A polysaccharide preparation isolated from Coriolus versicolor (Fr.) Quél. of Basidiomycetes (PSK) predominantly consists of glucan and approximately 25% tightly bound protein. PSK was effective against various allogeneic and syngeneic animal tumors and has been given orally to cancer patients. Various suppressed or enhanced immune responses of tumor-bearing animals were restored to normal levels by the administration of PSK in the tumor models tested. The killer T cell activity was augmented in tumor-bearing mice by intraperitoneal or oral administration of PSK, and there was correlation between the PSK associated antitumor effect and the killer T cell activity. It was found that PSK competed with immunosuppressive substances isolated from tumor-bearing mice and that the intestinal immune system appeared to be modulated by oral administration of PSK. After oral administration of 14C- or 35S-labeled PSK to normal rats, it was found that small or large molecular substances appeared in the serum depending on the time elapsed after administration, an indication that large molecular size products were from the digestive tract.
To elucidate the effects of PSK, a protein-bound polysaccharide from Coriolus versicolor, on gene expression in tumor cells, we prepared cDNA clone libraries from PSK-treated and untreated cells of a rat ascites hepatoma line, AH66, which was previously shown to be susceptible to the antitumor action of this compound. Two PSK-induced and one suppressed cDNA clones were selected from these libraries by using a differential colony hybridization and RNA blot hybridization. PSK was thus shown to have a direct effect on the transcription and consequently on the translation of tumor cells.
Research Section of Lignin Chemistry, Wood Research Institute, Kyoto University, Uji, Kyoto 611, Japan.
Abstract
4-Ethoxy-3-methoxyphenylglycerol-gamma-formyl ester (compound IV) was identified as a degradation product of both 4-ethoxy-3-methoxyphenylglycerol-beta-syringaldehyde ether (compound I) and 4-ethoxy-3-methoxyphenylglycerol-beta-2,6-dimethoxyphenyl ether (compound II) by a ligninolytic culture of Coriolus versicolor. An isotopic experiment with a C-labeled compound (compound II’) indicated that the formyl group of compound IV was derived from the beta-phenoxyl group of beta-O-4 dimer as an aromatic ring cleavage fragment. However, compound IV was not formed from 4-ethoxy-3-methoxyphenylglycerol-beta-guaiacyl ether (compound III). gamma-Formyl arylglycerol (compound IV) could be a precursor of 4-ethoxy-3-methoxyphenylglycerol (compound VI), because 3-(4-ethoxy-3-methoxyphenyl)-1-formyloxy propane (compound VII) was cleaved to give 3-(4-ethoxy-3-methoxyphenyl)-1-propanol (compound VIII) by C. versicolor. 4-Ethoxy-3-methoxyphenylglycerol-beta,gamma-cyclic carbonate (compound V), previously found as a degradation product of compound III by Phanerochaete chrysosporium (T. Umezawa, and T. Higuchi, FEBS Lett., 25:123-126, 1985), was also identified from the cultures with compound I, II, and III and degraded to give the arylglycerol (compound VI). An isotopic experiment with C-labeled compounds II’ and III’ indicated that the carbonate carbon of compound V was derived from the beta-phenoxyl groups of beta-O-4 substructure.
Centro de Investigaciones Biológicas, CSIC, Velázquez, Madrid, Spain.
Abstract
The autolysis and production of some extracellular enzymes by Coriolus versicolor was studied in submerged cultures. After 48 days of incubation the fungus lost 31% of its maximum dry weight. 1.3-beta-glucanase was excreted at the beginning of autolysis and proteases were present during the course of the experiment. On the other hand, laccase was produced in very small amount in the first days of incubation, reaching the maximum activity at the 8th-day of autolysis.
PSK is a protein-bound polysaccharide prepared from cultured mycelium of Coriolus versicolor. The effects of PSK on immunologic responsiveness were investigated in C3H/He mice bearing syngeneic X5563 tumor. The results were as follows. elayed foot pad reaction and antibody-forming capacity to sheep erythrocytes were depressed in tumor bearing mice, and such depression was prevented by oral or intraperitoneal administration of PSK. In vitro cytotoxic activity of splenic lymphocytes against the tumor was augmented by PSK administration. Antitumor effect was augmented by combination of PSK and X-irradiation. Delayed foot pad reaction to sheep erythrocytes was suppressed in normal C3H/He mice given immunosuppressive substance obtained from tumor-bearing mice, and the depressed reaction recovered to the normal level following PSK administration. These results show that PSK is effective in the syngeneic murine tumor system.
PSK is a protein-bound polysaccharide prepared from cultured mycelium of Coriolus versicolor. The appearance of an immunosuppressive effect in sera of tumor-bearing mice and its elimination by oral administration of PSK were investigated using an in vitro assay of blastoid transformation of normal spleen cells in response to PHA. (1) An inhibitory effect appeared in sera of X5563 plasmacytoma-bearing mice, while a facilitating effect was noted in sera of MH134 hepatoma- and MM 102 mammary tumor-bearing mice. (2) The presence of both an inhibitory and a facilitating factor was shown by Sephacryl gel fractionation. (3) Oral administration of PSK resulted in the elimination of the inhibitory effect from sera of X5563-bearing mice. The facilitating effect of sera from MH134-bearing mice was augmented by PSK administration, but that in sera from MM102-bearing mice was not influenced by such treatment. The summarized effects of these factors may be expressed as various types of effects in serum and PSK may be effective in the elimination of a suppressive factor from such sera.
PSK is a protein-bound polysaccharide prepared from cultured mycelium of the Basidiomycete Coriolus versicolor. Effects of PSK on the immunologic responsiveness in tumor-bearing animals were investigated using syngeneic or allogeneic tumors in mice (Lewis lung carcinoma, B16 melanoma, Meth A fibrosarcoma, adenocarcinoma 755, X5563 plasmacytoma, colon 26, MOPC 31C myeloma, sarcoma 180 and Ehrlich carcinoma), rats (BC47 bladder carcinoma, Walker 256 sarcoma and AH7974 hepatoma), hamsters (HA-1T tumor and RPMI 1846 melanoma), guinea pigs (line-10 hepatoma) and rabbit (VX2 and VX7 tumor). Oral or intraperitoneal administration of PSK restored the depressed delayed hypersensitivity against sheep erythrocytes to a normal level in these tumor-host systems. Also, oral administration of PSK lowered the activity of immunosuppressive substances in the serum of tumor-bearing animals. These results suggest that PSK exhibits antitumor effects by restoring the depressed immunologic responsiveness in tumor-bearing animals.
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Abstract
OK-432, a lyophilized preparation of Streptococcus pyogenes, showed a priming activity for TNF production in mice, associated with an increase of spleen weight. PSK, a protein-bound polysaccharide preparation from Coriolus versicolor, did not show such activity. Both OK-432 and PSK potentiated the TNF production in mice primed with Corynebacterium parvum (CP) and challenged with Escherichia coli endotoxin (LPS). Cytotoxic antitumor agents of 5-fluorouracil (5-FU), cyclophosphamide (CY) and bleomycin (BLM) suppressed TNF production in mice primed with CP and challenged with LPS. TNF production suppressed by 5-FU, CY and BLM was partially restored by the combined treatment with OK-432 or PSK. These results suggest that the administration of cytotoxic antitumor agents suppresses the intrinsic TNF production in cancer patients, and the combined use of immunostimulants such as OK-432 and PSK is advantageous in restoring TNF production suppressed by cytotoxic antitumor agents.
Kureha Chemical Industry Co., Ltd. Biomedical Research Laboratories, Tokyo, Japan.
Abstract
The effect of PSK (Krestine, an anti-tumor drug prepared from Coriolus versicolor) on splenectomized experimental animals was investigated. Splenectomy was performed on both a tumor-free control group and a tumor-bearing group. The administration of PSK on the splenectomized control group significantly increased the immune state of the host. In the case of the tumor-bearing group, administration of PSK resulted in restoration of the immune function as observed in the control group. Recovery of the immunological function was accelerated when tumor-bearing animals were splenectomized at the terminal stage. The results suggest that the immunomodulating effects of PSK developed at the time of the splenectomy resulted in anticancer activity.
August Kirchenstein Institute of Microbiology, Latvian Academy of Sciences, 226067 Riga, Kleisti, Latvian SSR, USSR.
Abstract
A novel two-stage bioreactor has been designed for a combined submerged (SF) and solid substrate fermentation (SSF) of wheat straw. The straw was pretreated with steam, and cellulases from the culture fluid of Trichoderma reesei were adsorbed on it for increased bioconvertibility. SSF was conducted in the top part of the bioreactor by inoculating the straw with a 36-h mycelial culture of T. reesei, or Coriolus versicolor. In the bottom part of the fermenter, Endomycopsis fibuliger was grown in SF. The SF liquor was recirculated through the SSF stage at 24 h intervals to remove glucose and other metabolites that may inhibit growth, and to maintain optimum moisture level and temperature. The removed glucose and other metabolites provided nutrients for the yeast in the SF stage. The combined fermentation resulted in overall higher biomass yield, increased bioconversion, increased cellulase production, and increased digestibility compared with single SSF or SF.