The Main Structural Unit Elucidation and Immunomodulatory Activity In Vitro of a Selenium-Enriched Polysaccharide Produced by Pleurotus ostreatus.

In recent years, the structure of selenium-enriched polysaccharides and their application in immunomodulation have attracted much attention. In previous studies, we extracted and purified a novel selenium-enriched Pleurotus ostreatus polysaccharide called Se-POP-21, but its structure and immunomodulatory activity were still unclear. In this study, the main structural unit formula of Se-POP-21 was characterized by methylation analysis and an NMR experiment. The results showed that the backbone of Se-POP-21 was →[2,6)-α-D-Galp-(1→6)-α-D-Galp-(1]4→2,4)-ß-L-Arap-(1→[2,6)-α-D-Galp-(1→6)-α-D-Galp-(1]4→, branched chain of ß-D-Manp-(1→ and ß-D-Manp-(1→4)-ß-L-Arap-(1→ connected with →2,6)-α-D-Galp-(1→ and →2,4)-ß-L-Arap-(1→,respectively, through the O-2 bond. In vitro cell experiments indicated that Se-POP-21 could significantly enhance the proliferation and phagocytosis of RAW264.7 cells, upregulate the expression of costimulatory molecules CD80/CD86, and promote RAW264.7 cells to secrete NO, ROS, TNF-α, IL-1ß, and IL-6 by activating the NF-κB protein. The results of this study indicate that Se-POP-21 can effectively activate RAW264.7 cells. Thus, it has the potential to be used in immunomodulatory drugs or functional foods.

Inhibition on the growth of human MDA-MB-231 breast cancer cells in vitro and tumor growth in a mouse xenograft model by Se-containing polysaccharides from Pyracantha fortuneana.

Breast cancer is the second cause of cancer-related death among Women. Current therapies for breast cancer have adverse side-effects. Selenium (Se)-containing polysaccharides have multiple health benefits to humans. Pyracantha fortuneana (P. fortuneana) contains rich Se polysaccharides. We hypothesized that Se-containing polysaccharides from P. fortuneana possess anticancer activity on breast cancer via inhibiting growth and inducing apoptosis. This study aimed to assess the anticancer effect of Se-containing polysaccharides from P. fortuneana and the underlying mechanisms. Se-containing polysaccharides were purified. Their properties and monosaccharide compositions were analyzed. Their effects on cell growth, expression of cycle proteins, apoptosis and apoptosis-related protein, and tumor growth in mouse xenograft model were examined. This extract contained 93.7% (w/w) of carbohydrate, 2.1% (w/w) of uronic acid and 3.7µg/g of Se, and was considered as Se-conjugated polysaccharides (Se-PFPs). In vitro studies showed that treatment of triple negative breast cancer (TNBC) MDA-MB-231 cells with Se-PFPs (1) inhibited cell growth dose-dependently by arresting cells at G2 phase via inhibiting CDC25C-CyclinB1/CDC2 pathway; (2) caused apoptosis associated with increased p53, Bax, Puma and Noxa, decreased Bcl2, increased Bax/Bcl2 ratio and increased activities of caspases 3/9, suggesting its effect on p53-mediated cytochrome c-caspase pathway. Treatment of nude mice bearing MDA-MB-231-derived xenograft tumors with Se-PFPs significantly reduced tumor growth without altering body weight, confirming its antitumor activity without toxic side effects. Se-PFPs enhanced doxorubicin cytotoxic effects. It is concluded that Se-containing polysaccharides from P. fortuneana potently inhibit the growth and induce apoptosis of TNBC cells and can be potential anticancer agent for TNBC.

Selenium-enriched polysaccharides from Pyracantha fortuneana (Se-PFPs) inhibit the growth and invasive potential of ovarian cancer cells through inhibiting ß-catenin signaling.

Polysaccharides from medicinal plants exert antitumor activity in many cancers. Our previous study demonstrated that polysaccharides extracted from the selenium-enriched Pyracantha fortuneana (Se-PFPs) showed antiproliferative effect in breast cancer cell line. This study aimed to investigate the antitumor effect of Se-PFPs in ovarian cancer cells in vitro and in vivo. Se-PFPs could decrease cell viability, induce apoptosis, and inhibit migratory and invasive potentials in HEY and SKOV3 cells. These findings are supported by reduced expression of cyclin D1, Bcl-2 and MMP-9, enhanced cleavage of PARP and caspase-3, elevated activity of caspase-3 and caspase-9, and EMT (epithelial to mesenchymal transition) inhibition (elevated expression of E-cadherin and cytokeratin 19, and reduced expression of N-cadherin, vimentin, ZEB1 and ZEB2). Moreover, Se-PFPs inhibited xenografted tumor growth through inhibiting cell proliferation and inducing cell apoptosis. More importantly, Se-PFPs significantly reduced cytoplasmic ß-catenin particularly nuclear ß-catenin expression but increased ß-catenin phosphorylation in a GSK-3ß-dependent mechanism. Furthermore, ß-catenin knockdown exerted similar effects on cell proliferation and invasion as seen in Se-PFPs-treated cells, while ß-catenin overexpression neutralized the inhibitory effects of Se-PFPs on cell proliferation and invasion. Take together,Se-PFPs exert antitumor activity through inhibiting cell proliferation, migration, invasion and EMT, and inducing cell apoptosis. These effects are achieved by the inhibition of ß-catenin signaling. Thus Se-PFPs can be used as potential therapeutic agents in the prevention and treatment of ovarian cancer.