laminaran and Sarcoma-180

We have established a convenient, two-step procedure to solubilize the yeast cell wall (1-->3)-beta-D-glucan using the combination of NaClO oxidation and DMSO extraction. Candida soluble beta-D-glucan (CSBG) was mainly composed of a linear beta-1,3 glucan with a linear beta-1,6-glucan moiety. In this study, we screened for several immunopharmacological activities of CSBG and found the following activities: (1) interleukin-6 synthesis of macrophages in vitro; (2) antagonistic effect for zymosan mediated-tumor necrosis factor synthesis of macrophages; (3) augmentation for lipopolysaccharide mediated tumor necrosis factor and nitrogen oxide syntheses of macrophages; (4) activation of alternative pathway of complement; (5) hematopoietic response on cyclophosphamide induced leukopenia; (6) the antitumor effect on ascites form tumor; (7) Enhanced vascular permeability; (8) priming effect on lipopolysaccharide triggered TNF-alpha synthesis; and (9) adjuvant effect on antibody production. These results strongly suggested that CSBG possessed various immunopharmacological activity.

Topics: Animals; Antibody Formation; Antigen-Presenting Cells; beta-Glucans; Candida; Capillary Permeability; Cell Line; Cyclophosphamide; Glucans; Interleukin-6; Leukocyte Count; Lipopolysaccharides; Mice; Mice, Inbred ICR; Sarcoma 180; Tumor Necrosis Factor-alpha

Sparassis crispa is an edible mushroom recently cultivable in Japan. Polysaccharide fractions were prepared from the cultured S. crispa by repeated extraction with hot water (SCHWE), cold NaOH (SCCA), and then hot NaOH (SCHA). HWE was further separated by 1 volume (SCHWE1v) or 4 volumes (SCHWE4v) of ethanol-precipitable fractions. By chemical, enzymic, and NMR analyses, the primary structures of SCHWE1v, SCCA, and SCHA were 6-branched 1,3-beta-glucan, having one branch in approximately every third mainchain unit. All of these fractions showed antitumor activity to the solid form of Sarcoma 180 in ICR mice with strong vascular dilation and hemorrhage reaction. These fractions also showed enhanced hematopoietic response to cyclophosphamide induced leukopenic mice following intraperitoneal or peroral administration.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Disease Models, Animal; Drug Screening Assays, Antitumor; Glucans; Leukocyte Count; Leukopenia; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred ICR; Polyporales; Polysaccharides; Sarcoma 180; Structure-Activity Relationship

The action of carrageenan (CAR), a representative blocking reagent for phagocytes, on the antitumor effect and tissue distribution of highly branched (1-->3-beta-D-glucan, SSG, was examined. CAR inhibited the antitumor effect of intraperitoneally administered SSG only when applied before inoculation of the tumor, and had little effect when applied after tumor inoculation. A similar result was observed when SSG was administered intralesionally. In contrast, CAR had considerable effect on tissue distribution of i.p. SSG. The differences with respect to the results in normal mice were: 1) the distribution of SSG from the peritoneal cavity to the rest of the body was inhibited, 2) large numbers of peritoneal exudate cells (PEC) were produced and a relatively high concentration of 3H-SSG was found in the PEC fraction 48h after administration of 3H-SSG, 3) one week after administration, 3H-SSG was distributed to throughout the body but the amount of 3H-SSG distributed was lower than in normal mice, 4) a significant amount of 3H-SSG was recovered from ligaments (containing omental milky spots, peritoneum, mesentery and associated fat) in which negligible amounts were found in normal mice. The results suggest that the inhibition of the antitumor effect of SSG by CAR probably results from the prevention of the natural resistance of mice which is related to phagocytic function, and that the distribution of SSG to throughout the body is significantly modulated by CAR.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Carrageenan; Exudates and Transudates; Glucans; Male; Mice; Mice, Inbred ICR; Sarcoma 180; Tissue Distribution

Intraperitoneally or intravenously administered (1-->3)-beta-D-glucan remained in the liver and spleen, for a long time without major structural changes, but the priming activity to lipopolysaccharide (LPS)-triggered tumor necrosis factor-alpha (TNF-alpha) production was reduced more quickly. The relationship between the deposited glucan contents and the antitumor activity was examined by comparing kinetics of the activity using solid form Sarcoma 180 tumor in ICR mice. We used three kinds of soluble glucans, sonifilan (SPG), grifolan (GRN), and SSG, and a particulate glucan, zymosan (ZYM). These were administered 5 weeks before (-5W) the tumor inoculation and the tumor weight was compared 5 weeks after the inoculation. Compared with the activity of those administered at the optimum timing, all of the glucans reduced the activity about 5 fold, although significant activity still remained, especially in the case of SPG. Five weeks after intraperitoneal (SPG, GRN, SSG) or intravenous (ZYM) administration of the glucans, all were found in the liver and spleen in significant quantities. These facts strongly suggested that the activity of the glucan was reduced not only because of chemical/physical degradation but also a certain physiological inactivation mechanism.

Topics: Animals; Antineoplastic Agents; Aspartate Aminotransferases; beta-Glucans; Blood Urea Nitrogen; Glucans; Liver; Male; Mice; Mice, Inbred ICR; Sarcoma 180; Spleen

The antitumor activity of mouse polymorphonuclear leukocyte (PMN) treated with a beta-1,3-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 (TAK-N) and its carboxymethylated derivative (CM-TAK) was investigated in vitro and in vivo. ICR mouse PMN showed strong cytotoxicity against sarcoma 180 cells and inhibition of the growth of the tumor cells in vitro in the presence of TAK-N but not in the presence of CM-TAK. Since the cytotoxicity induced by TAK-N was almost completely inhibited by catalase, it seems to be mediated by H2O2 production by PMN. On the other hand, TAK-N induced no cytotoxicity in macrophages and neither did CM-TAK in PMN or in macrophage. Intraperitoneal injection of TAK-N into ICR mice induced a large number of PMN and macrophages in the peritoneal cavity. The peritoneal exudate PMN which were harvested at 10 to 72 h after TAK-N injection showed cytotoxicity against sarcoma 180 cells, but the peritoneal exudate macrophages did not. Treatment of sarcoma 180 ascites tumor-bearing ICR mice with TAK-N at a dose of 100 mg/kg prolonged significantly the survival time over that of the control. These results indicate that TAK-N induces PMN cytotoxicity against sarcoma 180 cells not only in vitro but also in vivo. The antitumor effect of TAK-N on sarcoma 180 ascites tumor seems to be derived from PMN stimulated with TAK-N.

Topics: Animals; beta-Glucans; Cytotoxicity, Immunologic; Free Radical Scavengers; Glucans; Macrophages; Mice; Mice, Inbred ICR; Neoplasms, Experimental; Neutrophils; Sarcoma 180

The antitumor activity of a highly branched (1----3)-beta-D-glucan, SSG, purified from the liquid culture filtrate of Sclerotinia sclerotiorum IFO 9395 and its several derivatives were treated in ICR mice bearing Sarcoma 180 cells. SSG was effective by both systemic (intraperitoneal and intravenous) and local (intratumoral) administrations on the solid form of Sarcoma 180 in ICR mice and the mice acquired resistance to subsequent inoculation of Sarcoma 180. However, SSG was not effective on the ascites form Sarcoma 180. The pretreatment of ICR mice with carrageenan suppressed the antitumor activity, suggesting the involvement of macrophages on the antitumor activity. Derivatives prepared from SSG by periodate oxidation/borohydride reduction showed antitumor activity, but those obtained after acetylation, carboxymethylation and hydroxyethylation were less active. From these results, it is suggested that SSG is a useful antitumor glucan which modifies biological responses and can be used as a source for some antitumor derivatives.

Topics: Acetylation; Animals; Antineoplastic Agents; Ascomycota; beta-Glucans; Chemical Phenomena; Chemistry; Glucans; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred ICR; Oxidation-Reduction; Sarcoma 180

Topics: Animals; Antineoplastic Agents; Ascomycota; beta-Glucans; Chemical Phenomena; Chemistry; Glucans; Mice; Mice, Inbred ICR; Sarcoma 180

Topics: Alginates; Animals; Carbohydrates; Chemical Fractionation; Chromatography; Electrophoresis; Female; Fucose; Glucans; Leukemia L1210; Mice; Mice, Inbred ICR; Molecular Weight; Neoplasm Transplantation; Neoplasms, Experimental; Polysaccharides; Sarcoma 180; Seaweed

An antitumor polysaccharide, EA3 isolated from a Japanese edible mushroom, Flammulina velutipes (CURT. ex FR.) SING. is composed of D-glucose. Studies to determine its structure were performed by mean of partial acid hydrolysis, acetolysis and the chemical analysis of the complete hydrolysates of the fully methylated polysaccharide. Thus the chemical structure of EA3 was found to be that of a beta-(1 leads to 3)-glucan. Another antitumor polysaccharide (EA5) also isolated from F. velutipes was fractionated on a concanavalin A-Sepharose 4B column. The active antitumor component was further purified by column chromatography on Sephadex G-200. Among the polysaccharides isolated the highest molecular weight polysaccharide (EA501) showed the highest rate of antitumor activity. The component sugar of EA501 were found to be D-glucose 42.3%, D-galactose 17.3%, D-mannose 12.2%, D-xylose 6.7% and L-arabinose 14.7%.

Topics: Agaricales; Animals; Antineoplastic Agents; beta-Glucans; Chemical Phenomena; Chemistry; Chromatography, Affinity; Chromatography, Gas; Chromatography, Gel; Chromatography, Liquid; Female; Glucans; Hydrolysis; Methylation; Mice; Mice, Inbred ICR; Polysaccharides; Sarcoma 180