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.
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.
Laboratory of Neurobiology, Suzhou Medical College, China.
Abstract
AIM: The nervous mechanism of the immune potentiating effect of Coriolus versicolor polysaccharides peptides (PSP) was studied in Wistar rats.
METHODS: The unit discharge of the mediobasal hypothalamus (MBH) neurons was recorded extracellularly and the lymphocyte proliferation was measured.
RESULTS: PSP 1 g.kg-1 ig for 5 d increased the T-lymphocytes and promoted T-lymphocyte proliferation in spleen and peripheral blood. This promoting effect of PSP was blocked by MBH lesion. PSP increased the discharge frequency of MBH neurons, but no increase in discharge frequency was observed after treatment of PSP plus immune inhibitor, cyclosporin A.
CONCLUSION: MBH is involved in the immune-potentiating effect of PSP.
Research Laboratory of Free Radical Medicine, First Military Medical University, Guangzhou, China.
Abstract
In previous works, it has been evidenced that lipoperoxidative injury to macrophages caused by oxidatively modified low-density lipoprotein (O-LDL) plays an important role in foam cell formation, and that PSK, a protein bound polysaccharide extracted from the class Basidiomycetes Coriolus Versicolor, can protect macrophages from lipoperoxidative injury induced by tert-butyl hydroperoxide (tbOOH). In this paper PSK protection of macrophages from lipoperoxide (LPO) accumulation and foam cell formation caused by O-LDL and its action mechanism were further studied. The LPO accumulation was determined by using ACAS 570. Dynamic assay of the LPO level in eight single cells after adding O-LDL or determination of the average LPO content in a lot of cells incubated in advance with O-LDL for 12 h, both indicated that O-LDL might induce LPO accumulation in macrophages and the effects of O-LDL could be prevented by PSK. O-LDL might cause the changes of morphological structure in macrophages and the transformation of macrophages into foam cells, and the effects could also be prevented by PSK. The determination of selenium-dependent glutathione peroxidase (SeGSHPx) activities and mRNA contents of macrophages and changes of SeGSHPx activity and mRNA content after incubation with tbOOH showed that PSK might increase the SeGSHPx activity of macrophage and the enhanced SeGSHPx activity may occur at the level of gene transcription.
Department of Radiation Medicine, Loma Linda University/Independent Order of Foresters Cancer Research Laboratory, CA 92350, USA.
Abstract
The purpose of the present study was to evaluate the therapeutic efficacy of locally administered low-dose interleukin-2 (IL-2) and a polysaccharopeptide (PSP) derived from Cariolous versicolor in a herpes virus Type 2-transformed murine tumor (H238) model and to determine possible mechanisms of action. BALB/c mice were inoculated subcutaneously (s.c.) with H238 tumor cells and randomized into groups: a) no tumor and no treatment control, b) tumor and no treatment control, c) tumor + IL-2 at 0 to 4 days, d) tumor + PSP at 0 to 10 days, e) tumor + IL-2 at 0 to 4 days + PSP at 0 to 10 days, and f) tumor + IL-2 at 15 to 19 days + PSP at 15 to 25 days. The IL-2 was administered s.c. at 2 x 10(4) i.u./mouse/injection; PSP was given s.c. at 2 mg/mouse/injection. No obvious toxicity was noted during the treatments. IL-2 and, to a lesser extent, PSP significantly slowed (p < 0.05) tumor progression when given alone immediately after tumor cell injection. The combination of the two modalities did not significantly enhance the antitumor effect of IL-2 alone. However, mice receiving both agents had IL-2 in the plasma, their tumors expressed low levels of transforming growth factor-beta, and their splenocyte response to mitogenic stimulation was significantly higher than in untreated controls. Changes in blood leukocyte populations and splenic oxidative burst capacity were associated with tumor presence, but not with the type of treatment. In vitro assays showed that both IL-2 and PSP can suppress the uptake of 3H-thymidine by tumor cells and that the effect is more pronounced whent the agents are used in combination. These results indicate that IL-2 and PSP can slow progression of H238 tumors and that the mechanisms of action may be related to their direct cytotoxic effects, as well to their immunomodulatory properties.
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Abstract
OK-432 (picibanil), a streptococcal preparation, has a strong biological response modifier (BRM) function and is expected to produce clinical improvement and prolongation of survival in treated cancer patients in Japan. We were interested in whether OK-432 augments estrogen receptor (ER) levels in breast cancer. To investigate the effect of the BRMs on cellular growth and the characteristics of ER and progesterone receptors (PgR) in the human breast cancer cell line MCF-7, we used OK-432, Krestin (PSK), a protein-bound polysaccharide extracted from Coriolus versicolor, and lentinan, a fungal branched (1…3)-beta-D-glycan. OK432 and PSK dose dependently inhibited DNA synthesis of MCF-7 cells, and the 50% inhibitory concentrations of OK-432 and PSK were 1.2 KE (klinische Einheit, clinical unit)/ml and 200 micrograms/ml, respectively. Lentinan showed no direct anticancer effect in vitro. We found that OK-432 induced a 2-fold increase in ER levels in MCF-7 cells at 0.005 KE/ml, but not in PgR. Lentinan and low-dose PSK did not change ER or PgR levels, but high-dose PSK decreased ER and PgR. We also studied the combined effect of OK-432 and antiestrogens, tamoxifen (TAM) and DP-TAT-59. The combined treatment with OK-432 and TAM showed an additive inhibitory effect on MCF-7 cells. These results suggest that OK-432 may augment the therapeutic effect of TAM in breast cancer.
Department of Biochemistry, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Abstract
1. Protein-bound polysaccharides, designated as PSK and PSP, have been isolated from the CM-101 strain and the COV-1 strain, respectively, of the mushroom Coriolus versicolor. This article aims at summarizing existing research findings about PSP since information on PSK is well documented. 2. PSP possesses a molecular weight of approximately 100 kDa. Glutamic and aspartic acids are abundant in its polypeptide component, whereas its polysaccharide component is made up of monosaccharides with alpha-1,4 and beta-1,3 glucosidic linkages. The presence of fucose in PSK and rhamnose and arabinose in PSP distinguishes the two protein-bound polysaccharides, which are otherwise chemically similar. 3. PSP is classified as a biological response modifier. It induces, in experimental animals, increased gamma-interferon production, interleukin-2 production, and T-cell proliferation. It also counteracts the depressive effect of cyclophosphamide on white blood cell count, interleukin-2 production and delayed-type hypersensitivity reaction. Its antiproliferative activity against tumor cell lines and in vivo antitumor activity have been demonstrated. A small peptide with a molecular weight of 16-18 kDa originating from PSP has been produced with antiproliferative and antitumor activities. 4. PSP administered to patients with esophageal cancer, gastric cancer and lung cancer, and who are undergoing radiotherapy or chemotherapy, helps alleviate symptoms and prevents the decline in immune status.
Nutritional Immunology Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Abstract
Decline in immune response is a well-documented age-associated biological change. Protein-bound polysaccharides (PSP) are biological response modifiers and have been shown to have immunoenhancing and antitumor effects. This study was conducted to examine the effect of dietary supplementation with PSP-containing extract derived from mycelia of Coriolus versicolor on in vitro and in vivo indices of immune function of young and old mice. Young (5 mo) and old (23 mo) C57BL/6NIA mice were fed purified diets containing 0, 0.1, 0.5 or 1.0% PSP for 1 mo at which time indices of immune function were measured. PSP supplementation had no significant effect on mitogenic response to concanavalin A (Con A), phytohemagglutinin (PHA) or lipopolysaccharide (LPS), or on production of interleukin (IL)-1, IL-2, IL- 4 and prostaglandin E2 (PGE2). Of the in vivo indices of immune function tested, old mice fed 1.0% PSP had significantly higher delayed-type hypersensitivity (DTH) response than those fed 0% PSP. No significant effect of PSP was observed on the DTH response of young mice. The antibody response to sheep red blood cells was not significantly influenced by PSP in young or old mice. These results suggest that PSP-containing extract from mycelia of Coriolus versicolor might have a modest immunoenhancing effect in aged mice, but not in young mice.
PMID: 9446842 [PubMed – indexed for MEDLINE]Free Article