Immunomodulation and Anti-Cancer Activity of Polysaccharide-Protein Complexes

Abstract

In the last three decades, numerous polysaccharides and polysaccharide-protein complexes have been isolated from mushrooms and used as a source of therapeutic agents. The most promising biopharmacological activities of these biopolymers are their immunomodulation and anti-cancer effects. They are mainly present as glucans with different types of glycosidic linkages such as (1-->3), (1-->6)-beta-glucans and (1-->3)-alpha-glucans, and as true herteroglycans, while others mostly bind to protein residues as polysaccharide-protein complexes. Three antitumor mushroom polysaccharides, i.e. lentinan, schizophyllan and protein-bound polysaccharide (PSK, Krestin), isolated respectively, from Lentinus edodes, Schizophyllum commune and Coriolus versicolor, have become large market items in Japan. Lentinan and schizophyllan are pure beta-glucans, whereas PSK is a protein-bound beta-glucan. A polysaccharide peptide (PSP), isolated from a strain of Coriolus versicolor in China, has also been widely used as an anti-cancer and immunomodulatory agent. Although the mechansim of their antitumor action is still not completely clear, these polysaccharides and polysaccharide-protein complexes are suggested to enhance cell-mediated immune responses in vivo and in vitro and act as biological response modifiers. Potentiation of the host defense system may result in the activation of many kinds of immune cells that are vitally important for the maintenance of homeostasis. Polysaccharides or polysaccharide-protein complexes are considered as multi-cytokine inducers that are able to induce gene expression of vaious immunomodulatory cytokines and cytokine receptors. Some interesting studies focus on investigation of the relationship between their structure and antitumor activity, elucidation of their antitumor mechanism at the molecular level, and improvement of their various biological activities by chemical modifications.

Potentiating Effect of .BETA.-Glucans on Photodynamic Therapy of Implanted Cancer Cells in Mice

“…2 and 3). The antitumor activity of β -glucans is known and has been reported in several studies with fungal (1 3),(1 6)-β -glucan, such as shizophylan, lentinam (Ooi and Liu 2000;Zhang et al 2005), (1 3),(1 6)-β -glucan from yeast (Kiho et al 1998). It can be explained that after implantation of tumor cells naturally elicited antitumor antibodies most probably occur, and they function similarly to exogenous antitumor mAbs by coating tumor cells with iC3b fragments (Hong et al 2004).…”

Immunostimulating Activity by Polysaccharides Isolated from Fruiting Body of Inonotus obliquus

“…Especially, polysaccharides are considered to be one of the major active substances in mushrooms (Dalmo and Bøgwald, 2008). Polysaccharides isolated from mushrooms can have significant effects on the innate and adaptive immune response and therefore have the potential as immunostimulators with wide clinical and medicinal applications (Ooi and Liu, 2000;Tsan and Baochong, 2007).…”

Plant Glycoprotein Modulates the Expression of Interleukin-1βviaInhibition of MAP Kinase in HMC-1 Cells

“…Moreover, several reports have found that ROS can stimulate the production of cytokines as a second messenger via the MAP kinase cascade in activated mast cells. 12,32) To determine the inhibitory effect of DBD glycoprotein on PMACIinduced ROS production, we measured the amounts of intracellular ROS using a fluorogenic tracer in PMACIstimulated HMC-1 cells. As described in ''Results,'' PMACI generated intracellular ROS in 30 min, but DBD glycoprotein suppressed PMACI-induced ROS production via inhibition of DCFH oxidation in the mast cells.…”

“…The biological activities of these glycoproteins have attracted attention in the biochemical and medical areas because of their immunomodulatory and anti-oxidative activities. [12][13][14][15] In a previous study, we found that glycoprotein isolated from DBD (DBD glycoprotein) has an anti-apoptotic effect on radicalinduced cell death due to its strong radical scavenging activity, 16,17) but the role of DBD glycoprotein in mastcell biology is unclear.…”