Department of Anatomy, Faculty of Medicine, Chinese University of Hong Kong, Shatin.
Abstract
Polysaccharopeptide (PSP) is a substance produced by an edible mushroom, Coriolus versicolor which has been claimed to possess antitumor activity. However, neither tumoricidal activity nor cytotoxicity was observed when five tumor cell lines and mouse peritoneal macrophages were cultured in vitro in the presence of 2.5-10 micrograms/ml PSP. An increase in the production of reactive nitrogen intermediates, reactive oxygen intermediates (superoxide anions) and tumor necrosis factor was measured in peritoneal macrophages collected from inbred C57 mice which had received PSP in the drinking water for 2 weeks. Northern blot analysis also demonstrated that PSP activated the transcription of tumor necrosis factor gene in these cells, indicating that PSP exerted an immunomodulatory effect on the defensive cells.
Third Department of Internal Medicine, Asahikawa Medical College, Japan.
Abstract
Granulocyte-colony-stimulating factor (G-CSF), granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) were used in combination with PSK, a protein-bound polysaccharide extracted from mycelium of Coriolus versicolor (strain CM101), in myelosuppressed mice. The myelosuppression model consisted of BDF1 mice who received 150 mg/kg 5-fluorouracil (5-FU) intravenously. The peripheral blood leukocyte count during the recovery stage was significantly increased when these cytokines were administered with PSK compared to when the cytokines were used individually. In vitro colony assay revealed that the combination of PSK and any of GM-CSF, IL-3 or stem cell factor (SCF) showed a greater increase in colony numbers than when these materials were administered individually, although G-CSF did not show a synergistic effect with PSK. When bone marrow cells were obtained from mice which had been given PSK or IL-3, the colony assays were made in the presence of PSK or IL-3 in vitro. The greatest increase in the numbers was observed in colonies of the cultured group in the presence of IL-3 after the PSK priming. However, the colony formation potential of PSK was not inhibited by addition of anti-SCF antibody. The above results indicate that the combined administration of PSK with G-CSF, GM-CSF or IL-3 increased the hematological recovery of myelosuppressed mice. Moreover, the phase at which PSK has effects on hematopoietic cells seems to be at a more immature level than with IL-3. The combined administration of PSK and the above cytokines may improve myelosuppression after chemotherapy in patients with malignancy.
Molecular Biology Laboratory, Kitasato University School of Medicine, Kanagawa, Japan.
Abstract
The protein-bound polysaccharide of Coriolus versicolor QUEL (PS_K) expresses superoxide dismutase (SOD) mimicking activity. Examination was made of the effects of PS-K on cancer cell lines following administration of the anti-cancer drug cisdiaminedichloroplatinum (cisplatin). Cell proliferation of each cell line was inhibited markedly by cisplatin from 0.5 to 5 micrograms/0.5 ml per well. Fifty percent of the inhibitory concentration (IC50) was 0.33 micrograms/0.5 ml per well in NRK-49F and human ovarian cancer cells, and 1.5 micrograms/0.5 ml per well in H4-II-E. PS-K 50 micrograms/0.5 ml per well prevented cytotoxicity due to cisplatin toward NRK-49F, but enhanced the cytotoxicity on H4-II-E and human ovarian cancer cells. Increase in lipid peroxide and decrease in SOD activity were observed following an IC50 dose of cisplatin. With PS-K 50 micrograms/0.5 ml per well, all the above were augmented in H4-II-E and ovarian cancer cells, but diminished in NRK-49F cell line. PS-K may have effect on cancer patients through its combining with cisplatin.
Molecular Biology Laboratory, Kitasato University School of Medicine, Kanagawa, Japan.
Abstract
The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the mimetic activity of superoxide dismutase (SOD). Human cancer patients usually suffer from oxidative stress (OS). Examination was made to determine the capacity of this drug with SOD mimetic activity for relieving OS. Rats transplanted with Walker 256 fibrosarcoma showed OS on day 12. After confirming high levels of OS on day 13, PS-K50 mg/kg was intraperitoneally administered, and prompt decrease in O2-release from RBC was noted. The drug ceased to have any effect 24 hours following the first inoculation. Average OS in human cancer patients was found twice that in healthy persons. In human cancer patients perorally administered PS-K3.0 g/day, OS decreased to the normal level one day after the initial administration. Plasma lipid peroxide (LPO) in cancer patients treated with PS-K for 28 days increased and withdrawal of the drug led to decreased LPO.
Molecular Biology Laboratory, Kotasato University School of Medicine, Kanagawa, Japan.
Abstract
The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the mimicking activity of superoxide dismutase (SOD). Examination was made of the suppressive effects of PS-K on cancer cell lines cultured in vitro. The SOD activity of LLC-WRC-256 (Walker 256 fibrosarcoma) cell lines was less than that of NRK-49F (rat normal kidney fibroblast), H4-II-E (rat hepatoma) and H4-II-E-C3 (rat hepatoma) cell lines. This activity in Walker 256 fibrosarcoma cells increased by 3.6 times and H2O2 concentration, by 2.56 times by PS-K 500 micrograms/ml. Cell proliferation was consequently suppressed and living cells decreased to less than 50% of the cells cultured without PS-K. Catalase and glutathione peroxidase activity changed little by PS-K. The sensitivity of cancer cells to PS-K can be predetermined based on SOD activity in tumor tissue.
Molecular Biology Laboratory, Kitasato University School of Medicine, Kanagawa, Japan.
Abstract
The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses superoxide dismutase (SOD) mimicking activity. Examination was made of the suppressive effects of PS-K on cancer cell lines cultured in vitro. SOD activity of incorporated PS-K was 5.88 u/mg in LLC-WRC-256 (Walker 256 fibrosarcoma) cells and 4.73 u/mg in NRK-49F (rat normal kidney fibroblast) cells. SOD activity in both cell types was enhanced about 7-8 times that of the original PS-K. PS-K was not incorporated into H4-11-E or H4-11-E-C3 (rat hepatoma) cells. SOD activity of 1 mg/ml PS-K incubated with cell homogenates of LLC-WRC-256 cells for 6 hours increased from 0.68 u/mg to 1.35 u/mg. SOD activity of PS-K 1 mg/ml in 0.05 M phosphate buffer incubated with 50 microM NADPH increased from 0.68 u/mg. The consumption of NADPH at the same concentration was confirmed spectrophotometically by incubation with PS-K. The mechanism for the enhancement of SOD activity associated with PS-K is considered to be collaboration with NADPH as an electron donor in the cytoplasm of cancer cells whose SOD and coupling enzyme activities are significantly lower than in normal cells.
Kureha Chemical Ind. Co., Ltd., Biomedical Research Laboratories, Tokyo, Japan.
Abstract
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.
Kureha Chemical Ind. Co., Ltd., Biomedical Research Laboratories, Tokyo, Japan.
Abstract
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.
Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong.
Abstract
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.
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.