Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
Polysaccharide peptide (PSP) is a protein-bound polysaccharide extracted from an edible mushroom, Coriolus versicolor. Effects of PSP (2g/kg/day) on cyclophosphamide (CPA, 40 mg/kg/2 days)-induced immunosuppression were investigated by determining lymphocyte proliferation, Natural killer (NK) cell formation, IgG and IL-2 concentration, WBC count and the weight of organs after rats were treated with or without CPA in the presence or absence of PSP. The results demonstrated that PSP possessed immunopotentiating effect, being effective in restoring CPA-induced immunosuppression such as depressed lymphocyte proliferation, Natural Killer cell function, production on white blood cell and the growth of spleen and thymus in rats as well as in increasing both IgG and IL-2 production on which CPA did not have significant effects under the conditions of our experiments. PSP can partly restore CPA-induced immunosuppression. Based on our findings and the data accumulated so far, it was suggested that PSP should be considered as an useful adjuvant especially combined with CPA or other chemotherapy in clinical treatment of cancer patients. The mechanism by which PSP restores the immunosuppression induced by CPA is unclear.
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, New Territories. firstname.lastname@example.org
Polysaccharopeptide (PSP) isolated from the edible mushroom Coriolus versicolor was tested for its potential as an anti-human immunodeficiency virus type 1 (HIV-1) compound in a series of in vitro assays. It demonstrated inhibition of the interaction between HIV-1 gp 120 and immobilized CD4 receptor (IC50 = 150 microg/ml), potent inhibition of recombinant HIV-1 reverse transcriptase (IC50 = 6.25 microg/ml), and inhibited a glycohydrolase enzyme associated with viral glycosylation. These properties, coupled with its high solubility in water, heat-stability and low cytotoxicity, make it a useful compound for further studies on its possible use as an anti-viral agent in vivo.
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
A retrospective analysis of postoperative chemotherapy had shown the continuous administration of UFT, an oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4, to be effective for poorly differentiated gastric cancer. We therefore sought to determine prospectively the effective dose of postoperative chemotherapy with UFT for patients with poorly differentiated gastric cancer following a curative resection. We determined the effect of the combined intravenous administration of mitomycin C (MMC) and oral treatment with protein-bound polysaccharide Kreha (PSK), extracted from the basidiomycete Coriolus versicolor, and UFT at a dose of either 8 mg/kg or 12 mg/kg daily for 1 year. A total of 224 patients with poorly differentiated stage II-IV gastric cancer were entered into this study after undergoing a curative resection. No differences were observed between the two treatment groups in terms of prognostic factors, the toxicity rate or the doses of the drugs prescribed, other than UFT. The higher dose of UFT in maintenance therapy led to a decrease in the recurrence rate (P < 0.05), and increases in disease-free survival and cause-specific survival (P < 0.05). UFT at 12 mg/kg in postoperative chemotherapy was thus found- to improve the postoperative results with no increase in toxicity for poorly differentiated gastric cancer, and is also cost-effective for outpatients.
Department of Forest Products, Kyushu University, Higashi-ku, Fukuoka, Japan.
The degradation of thiodiglycol (I) and benzyl sulfide (II) was attempted using Coriolus versicolor and Tyromyces palustris to investigate the potential ability of basidiomycetes to degrade Yperite (bis(2-chloroethyl) sulfide), a mass-produced and stored chemical warfare agent. I was very rapidly degraded by both fungi. The metabolic pathway of II was elucidated, showing that the initial step was the hydrolytic cleavage of the thioether bond to yield benzyl alcohol and benzyl mercaptan. Benzyl alcohol was further oxidized and finally mineralized. Benzyl mercaptan is reversibly converted to benzyl disulfide and also converted to benzyl alcohol. Finally, the effective degradation of bis(2-bromoethyl) sulfide strongly suggests that basidiomycete would be a potential tool for Yperite degradation.
Department of Hydrospheric Environmental Protection, National Institute for Resources and Environment, Tsukuba, Ibaraki, Japan. email@example.com
White-rot fungus Coriolus versicolor, a ligninolytic basidiomycete, has been studied because of its ability to degrade hazardous chemicals. In this study, we searched for genes that are induced by a hazardous chemical using the mRNA differential-display technique and C. versicolor IFO30340 that has been exposed to pentachlorophenol (PCP). Five cDNA fragments were cloned and the DNA sequences of two fragments were analyzed in further detail. The clones corresponded to novel genes that have not previously been identified in C. versicolor. One of the cDNAs exhibited strong sequence homology to the gene for an enolase and the other exhibited homology to a heat shock protein. The expression of the two genes was up-regulated in PCP-treated C. versicolor.
Departments of Biochemistry and Anatomy, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
1. Coriolus versicolor polysaccharopeptide has been reported to exert immunomodulatory and antitumor actions. The present study showed that it exhibits analgesic activity in the hot-plate test upon intraperitoneal administration to ICR mice. 2. It did not affect ovarian steroidogenesis, ovulation and midterm gestation in mice. It did not exert an adverse effect on mouse embryonic development either, as evidenced by the lack of an effect on somite number, axial length and the incidence of abnormalities in heartbeat, yolk sac circulation, optic vesicle, otic vesicle, shape of body axis, forelimb buds, branchial apparatus, cranial neural tube and head size. 3. Its analgesic activity would add to its attribute as an immunomodulatory and antitumor drug.
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
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.
Laboratory of Wood Chemistry, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Japan.
A second laccase gene, CVLG1, was isolated from Coriolus versicolor. CVLGI encodes a precursor protein of 526 amino acids which contains a 23-amino acid signal sequence, and the coding region is interrupted by 11 introns. The number of potential N-glycosylation sites in this product is 12 and the greatest among that of polyporales laccases. Moreover, this protein shares about 70% homology with other polyporales laccases. Genomic Southern analysis showed that C. versicolor laccases are encoded by more than four genes including CVLG1 and a transposed allele of this gene.
Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Moscow Region, Russia.
Extracellular laccases from submerged cultures of Coriolus versicolor BKM F-116, Panus tigrinus 8/18, Phlebia radiata 79 (ATCC 64658), Phlebia tremellosa 77-51 and from cultures of Pa. tigrinus 8/18, Ph. radiata 79 and Agaricus bisporus D-649 grown on wheat straw (solid-state fermentation) were purified. All enzymes from submerged cultures had a blue colour and characteristic absorption and EPR spectra. Laccases from the solid-state cultures were yellow-brown and had no typical blue oxidase spectra and also showed atypical EPR spectra. Comparison of N-terminal amino acid sequences of purified laccases showed high homology between blue and yellow-brown laccase forms. Formation of yellow laccases as a result of binding of lignin-derived molecules by enzyme protein is proposed.
Department of Biochemistry, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
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.