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 Biochemistry, Faculty of Medicine, Chinese University of Hong Kong, China.
Abstract
1. Coumarins, flavonoids and polysaccharopeptide were tested for antibacterial activity. 2. The bacteria used for this study included clinical isolates of Staphylococcus aureus, Shigella flexneri, Salmonella typhi, Escherichia coli and Pseudomonas aeruginosa. 3. Most of the coumarins tested failed to inhibit the bacteria at 25 mg/l. Edultin at 128 mg/l inhibited 4 of the 8 P. aeruginosa strains and 1 of the S. aureus strains tested. O-acetylcolumbianetin and imperatorin did not inhibit any isolate, even at 128 mg/l. 4. When tested at the dose of 128 mg/l, the flavonoids (rutin, naringin and baicalin) inhibited 25% or less of P. aeruginosa and only baicalin was active against S. aureus. 5. Arbutin and 4-(beta-D-glucopyranosyloxyl)-benzaldehyde inhibited 3 of the 8 P. aeruginosa strains when tested at 128 mg/l. 6. Polysaccharopeptide from the fungus Coriolus versicolor failed to inhibit any P. aeruginosa or S. aureus strain at 128 mg/l.
Research and Development Division, Kikkoman Corporation, Chiba Pref., Japan.
Abstract
Complementary DNA encoding pyranose oxidase (PROD) was cloned and sequenced for the first time from Coriolus versicolor. The nucleotide sequence revealed an open reading frame encoding a polypeptide composed of 623 amino acid residues. Compared with the experimentally determined N-terminal sequence of the PROD from C. versicolor. 38 amino acids from the N-terminus of the protein appeared to be eliminated during protein maturation. The cDNA was successfully expressed under the control of lacUV5 promoter in Escherichia coli at 25 degrees C, which will be beneficial in industrial production.
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.
Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
Abstract
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 Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abstract
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 Hydrospheric Environmental Protection, National Institute for Resources and Environment, Tsukuba, Ibaraki, Japan. iimura@nire.go.jp
Abstract
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.
Abstract
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.
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.
Laboratory of Wood Chemistry, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Japan.
Abstract
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.