Abstract
Medicinal mushrooms have been used for centuries against cancer and infectious diseases. These positive biological effects of mushrooms are due in part to the indirect action of stimulating immune cells. The objective of the current study is to investigate the possible immunomodulatory effects of mushroom polysaccharides on NK cells against different cancer cells. In this current study, fruiting bodies isolated from cultured Pleurotus ostreatus were extracted and partially purified using DEAE ion-exchange chromatography. The activation action of the collected fractions on Natural Killer cells was quantified against three different cancer cell lines in the presence or absence of human recombinant IL2 using three different activation and co-culture conditions. The possible modes of action of mushroom polysaccharides against cancer cells were evaluated at the cellular and molecular levels. Our results indicate that P. ostreatus polysaccharides induced NK-cells cytotoxic effects against lung and breast cancer cells with the largest effect being against breast cancer cells (81.2%). NK cells activation for cytokine secretion was associated with upregulation of KIR2DL genes while the cytotoxic activation effect of NK cells against cancer cells correlated with NKG2D upregulation and induction of IFNγ and NO production. These cytotoxic effects were enhanced in the presence of IL2. Analysis of the most active partially purified fraction indicates that it is predominantly composed of glucans. These results indicate bioactive 6-linked glucans present in P. ostreatus extracts activate NK-cell cytotoxicity via regulation of activation and induction of IFNγ and NO. These studies establish a positive role for bioactive P. ostreatus polysaccharides in NK-cells activation and induction of an innate immune response against breast and lung cancer cells.
Highlights
Cancer is considered as one of the major human death causes worldwide
Our results indicate that P. ostreatus polysaccharides induced Natural killer (NK)-cells cytotoxic effects against lung and breast cancer cells with the largest effect being against breast cancer cells (81.2%)
Gray) showed abilities to induce immune system activation by its effect on the macrophages, dendritic cells (DCs), and NK cells (Kodama et al, 2003). To further explore this interesting finding, the current study focused on the immune- stimulatory effects of Pleurotus ostreatus polysaccharide fractions on NK cells and the role of cytokine secretion and stimulatory receptors in three NK-cancer cells co-culture models
Summary
Cancer is considered as one of the major human death causes worldwide. Recently, many of anti-cancer therapies are available, including chemo- and immune-therapeutic agents, which are known to give rise to various adverse effects. Mushrooms are known to produce antimicrobial, anti-inflammatory, cardiovascularprotective, antidiabetic, hepatoprotective, and anticancer agents (Nouroz et al, 2016) It is well-established that mushrooms are able to regulate the immune responses by affecting hematopoietic stem cells, lymphocytes, macrophages, T cells, dendritic cells (DCs), and NK cells (Ooi and Liu, 2000). Several mushroom polysaccharides have been established as potent antitumor agents: Lentinan from Lentinula edodes (Chihara et al, 1970), SSG from Sclerotinia sclerotiorum FKL (Suzuki et al, 1988), and Schizophyllan from Schizophyllum commne Fries (Mitani et al, 1982; Daba and Ezeronye, 2003; Hong et al, 2012) These polysaccharides regulate both macrophages and T cells immunomodulatory chemokines and cytokines. Gray) showed abilities to induce immune system activation by its effect on the macrophages, DCs, and NK cells (Kodama et al, 2003)
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