concanavalin-a and Sarcoma-180

Methylglyoxal is a normal metabolite and has the potential to affect a wide variety of cellular processes. In particular, it can act selectively against malignant cells. The study described herein was to investigate whether methylglyoxal can enhance the non-specific immunity of the host against tumor cells. Methylglyoxal increased the number of macrophages in the peritoneal cavity of both normal and tumor-bearing mice. It also elevated the phagocytic capacity of macrophages in both these groups of animals. This activation of macrophages was brought about by increased production of Reactive Oxygen Intermediates (ROIs) and Reactive Nitrogen Intermediates (RNIs). The possible mechanism for the production of ROIs and RNIs can be attributed to stimulation of the respiratory burst enzyme NADPH oxidase and iNOS, respectively. IFN-gamma, which is a regulatory molecule of iNOS pathway also showed an elevated level by methylglyoxal. TNF-alpha, which is an important cytokine for oxygen independent killing by macrophage also increased by methylglyoxal in both tumor-bearing and non tumor-bearing animals. Methylglyoxal also played a role in the proliferation and cytotoxicity of splenic lymphocytes. In short, it can be concluded that methylglyoxal profoundly stimulates the immune system against tumor cells.

Topics: Animals; Antineoplastic Agents; Cell Proliferation; Concanavalin A; Cytotoxicity, Immunologic; Female; Interferon-gamma; Interleukin-12; Lymphocyte Activation; Lymphocytes; Macrophage Activation; Macrophages, Peritoneal; Mice; NADP; Nitric Oxide Synthase Type II; Nitrites; Pyruvaldehyde; Sarcoma 180; Superoxides; Tumor Necrosis Factor-alpha

Calcineurin (CN) is a Ca (2+)/calmodulin-stimulated protein phosphatase. It is a heterodimeric enzyme consisting of a catalytic subunit (CN A) and a Ca2+ -binding regulatory subunit (CN B), which plays an important role in the human immune system. Its regulatory subunit, CN B, on its own, was found to have a remarkable anticancer effect in mice. To clarify the basis of this action the in vivo and in vitro effect of CN B on several types of mice immunocytes was investigated. The phagocytic activity of peritoneal macrophages of both normal mice and mice bearing S 180 solid tumors increased when CN B was injected daily. In vitro examination using a modified MTT assay and an [3H] incorporation assay showed that the cytotoxicity of peritoneal macrophages was increased substantially. CN B also increased the natural killer activity of murine spleen lymphocytes in vivo and in vitro, and synergized with concanavalin A in stimulating their proliferation. Our results indicate that CN B has a significant stimulatory action on the immune system that may partially account for its anticancer activity.

Topics: Animals; Antineoplastic Agents; Calcineurin; Cell Proliferation; Cell Survival; Cells, Cultured; Concanavalin A; Dose-Response Relationship, Drug; Drug Synergism; Killer Cells, Natural; Lymphocyte Subsets; Macrophages, Peritoneal; Male; Mice; Mice, Inbred BALB C; Phagocytosis; Sarcoma 180; Spleen

One of the so-called LC components, the content of which is increased in the serum of PSK (antitumor polysaccharide) treated mice, was purified by repeated ion-exchange column chromatography on DEAE-Sephadex A-50. The purified protein, designated as LC-2, was identified as a variant of mouse transferrin, which is a serum beta 1-globulin having an iron-binding capacity. The absorption spectrum and ultraviolet circular dichroism (CD) curve of LC-2 were identical with those of mouse transferrin. The molecular weight, isoelectric point and amino acid composition of LC-2 were in good agreement with the results obtained previously for mouse transferrin. However, the carbohydrate content of LC-2 was different from that of mouse transferrin. This protein restored the depressed spleen cell response of tumor-bearing mice to concanavalin A (Con A) and promoted the metabolism of proteose-peptone induced peritoneal macrophages obtained from tumor-bearing mice. Furthermore, it had weak but definite antitumor activity against Sarcoma 180 cells in vivo.

Topics: Animals; Antibiotics, Antineoplastic; Chromatography, Gas; Circular Dichroism; Concanavalin A; Electrophoresis, Polyacrylamide Gel; Female; Glucose; Hemopexin; Hydrolysis; Isoelectric Point; Lymphocyte Activation; Macrophages; Mice; Mice, Inbred DBA; Mice, Inbred ICR; Molecular Weight; Proteoglycans; Sarcoma 180; Sarcoma, Experimental; Spectrophotometry, Ultraviolet; Transferrin

Concanavalin A (Con A) and trypsin inhibitor isolated from Acacia confusa were covalently linked with N-succinimidyl-3-(2-pyridyldithio)propionate. Con A-A. confusa trypsin inhibitor (ACTI) conjugate covalently bound (Con A-ACTI) retained about 42% of the trypsin inhibitory activity present in the native ACTI and had a higher hemagglutinating activity than did the native Con A. Con A-ACTI had a greater resistance to tryptic digestion than did the mixture of Con A and ACTI. The conjugate entered sarcoma 180 tumor cells, whereas the free ACTI did not. A single dose of the conjugate injected ip into noninbred N:NIH(S) white mice bearing sarcoma 180 had a remarkable effect of increasing the survival of tumor-bearing mice, while the mixture of an equivalent dose of free Con A and ACTI was not effective.

Topics: Animals; Cell Division; Cell Line; Cell Membrane Permeability; Chromatography, Gel; Concanavalin A; Electrophoresis, Polyacrylamide Gel; Hemagglutination Tests; Mice; Peptide Hydrolases; Protein Binding; Sarcoma 180; Trypsin Inhibitors

We isolated an antitumor glucan (HA beta-glucan) from the neutral polysaccharide fraction (A3) of a hot-water extract of the edible mushroom P. ostreatus (Fr.) Quél. Purification was accomplished by extractions with 20% sodium chloride solution saturated with thymol and by precipitations with ethanol from dimethyl sulfoxide solution. The glucan showed marked antitumor activity at a dose of 0.1 mg/kg. It is a highly branched (1----3)-beta-glucan having an average structure represented by a pentasaccharide segment consisting of one nonreducing terminal, one 3,6-di-O-substituted, and three 3-mono-O-substituted beta-D-glucopyranosyl residues. This structure was confirmed by examining 13C-n.m.r. spectra taken at 75.46 MHz.

Topics: Animals; Antineoplastic Agents, Phytogenic; Basidiomycota; Chromatography, Gas; Concanavalin A; Female; Gas Chromatography-Mass Spectrometry; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred ICR; Plant Lectins; Plants, Medicinal; Polysaccharides; Sarcoma 180

Phytohemagglutinin (PHA) and concanavalin A (Con A) were used as probes to detect changes in the cell surface of Dalton's lymphoma, sarcoma-180 and Ehrlich's carcinoma after short in vitro exposure to acriflavine. Dye-treated cells showed enhancement of agglutination both by PHA and Con A, and such enhancement was found to be dependent on the time of exposure and concentration of acriflavine. However, PHA-induced percent agglutination seemed to be much higher than that of Con A among the 3 cell types. There were also marked differences among the 3 cell types in order of their sensitivity to lectin-mediated agglutination. The strength of the response was greater in lymphoma to both PHA and Con A than that of sarcoma-180 and carcinoma cells, which appeared to be most resistant. Acriflavine, which is known as an intercalative agent with DNA, induces cell surface changes by promoting lectin-mediated cellular agglutination.

Topics: Acriflavine; Agglutination; Aminoacridines; Animals; Carcinoma, Ehrlich Tumor; Cell Membrane; Cells, Cultured; Concanavalin A; Lymphoma; Male; Mice; Phytohemagglutinins; Sarcoma 180

Methotrexate and chlorambucil, each covalently linked to either abrus agglutinin, abrin, ricinus agglutinin, ricin, or concanavalin A, were prepared. A single dose of the derivative injected ip into sarcoma 180-bearing noninbred N:NIH(S) white mice resulted in prolongation of the survival time and was more effective than an equivalent dose of free drug and lectin. Drug-lectin also showed a higher inhibitory effect on the DNA biosynthesis of the tumor cell than did an equivalent dose of the free drug and lectin.

Topics: Abrin; Animals; Chlorambucil; Concanavalin A; DNA, Neoplasm; Lectins; Male; Methotrexate; Mice; Ricin; Sarcoma 180

Adriamycin increases (a) the rate of agglutination of Sarcoma 180 cells by concanavalin A after brief exposure of 2-3 h and (b) membrane fluidity as measured by ESR within 30 min of exposure at concentrations of the anthracycline of 10(-7)-10(-5) M. The effect of adriamycin on agglutination is not due to an increase in the number of surface receptors for concanavalin A, since the extent of binding of the lectin is not altered by adriamycin and no change occurs in the rate of occupancy of the concanavalin A binding sites by the lectin in cells treated with the antibiotic. The order parameter, a measurement of membrane fluidity, decreases in cells exposed to adriamycin and is dose-related. The results indicate that adriamycin can induce changes in the surface membrane of Sarcoma 180 cells within a brief period of exposure to a low but cytotoxic level of this agent.

Topics: Agglutination; Animals; Cell Membrane; Concanavalin A; Doxorubicin; Kinetics; Membrane Fluidity; Mice; Receptors, Concanavalin A; Sarcoma 180

Topics: Agglutination; Agglutination Tests; Animals; Cell Membrane; Concanavalin A; Erythrocytes; Humans; Methylmannosides; Mice; Rabbits; Rats; Sarcoma 180; Surface Properties

Topics: Animals; Cell Membrane; Concanavalin A; Depression, Chemical; Glycoproteins; Lectins; Mannose; Mice; Neoplasm Proteins; Ricin; Sarcoma 180; Thioguanine; Time Factors

Topics: Animals; Antigen-Antibody Reactions; Concanavalin A; Cytotoxicity, Immunologic; Immunity, Cellular; Immunosuppression Therapy; Isoantibodies; Isoantigens; Mice; Sarcoma 180; T-Lymphocytes; Thymus Gland

Topics: Animals; Cells, Cultured; Concanavalin A; Doxorubicin; Mice; Sarcoma 180; Surface Properties; Time Factors

Topics: Animals; Antineoplastic Agents; Cell Membrane; Cells, Cultured; Concanavalin A; Female; Lectins; Mice; Plant Lectins; Sarcoma 180; Time Factors; Triticum

Topics: Agglutination; Animals; Ascitic Fluid; Binding Sites; Binding, Competitive; Cell Line; Cells, Cultured; Concanavalin A; Dose-Response Relationship, Drug; Methylglucosides; Mice; Sarcoma 180; Spectrophotometry; Time Factors; Tritium; Trypsin