First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.
Abstract
A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr.) Quel, has been recognized for its host-mediated induction of antitumor and antimicrobial activities in mice. Intravenous administration of PSK, in association with OK-432 (Picibanil), transiently induced endogenous production of a cytotoxic factor (CF) (possibly tumor necrosis factor, TNF) in normal mice. The ability to produce CF depended greatly on both dose and interval between administration of the PSK and OK-432. Although PSK has been reported to contain several active ingredients, unfractionated PSK has been used in almost all experiments performed so far. We recently reported that, of the four subfractions separated by successive filtration through membrane filters, only the highest molecular weight fraction F4 (MW greater than 200 kD) induced significant antimicrobial activity in mice. PSK stimulated the NBT-reducing activity of mouse peritoneal macrophages and the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN). Among the subfractions of PSK, the highest molecular weight fraction F4, and the fraction precipitated at pH 4.0-4.5 (Fr. 4), stimulated macrophage NBT-reducing activity and PMN iodination most. In contrast, natural and chemically modified glucans had little or no stimulating activity. PSK, F4 or Fr. 4 additively or synergistically stimulated TNF-induced cytotoxicity against L-929 cells, differentiation of human myelogenous leukemia cell lines toward monocytes/macrophages, and iodination of human peripheral blood PMN. The active PSK subfractions significantly reduced the down regulation of specific 125I-TNF or 125I-IFN-gamma binding to cellular receptors. These data suggest that (i) immunopotentiation activity of PSK might be ascribed, at least in part, to stimulation of cytokine action and production, and (ii) PSK might have some unique structural features.
Cancer Center, Kyushu University Hospital, Fukuoka, Japan.
Abstract
Effects of the immunomodulator PSK on the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) to 5-fluorouracil (5-FU) were examined in 10 patients with advanced gastric cancer and who had undergone curative resection. PSK is a protein-bound preparation, extracted from Coriolus versicolor and belongs to Basidiomycetes. The 5-FU concentration in the plasma was 0.024 micrograms/ml at 15 min after the intravenous injection of 400 mg of tegafur and the area under the curve of 5-FU was 0.58 micrograms.h/ml. Following administration of PSK, 3 g/day for 8-14 months, there was no change in the plasma level of 5-FU, in any patient. As the clinical dose of PSK had no apparent influence on the metabolism of tegafur to 5-FU, the combination of PSK and tegafur can be prescribed to treat patients with advanced gastric cancer.
Department of Chemical Engineering, Faculty of Engineering, Catholic University of Chile, P.O. Box 6177, Santíago, Chile.
Abstract
Our results show that all of the brown rot fungi tested produce oxalic acid in liquid as well as in semisolid cultures. Gloeophyllum trabeum, which accumulates the lowest amount of oxalic acid during decay of pine holocellulose, showed the highest polysaccharide-depolymerizing activity. Semisolid cultures inoculated with this fungus rapidly converted C-labeled oxalic acid to CO(2) during cellulose depolymerization. The other brown rot fungi also oxidized C-labeled oxalic acid, although less rapidly. In contrast, semisolid cultures inoculated with the white rot fungus Coriolus versicolor did not significantly catabolize the acid and did not depolymerize the holocellulose during decay. Semisolid cultures of G. trabeum amended with desferrioxamine, a specific iron-chelating agent, were unable to lower the degree of polymerization of cellulose or to oxidize C-labeled oxalic acid to the extent or at the rate that control cultures did. These results suggest that both iron and oxalic acid are involved in cellulose depolymerization by brown rot fungi.
First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.
Abstract
When mouse resident peritoneal macrophages were cultured with PSK (Krestin), a protein-bound polysaccharide extracted from Coriolus versicolor, they became enlarged and elongated and expressed higher NBT-reducing activity. PSK stimulated the production of differentiation-inducing factor and cytotoxic factor by the mouse macrophage-like cell line J774.1, and iodination (incorporation of radioactive iodine into an acid-insoluble fraction) and interleukin-1-like factor production by human peripheral blood monocytes. Among four different PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD) was the most potent. Natural and chemically modified glucans had little or no activity. The data suggest that some unique structure of the highest molecular weight fraction of PSK directly stimulates the monocytes/macrophages.
Biomedical Research Laboratories, Kureha Chemical Industry, Co., Ltd., Tokyo, Japan.
Abstract
We investigated the effect of PSK, a protein-bound polysaccharide obtained from Coriolus versicolor of basidiomycetes, on antitumor immunity in tumor-bearing mice. PSK prolonged significantly the life span of C3H/He mice bearing syngeneic plasmacytoma X5563 in a schedule- and dose-dependent manner. PSK was most effective when administered at 100 mg/kg every other day ten times starting from the day after tumor inoculation. The administration of PSK enhanced significantly the cytostatic activity of peritoneal exudate plastic-adherent cells and the cytolytic activity of spleen cells after in vitro incubation with mitomycin C-treated tumor cells. In addition, PSK restored the cytokine-producing capacity of spleen cells suppressed in tumor-bearing mice after in vitro incubation with mitogen. Sera from tumor-bearing mice suppressed the activity of such effector cells as well as the interleukin 2-producing capacity of spleen cells, but sera from PSK-treated tumor-bearing mice prevented this suppression. These results suggest that PSK enhances antitumor immunity by reducing immunosuppressive activity of serum from tumor-bearing mice.
Department of Physiology, University of Hong Kong.
Abstract
A new small polypeptide was isolated from the crude extraction of polysaccharide peptide of Coriolus versicolor (Cov-1) by HPLC and CIEF. It has a smaller molecular weight (10K) compared with that of PSP (100K) and was named small peptide of Coriolus versicolor, SPCV. It was found that SPCV possesses potent cytotoxic effect on human tumor cell lines of HL-60, LS174-T, SMMU-7721, and SCG-7901. The IC50 of SPCV on HL-60 was 30 micrograms/ml. The inhibition rates of leukemia cells and SCG-7901 were significantly higher in SPCV treated group than that in PSP and PSK groups. SPCV also has immunopotentiating effect as it increased WBC and IgG levels. Pretreatment of SPCV for two weeks decreased the incidence of tumor mass in nude mice inoculated with tumor cells.
Molecular Biology Laboratory, Kitasato University School of Medicine, Kanagawa, Japan.
Abstract
The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) has been found to express antioxidant activity as an “ion-radical scavenger” in diamine oxidation reactions. The mode of this expression was examined to determine whether the drug functioned as a simple radical scavenger or mimicked the action of superoxide dismutase (SOD). The latter was confirmed in both enzymatic and nonenzymatic superoxide anion radical (O2-.) producing systems in vitro. The SOD mimetic activity of PS-K was demonstrated by quantitative analysis of hydrogen peroxide as the end product of O2-., its formation being assisted catalytically by SOD or PS-K. Analysis by electron spin resonance also confirmed the SOD mimetic activity of PS-K in a xanthine-xanthine oxidase reaction. Relative SOD activity with PS-K was approximately 1/8,000 in a KO2-O2-.-producing system. The SOD mimetic activity of PS-K resisted treatment by 0.7N HCl, 0.7N NaOH, boiling for 30 minutes in a double water bath, and digestion by pronase. Fractionation according to differences in molecular mass caused no significant increase in relative SOD activity within a certain range of molecular mass, indicating that there is no definite molecule expressing SOD mimetic activity. Tumor-bearing rats and human patients with digestive tract cancer who suffered from oxidative stress were relieved by a single intraperitoneal administration of PS-K or a 1-day peroral prescription.
Pulp and Paper Research Institute of Canada, Pointe Claire, Quebec.
Abstract
Many ligninolytic basidiomycete fungi have been shown to secrete a group of peroxidase isozymes whose sole function appears to be the peroxide-dependent oxidation of manganous [Mn(II)] to manganic [Mn(III)] ions. Manganic chelates and these Mn peroxidases have been implicated as central to the degradation of various natural and synthetic lignins and lignin-containing effluents by white rot (ligninolytic) fungi. Another group of enzymes, the laccases, are commonly secreted by wood-rotting fungi, but are generally regarded as being able to oxidize (and usually polymerize) only phenolic substrates. In this report it is shown that in the presence of appropriate oxidizable phenolic accessory substances or primary substrates, a variety of laccases and peroxidases catalyzing one-electron oxidations can also produce Mn(III) chelates from Mn(II).
PMID: 1622216 [PubMed – indexed for MEDLINE]PMCID: PMC195631
Biomedical Research Laboratories, Kureha Chemical Industry Co. Ltd, Tokyo, Japan.
Abstract
The effect of a protein-bound polysaccharide (PSK) obtained from cultured mycelia of the Basidiomycetes Coriolus versicolor on activities involved in the host defence mechanism of C57BL/6 mice bearing adenocarcinoma 755 was compared with that of live bacille Calmette-Guérin (BCG). Delayed footpad reaction, the activity of splenic natural killer cells and interferon production induced by concanavalin A in splenic cells of healthy mice were little affected by PSK, but in mice bearing tumours PSK prevented the tumour-induced reduction in these activities. Live BCG augmented these activities in healthy mice but had little effect on the reduction of activities induced by a tumor. The immunosuppressive activity of the serum of tumour-bearing mice was reduced by PSK administration; live BCG did not have this effect. The combined use of live BCG and PSK improved these activities in the host, with synergistic increases in the antitumour effect. These results suggest that the combined use of live BCG and PSK, which have different modes of action, may be useful in the treatment of cancer.
Department of Surgery II, Faculty of Medicine, Kyushu University Fukuoka, Japan.
Abstract
We evaluated the effects of chemotherapy given postoperatively with and without immunomodulators on the survival of patients who had undergone resection for gastric cancer. We conducted a retrospective survey of data on 963 Japanese patients treated at our department of surgery between 1965 and 1987. Data related to the duration of postoperative survival were calculated for those who received chemotherapy, i.e. an individualized combination of various agents given with or without the immunomodulators PSK, a protein extract of the fungus Coriolus versicolor, and/or OK-432, a preparation of an attenuated strain of Streptococcus (immunochemotherapy). Postoperative immunochemotherapy was more often prescribed for patients with advanced disease. The survival of patients who received immunochemotherapy was shorter than that of patients who received only chemotherapy. In a subgroup of patients adjusted for disease stage, the survival of those on chemotherapy versus immunochemotherapy did not differ significantly at any stage. For optimal results, a protocol for postoperative immunochemotherapy needs to be designed and investigated prospectively and according to the stage of gastric cancer. The stage III gastric cancers seem amenable to a favorable response.