM levels, this is the first report of concerning HM concentrations in some consumed grains and processed products in southern Peru and indicates the necessity to find ways to decrease certain toxic metals in foods.

Sulfation of fucogalactan from Agaricus bisporus: Different patterns in the chemical structure and their effects on anticoagulant activity.

A fucogalactan from Agaricus bisporus was sulfated by two methodologies based on an optimized sulfation method. The direct action of chlorosulfonic acid and SO3-pyridine complex over the sulfation reaction and its effects on anticoagulant activity were evaluated. The products of chemical sulfations were two sulfated fucogalactans named E100 and ESL respectively. Clotting assays (APTT, PT and TT) showed that both sulfated polysaccharides have anticoagulant activity, and that ESL was more potent compared to E100. The FXa, T and FXIIa activities in the presence of the sulfated polysaccharides were determined. The better anticoagulant activity of ESL could be related to anti-FXIIa activity and also probably to its higher bioavailability. The HPSEC analysis showed similar Mw of 1.08×104gmol-1 and 1.00×104gmol-1 for E100 and ESL respectively. NMR and methylation analyses indicated a heterogeneous sulfation pattern for E100, whereas ESL showed conserved unsulfated (1→6)-linked α-d-Galp residues in the main-chain and a more homogeneous sulfation pattern. The DS values of ESL and E100 were 1.0 and 2.8 respectively, indicating that the sulfation pattern is more important for the anticoagulant activity than the amount of sulfate.