Department of Biology, Chinese University of Hong Kong, Shatin.
Abstract
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.
Kureha Chemical Ind. Co., Ltd., Biomedical Research Laboratories, Tokyo, Japan.
Abstract
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.
Biotechnology Research Group, School of Applied Biological & Chemical Sciences, University of Ulster, Coleraine, Northern Ireland, UK.
Abstract
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.
Institute for Microbial and Biochemical Technology, U.S. Department of Agriculture, Madison, Wisconsin 53705, USA.
Abstract
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.
PMID: 7793921 [PubMed – indexed for MEDLINE]PMCID: PMC167352Free PMC Article
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)
PMID: 7606203 [PubMed – indexed for MEDLINE]Free Article
Department of Pharmacology, Chinese University of Hong Kong, Shatin.
Abstract
The effect of polysaccharide peptide (PSP), an immunomodulator isolated from Coriolus versicolor COV-1, on the disposition of paracetamol was investigated in the rat. PSP (100 and 200 mg/kg, i.v.) was administered 30 min before a moderate dose (100 mg/kg, i.v.) of paracetamol was given. Plasma and bile concentrations of paracetamol, paracetamol glucuronide and paracetamol sulphate were measured by high performance liquid chromatography. The pharmacokinetics of paracetamol (100 mg/kg) alone was consistent with those reported previously, using a one-compartment model. PSP (200 mg/kg) significantly (P < 0.05) increased the clearance (controls, 19.06 +/- 2.74 ml/min/kg: PSP treated, 26.22 +/- 0.84 ml/min/kg) and volume of distribution (controls, 1.35 +/- 0.11 l/kg: PSP treated, 1.61 +/- 0.04 l/kg) of paracetamol by 37% and 21%, respectively. These changes were associated with concomitant increases in the glucuronide and sulphate metabolites in plasma, with significant increases in the Cmax and Tmax for both metabolites. The biliary excretion rate of paracetamol glucuronide and paracetamol sulphate were also measured. The Cmax values of paracetamol sulphate were significantly (P < 0.01) increased by 2.4-fold from 907.8 +/- 157.7 micrograms/ml (controls) to 3061 +/- 331 micrograms/ml after PSP treatment. The lower dose of PSP (100 mg/kg) had no significant effect on the disposition of paracetamol in this study, which agreed with previous reports that a low dose of PSP (100-200 mg/kg, i.p.) was less effective in the protection against paracetamol-induced hepatotoxicity. The time course of the increase in paracetamol sulphate in plasma and bile in this study coincided with the transient perturbation of glutathione (GSH) turnover by a similar dose range of PSP previously described, such that more cysteine was available for oxidation to inorganic sulphate. This increase in sulphate conjugation by PSP would, in part, contribute to the increase in disposition of paracetamol and may be related to the ability of PSP to decrease the covalent binding of paracetamol to microsomal proteins previously reported. Further studies are necessary to understand the mechanism(s) involved in the PSP-induced increases in paracetamol glucuronide and paracetamol sulphate formation and biliary excretion.
Department of Medical Oncology, Singapore General Hospital, Singapore.
Abstract
Polysaccharide-peptide (PSP) is a protein-bound complex carbohydrate derived from mycelia extract of Chinese fungus coriolus versicolor, or better known as Yun-Zhi. It has been shown to inhibit growth of cultured tumour cells, and it prevents cytotoxic-induced bone marrow suppression. An animal study was conducted with 24 Wistar rats to verify the myeloprotective effect of PSP. The rats were divided into two equal groups: group A (given cyclophosphamide [CTX]) and group B (given PSP and CTX). The body weights were similar in both groups of rats. In phase 1, all rats were given intravenous CTX 75 mg/kg. In addition, B rats received PSP 20 mg/day orally from 7 days before CTX to 14 days after CTX. Phase 2 was carried out two weeks after full recovery from CTX-induced cytopenia. The CTX was decreased to 60 mg/kg, and the group B rats received an increased dose of PSP 1.2 g/day for the same 21 days. In both phases, the CTX was well tolerated. Nadir white blood cell count was reached on day 4 and all counts recovered by day 10. There was no difference in absolute neutrophil, lymphocyte and platelet counts between groups A and B. We concluded that oral PSP did not prevent CTX-induced cytopenia in rats.
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Abstract
The morphologic changes in PMNs induced by an i.p. injection of PSK, a polysaccharide from the mycelia of Coriolus versicolor, and tumor cells undergoing cell death, were evaluated by immunohistochemical staining and electron microscopy. Male C3H/He mice, 8-10 -weeks old, received an i.p. injection of 125 mg/kg of PSK. Their PMNs were obtained 6 h after the PSK injection by peritoneal lavage. N-CWS (Nocardia rubra cell wall skeleton) was added at the start of the chromium release assay using the MM46 mammary carcinoma cell line, which is syngeneic to C3H/He mice, as target cells. During the cytotoxic assay, the cells were fixed at various time points. The MM46 cells expressed ICAM-1 while the PMNs expressed both ICAM-1 and LFA-1 as determined by immunohistochemical staining and immunoelectron microscopy using anti-ICAM-1 and anti-LFA-1 antibodies. PMNs with ruffle-like microvilli adhered to the MM46 tumor cells 30 min after the addition of N-CWS. Immunoelectron microscopic findings suggested that the adhesion molecules were LFA-1 on the PMNs and ICAM-1 on the MM46 tumor cells, but cell fusion between the PMNs and tumor cells was not observed. The MM46 tumor cells gradually lost their microvilli, which showed cell damage, and died 6-7 h after the addition of the N-CWS. This time course of tumor cell death is compatible with the results of the cytotoxic assay. Pretreatment of PMNs by anti-LFA-1 antibody suppressed 1% lysis of MM46 tumor cells from 90% to 10% (p < 0.01). These data suggest that adhesion molecule on the surface of PMNs such as LFA-1 might play an important role on signal transduction of these PMNs cytotoxic function in this experimental system.
Institute of Radiation Biology, National Tsing-Hua University, Taiwan, China.
Abstract
AIM: To study the restorative effect of Coriolus versicolor polysaccharides (CVP) on spleen injury induced by gamma-ray irradiation in mice.
METHODS: ICR Male mice, 6-8 wk old, were divided at random into 3 groups: A) normal control; B) irradiated with 1 Gy; and C) after 1 Gy irradiation, given CVP 60 mg.kg-1 (ig) daily for 10 d continuously. Body weight (BW), spleen weight (SW), relative SW (RSW), DNA synthesis of splenocytes (DNA-SS), and relative DNA-SS were measured on d 5, 12, 19, 26, and 33 after irradiation.
RESULTS: SW, RSW, DNA-SS, and relative DNA-SS decreased after irradiation. CVP enhanced the recovery of SW, RSW, DNA-SS, and relative DNA-SS inhibited by irradiation.
CONCLUSION: CVP has the restorative effect against spleen injury induced by gamma-ray irradiation in mice.
Department of Pharmacology, Second Military Medical University, Shanghai, China.
Abstract
AIM: To study if Coriolus versicolor polysaccharides (CVP) influence the superoxide dismutase (SOD) activities in mice.
METHODS: Normal, tumor-bearing, and radiated ICR mice were injected ip with CVP daily for 3-15 d. The SOD activity was assayed by epinephrine autoxidation test.
RESULTS: The SOD activities in lymphocytes and thymus were increased by CVP in both the normal mice with or without delayed hypersensitivity (DH). In tumor-bearing mice, CVP exerted not only inhibitory effects on tumor, growth and SOD activity in tumor tissue but also complete or partial restorative effects on the suppressed DH and on the declined SOD activities in lymphocytes, spleen, and thymus. The total SOD and manganese-containing SOD (MnSOD) activities in lymphocytes and thymus were dose-dependently enhanced by CVP (5-20 mg.kg-1) on d 3 after the tumor transplantation. In the mice exposed to 60Co (3 or 6 Gy), DH and SOD activities were dose-dependently decreased. These changes were completely or partly prevented by CVP.
CONCLUSION: CVP exerted the favorable effects on SOD activities in mice. Coriolus versicolor polysaccharides (CVP) exert inhibitory effects on experimental and clinical tumors. These effects are presumed to be mediated mainly by host-defence mechanism, especially immunological responeses. Superoxide dismutase (SOD) plays an important role in protecting cells against superoxide radical (O2-.) damages and over-production of O2-. or SOD abnormities exist in many diseases. The present study was to investigate if the CVP could exert some favorable effects on SOD activities in vivo.