Protein bound polysaccharides PSK and PSP have been isolated from distinct strains of mushrooms. These compounds are chemically similar and have a molecular mass of about 100 kDa. The polysaccharide component is made up of monosaccharides with α-(1-4) and β-(1-3) glucosidic linkages, while aspartic and glutamic acids predominate in the peptide component of these compounds. PSK and PSP differ mainly in the presence of fucose in PSK and rhamnose and arabinose in PSP. PSK and PSP are classified as biological response modifiers that stimulate T-cell activation and induce IFN-γ and IL-2 production. The biologic activity is characterized by their ability to increase white blood cell counts, IL-2 production and delayed-type hypersensitivity reactions. In addition, these polysaccharides have been shown to inhibit the growth of tumor cell lines and have in vivo antitumor activity.
The antitumor activity has been evaluated in Japan for prevention of esophageal, gastric, and lung cancer in humans with promising results. In phase II and phase III trials in China, PSP significantly enhanced immune status in 70 to 97% of patients with cancers of the stomach, esophagus, lung, ovary, and cervix. In these studies, PSK and PSP increased the number of immune cells and facilitated dendritic and cytotoxic T-cell infiltration of tumors. The polysaccharides were well-tolerated and compatible with chemotherapy and radiation therapy.
The mechanism of action of these polymers is not clear. Studies have suggested that in treatment of mice with PSK, the PSK binds to and inhibits the immunosuppressive cytokine transforming growth factor beta. PSK and PSP were also found to enhance superoxide dismutase (SOD) activity in mice. Tumor-bearing mice that were treated with the polysaccharides showed decreased tumor growth and increased SOD activity in this tissue. Since SOD is believed to protect cells against superoxide radical-mediated damage it is believed that these polysaccharides ameliorated disease by increasing the activity of this enzyme.
The effect of PSK treatment on neutrophil activity in vivo has been studied and suggests that the activation of this cell type may be responsible in part for efficacy in the treatment of experimental cancers. Animals receiving PSK had increased neutrophil levels with concomitant target cell toxicity and a marked decrease in size and number of lung metastatic foci. This was associated with an increase in chemotactic factors produced by neutrophils.
Source: Clinical Microbological Reviews
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