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November 2010

Suppression of in vivo tumor-induced angiogenesis by the protein-bound polysaccharide PSK.

The anti-angiogenic effects of an antitumor protein-bound polysaccharide, PSK, obtained from cultured mycelia of Coriolus versicolor in basidiomycetes were examined by the mouse dorsal air sac assay. PSK suppressed the mouse hepatoma MH134-induced angiogenesis when assessed by morphological and biochemical examinations. This finding suggested that the anti-metastatic effect of PSK is attributed to the suppression of tumor-induced angiogenesis.[…]

Enhancement of the antitumor effect by the concurrent use of a monoclonal antibody and the protein-bound polysaccharide PSK in mice bearing a human cancer cell line.

The antitumor effects of a monoclonal antibody against a human cancer cell line and a protein-bound polysaccharide, PSK, obtained from cultured mycelia of Coriolus versicolor in basidiomycetes were examined. The IgG2a monoclonal antibody against the human colon cancer cell line colo 205 induced in vitro antibody-dependent macrophage-mediated cytotoxicity against the cancer cells, but only slightly suppressed the in vivo growth of the cancer cells. Concurrent use of PSK with the antibody enhanced the in vitro antibody-dependent macrophage-mediated cytotoxicity as well as the in vivo antitumor activity. These findings suggest that the combined use of a monoclonal antibody and PSK, which have different modes of action, may be useful in the treatment of cancer.[…]

In vitro bleaching of hardwood kraft pulp by extracellular enzymes excreted from white rot fungi in a cultivation system using a membrane filter.

To clarify the role of excreted extracellular enzymes during long-term incubation in a pulp biobleaching system with white rot fungi, we developed a cultivation system in which a membrane filter is used; this membrane filter can prevent direct contact between hyphae and kraft pulp, but allows extracellular enzymes to attack the kraft pulp. Phanerochaete sordida YK-624 brightened the pulp 21.4 points to 54.0% brightness after a 5-day in vitro treatment; this value was significantly higher than the values obtained with Phanerochaete chrysosporium and Coriolus versicolor after a 7-day treatment. Our results indicate that cell-free, membrane-filtered components from the in vitro bleaching system are capable of delignifying unbleached kraft pulp. Obvious candidates for filterable reagents capable of delignifying and bleaching kraft pulp are peroxidase and phenoloxidase proteins. The level of secreted manganese peroxidase activity in the filterable components was substantial during strain YK-624 in vitro bleaching. A positive correlation between the level of manganese peroxidase and brightening of the pulp was observed.[…]

Effect of Residual Lignin Type and Amount on Bleaching of Kraft Pulp by Trametes versicolor.

The white rot fungus Trametes (Coriolus) versicolor can delignify and brighten unbleached hardwood kraft pulp within a few days, but softwood kraft pulps require longer treatment. To determine the contributions of higher residual lignin contents (kappa numbers) and structural differences in lignins to the recalcitrance of softwood kraft pulps to biobleaching, we tested softwood and hardwood pulps cooked to the same kappa numbers, 26 and 12. A low-lignin-content (overcooked) softwood pulp resisted delignification by T. versicolor, but a high-lignin-content (lightly cooked) hardwood pulp was delignified at the same rate as a normal softwood pulp. Thus, the longer time taken by T. versicolor to brighten softwood kraft pulp than hardwood pulp results from the higher residual lignin content of the softwood pulp; possible differences in the structures of the residual lignins are important only when the lignin becomes highly condensed. Under the conditions used in this study, when an improved fungal inoculum was used, six different softwood pulps were all substantially brightened by T. versicolor. Softwood pulps whose lignin contents were decreased by extended modified continuous cooking or oxygen delignification to kappa numbers as low as 15 were delignified by T. versicolor at the same rate as normal softwood pulp. More intensive O(2) delignification, like overcooking, decreased the susceptibility of the residual lignin in the pulps to degradation by T. versicolor.[…]

Effect of polysaccharide peptide (PSP) on glutathione and protection against paracetamol-induced hepatotoxicity in the rat.

The protective effects of polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, on paracetamol-induced hepatotoxicity was investigated in this study. The effect of PSP on hepatic glutathione status was also studied. PSP (300 mg/kg, i.p.) caused a 40% depletion of hepatic reduced glutathione (GSH) with a concomitant 50% increase in oxidized glutathione (GSSG), thus producing a 3-fold increase in the GSSG/GSH ratio. The PSP-induced GSH depletion itself had no hepatotoxic effects. PSP protected against paracetamol-induced hepatotoxicity by decreasing the paracetamol-induced elevation of serum glutamic-pyruvic transaminase (SGPT) activity from 511 +/- 71 U/ml to 187 +/- 58 U/ml (controls without paracetamol 105 +/- 4 U/ml) and serum glutamic-oxaloacetic transaminase (SGOT) activity from 462 +/- 63 to 152 +/- 48 U/ml (controls without paracetamol 54 +/- 6 U/ml). PSP did not reverse the depletion of total glutathione (GSH+GSSG) by the toxic dose of paracetamol. The GSSG/GSH ratio, which is a measure of oxidative stress, was significantly (p < 0.05) decreased when PSP was coadministered with paracetamol. PSP dose-dependently decreased the covalent binding of [14C]-paracetamol to microsomal proteins in vitro. When PSP was given to rats subchronically for 7 days (300 mg/kg/day, i.p.), the subsequent microsomes obtained also showed a 25% decrease in covalent binding to [14C]-paracetamol, suggesting that PSP interacted with the microsomal proteins rather than the chemically reactive metabolite of paracetamol. The changes in the binding affinity and capacity of the microsomal proteins by PSP may be related to its ability to alter the redox potential as indicated by the effects of PSP on the GSSG/GSH status.[…]

Immunomodulatory and antitumor activities of a polysaccharide-peptide complex from a mycelial culture of Tricholoma sp., a local edible mushroom.

A polysaccharide-peptide complex (PSPC) with immunomodulatory and antitumor activities was obtained from a submerged mycelial culture of Tricholoma sp., a local edible mushroom. The polysaccharide-peptide complex exhibited a molecular weight of 17 K in gel filtration and a single band after SDS-polyacrylamide gel electrophoresis. It was characterized by non-adsorption on both DEAE-Sepharose CL-6B and CM-cellulose. It could activate the macrophages, stimulate the proliferation of T-cells, and inhibit the growth of sarcoma 180 in mice. It possessed more potent immunomodulatory and antitumor activities than Coriolus versicolor polysaccharopeptide (PSP) and deserves to be studied as a potential agent for immunomodulation and cancer therapy.[…]

Prolongation of the survival period with the biological response modifier PSK in rats bearing N-methyl-N-nitrosourea-induced mammary gland tumors.

The antitumor effects of a protein-bound polysaccharide (PSK) obtained from cultured mycelia of Coriolus versicolor in basidiomycetes on mammary gland tumors produced in Sprague-Dawley rats by the intravenous injection of N-methyl-N-nitrosourea were investigated. PSK prolonged the survival period of tumor-bearing rats significantly, when given at the dose of 250 mg/kg twice a week for 3 weeks after the tumor reached 100 mm2 in size (p = 0.011 by log rank test and p = 0.023 by generalized Wilcoxon test). These findings suggest that PSK is effective in the prolongation of the survival period in the rat autochthonous tumor model, acting at the growth stage of the tumor during carcinogenesis.[…]

Biological treatment of distillery waste for pollution-remediation.

The biological treatment of spent wash from molasses distilleries was investigated. Analysis of raw spent wash showed it to be a recalcitrant waste, with a high COD of 85,170 mg/l and containing inhibitory phenolic compounds. Reverse phase thin layer chromatography identified gallic and vanillic acid present in spent wash. The fungi Geotrichum candidum, Coriolus versicolor, Phanerochaete chrysosporium and Mycelia sterilia were screened for their ability to decolourize spent wash and to reduce the COD level. A 10 day pretreatment with Geotrichum candidum at 30 degrees C resulted in reducing the COD by 53.17% and total phenols by 47.82%, enabling other bioremediating organisms to grow. Coriolus versicolor immobilized in a packed-bed reactor reduced the COD of spent wash by a further 50.3%, giving an overall reduction in COD of 77% to 15,780 mg/l. A small amount of decolourization was achieved (4.2%), although the spent wash was still coloured. Present studies are encouraging and indicate that it is possible to bioremediate spent wash using a multi-stage treatment process involving an initial pretreatment step with Geotrichum candidum.[…]

Laccase component of the Ceriporiopsis subvermispora lignin-degrading system.

Laccase activity in the lignin-degrading fungus Ceriporiopsis subvermispora was associated with several proteins in the broth of cultures grown in a defined medium. Activity was not increased significantly by adding 2,5-xylidine or supplemental copper to the medium. Higher activity, associated with two major isoenzymes, developed in cultures grown on a wheat bran medium. These two isoenzymes were purified to homogeneity. L1 and L2 had isoelectric points of 3.4 and 4.8, molecular masses of 71 and 68 kDa, and approximate carbohydrate contents of 15 and 10%, respectively. Data indicated 4 copper atoms per mol. L1 and L2 had overlapping pH optima in the range of 3 to 5, depending on the substrate, and exhibited half-lives of 120 and 50 min at 60 degrees C. They were strongly inhibited by sodium azide and thioglycolic acid but not by hydroxylamine or EDTA. The isoenzymes oxidized 1,2,4,5-tetramethoxybenzene but not other methoxybenzene congeners. A variety of usual laccase substrates, including lignin-related phenols and ABTS [2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)], were also oxidized. Kinetic parameters were similar to those of the laccases of Coriolus versicolor. The N-terminal amino acid sequence (20 residues for L1) showed significant homology to those of laccases of other white rot basidiomycetes but not to those of the laccases of Agaricus bisporus or Neurospora crassa.[…]

Antimetastatic effects of PSK (Krestin), a protein-bound polysaccharide obtained from basidiomycetes: an overview.

PSK, a protein-bound polysaccharide obtained from cultured mycelia of Coriolus versicolor in basidiomycetes, is a biological response modifier, diverse operations of which include an antitumor action. We have previously reviewed recent research which had demonstrated that in animals, PSK has a preventive effect on chemical carcinogen-induced, radiation-induced, and spontaneously developed carcinogenesis (Kobayashi et al., Cancer Epidemiol., Biomarkers & Prev., 2: 271-276, 1993). We now focus on the effects of PSK once the progression of carcinogenesis has begun, and review what is now known of the preventive action of PSK on cancer metastasis. Recent research reports that PSK suppresses pulmonary metastasis of methylcholanthrene-induced sarcomas, human prostate cancer DU145M, and lymphatic metastasis of mouse leukemia P388, and that it has prolonged the survival period in spontaneous metastasis models. PSK also suppresses the metastasis of rat hepatoma AH60C, mouse colon cancer colon 26, and mouse leukemia RL male 1 in artificial metastasis models. PSK influences the steps of cancer metastasis in a number of ways: (a) by suppression of intravasation through the inhibition of tumor invasion, adhesion and production of cell matrix-degrading enzymes; (b) by suppression of tumor cell attachment to endothelial cells through the inhibition of tumor cell-induced platelet aggregation; (c) by suppression of tumor cell migration after extravasation through the inhibition of tumor cell motility; and (d) by suppression of tumor growth after extravasation through the inhibition of angiogenesis, the modulation of cytokine production, and the augmentation of effector cell functions. In addition, PSK has suppressed the malignant progression of mouse tumor cells through superoxide trapping.(ABSTRACT TRUNCATED AT 250 WORDS)[…]