A protein-bound polysaccharide from mycelia of Coriolus versicolor PS-K, clinically used as an immunomodulator, has been shown to restore the decreased cellular immune response and to exhibit host-mediated antitumor activity. In this experiment, PS-K was found to increase serum complement level in guinea pig and in human without malignancy, when hemolytic assay of complement was performed using sensitized sheep erythrocytes for the classical pathway activity and unsensitized rabbit erythrocytes for the alternative pathway activity. Assay of complement components revealed increase in C3 level in guinea pig, but no significant changes in C1q, C4, C3, properdin, C3 activator, and C1-inhibitor in human, while C5 and C9 were depressed. Conversion of beta 1C to beta 1A was observed in the 7th day’s plasma of these patients by crossed immunoelectrophoresis. Biosynthesis of guinea pig C3 was accelerated by administration of PS-K, but that of C4 was not affected. These evidences suggested that PS-K might potentiate immune response of the host by elevating serum complement level, in addition to the activation of the complement system.
Pulp and Paper Research Institute of Canada, Point Claire, Quebec, Canada H9R 3J9.
Abstract
Screening fifteen strains of white-rot fungi for their ability to decolorize combined bleached kraft effluent showed that Coriolus versicolor in liquid culture removed over 60% of the color of the effluent within six days in the presence of sucrose. Treatment of the same effluent with this fungus, immobilized in beads of calcium alginate gel, resulted in 80% decolorization after three days in the presence of sucrose. Caustic extraction E(1) effluent was also decolorized by the immobilized fungus. Decolorization was achieved more rapidly at pH 5.0 than at pH 7.0. Recycled beads could remove color efficiently and repeatedly in the presence of air but not under anaerobic conditions.
Pulp and Paper Research Institute of Canada, 570 St. John’s Boulevard, Pointe Claire, Quebec, Canada H9R 3J9.
Abstract
Effluent from the caustic extraction stage of a bleach plant is highly colored due to the presence of dissolved products from lignin chlorination and oxidation. Color removal from the effluent by hydrogen peroxide at neutral pH was catalyzed by addition of horseradish peroxidase. The catalysis with peroxidase (20 mg/L) was observed over a wide range of peroxide concentrations (0.1mM-500mM), but the largest effect was between 1mM and 100mM. The pH optimum for catalysis was around 5.0, while the basal rate of noncatalyzed peroxide color removal simply increased with pH within the range tested (3-10). Peroxidase catalysis at pH 7.6 reached a maximum at 40 degrees C in 4 h assays with 10mM peroxide, and disappeared above 60 degrees C. Compared with mycelial color removal by Coriolus versicolor, the rate of color removal by peroxide plus peroxidase was initially faster (first 4 h), but the extent of color removal after 48 h was higher with the fungal treatment. Further addition of peroxidase to the enzyme-treated effluent did not produce additional catalysis. Thus, the peroxide/peroxidase system did not fully represent the metabolic route used by the fungus.
A polysaccharide preparation isolated from Coriolus versicolor (Fr.) Quél. of Basidiomycetes (PSK) predominantly consists of glucan and approximately 25% tightly bound protein. PSK was effective against various allogeneic and syngeneic animal tumors and has been given orally to cancer patients. Various suppressed or enhanced immune responses of tumor-bearing animals were restored to normal levels by the administration of PSK in the tumor models tested. The killer T cell activity was augmented in tumor-bearing mice by intraperitoneal or oral administration of PSK, and there was correlation between the PSK associated antitumor effect and the killer T cell activity. It was found that PSK competed with immunosuppressive substances isolated from tumor-bearing mice and that the intestinal immune system appeared to be modulated by oral administration of PSK. After oral administration of 14C- or 35S-labeled PSK to normal rats, it was found that small or large molecular substances appeared in the serum depending on the time elapsed after administration, an indication that large molecular size products were from the digestive tract.
To elucidate the effects of PSK, a protein-bound polysaccharide from Coriolus versicolor, on gene expression in tumor cells, we prepared cDNA clone libraries from PSK-treated and untreated cells of a rat ascites hepatoma line, AH66, which was previously shown to be susceptible to the antitumor action of this compound. Two PSK-induced and one suppressed cDNA clones were selected from these libraries by using a differential colony hybridization and RNA blot hybridization. PSK was thus shown to have a direct effect on the transcription and consequently on the translation of tumor cells.
Research Section of Lignin Chemistry, Wood Research Institute, Kyoto University, Uji, Kyoto 611, Japan.
Abstract
4-Ethoxy-3-methoxyphenylglycerol-gamma-formyl ester (compound IV) was identified as a degradation product of both 4-ethoxy-3-methoxyphenylglycerol-beta-syringaldehyde ether (compound I) and 4-ethoxy-3-methoxyphenylglycerol-beta-2,6-dimethoxyphenyl ether (compound II) by a ligninolytic culture of Coriolus versicolor. An isotopic experiment with a C-labeled compound (compound II’) indicated that the formyl group of compound IV was derived from the beta-phenoxyl group of beta-O-4 dimer as an aromatic ring cleavage fragment. However, compound IV was not formed from 4-ethoxy-3-methoxyphenylglycerol-beta-guaiacyl ether (compound III). gamma-Formyl arylglycerol (compound IV) could be a precursor of 4-ethoxy-3-methoxyphenylglycerol (compound VI), because 3-(4-ethoxy-3-methoxyphenyl)-1-formyloxy propane (compound VII) was cleaved to give 3-(4-ethoxy-3-methoxyphenyl)-1-propanol (compound VIII) by C. versicolor. 4-Ethoxy-3-methoxyphenylglycerol-beta,gamma-cyclic carbonate (compound V), previously found as a degradation product of compound III by Phanerochaete chrysosporium (T. Umezawa, and T. Higuchi, FEBS Lett., 25:123-126, 1985), was also identified from the cultures with compound I, II, and III and degraded to give the arylglycerol (compound VI). An isotopic experiment with C-labeled compounds II’ and III’ indicated that the carbonate carbon of compound V was derived from the beta-phenoxyl groups of beta-O-4 substructure.
Centro de Investigaciones Biológicas, CSIC, Velázquez, Madrid, Spain.
Abstract
The autolysis and production of some extracellular enzymes by Coriolus versicolor was studied in submerged cultures. After 48 days of incubation the fungus lost 31% of its maximum dry weight. 1.3-beta-glucanase was excreted at the beginning of autolysis and proteases were present during the course of the experiment. On the other hand, laccase was produced in very small amount in the first days of incubation, reaching the maximum activity at the 8th-day of autolysis.
PSK is a protein-bound polysaccharide prepared from cultured mycelium of Coriolus versicolor. The effects of PSK on immunologic responsiveness were investigated in C3H/He mice bearing syngeneic X5563 tumor. The results were as follows. elayed foot pad reaction and antibody-forming capacity to sheep erythrocytes were depressed in tumor bearing mice, and such depression was prevented by oral or intraperitoneal administration of PSK. In vitro cytotoxic activity of splenic lymphocytes against the tumor was augmented by PSK administration. Antitumor effect was augmented by combination of PSK and X-irradiation. Delayed foot pad reaction to sheep erythrocytes was suppressed in normal C3H/He mice given immunosuppressive substance obtained from tumor-bearing mice, and the depressed reaction recovered to the normal level following PSK administration. These results show that PSK is effective in the syngeneic murine tumor system.
PSK is a protein-bound polysaccharide prepared from cultured mycelium of Coriolus versicolor. The appearance of an immunosuppressive effect in sera of tumor-bearing mice and its elimination by oral administration of PSK were investigated using an in vitro assay of blastoid transformation of normal spleen cells in response to PHA. (1) An inhibitory effect appeared in sera of X5563 plasmacytoma-bearing mice, while a facilitating effect was noted in sera of MH134 hepatoma- and MM 102 mammary tumor-bearing mice. (2) The presence of both an inhibitory and a facilitating factor was shown by Sephacryl gel fractionation. (3) Oral administration of PSK resulted in the elimination of the inhibitory effect from sera of X5563-bearing mice. The facilitating effect of sera from MH134-bearing mice was augmented by PSK administration, but that in sera from MM102-bearing mice was not influenced by such treatment. The summarized effects of these factors may be expressed as various types of effects in serum and PSK may be effective in the elimination of a suppressive factor from such sera.
PSK is a protein-bound polysaccharide prepared from cultured mycelium of the Basidiomycete Coriolus versicolor. Effects of PSK on the immunologic responsiveness in tumor-bearing animals were investigated using syngeneic or allogeneic tumors in mice (Lewis lung carcinoma, B16 melanoma, Meth A fibrosarcoma, adenocarcinoma 755, X5563 plasmacytoma, colon 26, MOPC 31C myeloma, sarcoma 180 and Ehrlich carcinoma), rats (BC47 bladder carcinoma, Walker 256 sarcoma and AH7974 hepatoma), hamsters (HA-1T tumor and RPMI 1846 melanoma), guinea pigs (line-10 hepatoma) and rabbit (VX2 and VX7 tumor). Oral or intraperitoneal administration of PSK restored the depressed delayed hypersensitivity against sheep erythrocytes to a normal level in these tumor-host systems. Also, oral administration of PSK lowered the activity of immunosuppressive substances in the serum of tumor-bearing animals. These results suggest that PSK exhibits antitumor effects by restoring the depressed immunologic responsiveness in tumor-bearing animals.