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Antitumor activity of polymorphonuclear leukocytes activated by a beta-1,3-D-glucan
1Chemotherapy Division, Chiba Cancer Center Research Institute, Japan.
Abstract:
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.
Insights
Beta-1,3-D-glucan (TAK-N) from Alcaligenes faecalis stimulates mouse polymorphonuclear leukocytes (PMN) to exhibit antitumor activity against sarcoma 180 cells. This TAK-N-induced PMN cytotoxicity, mediated by H2O2, shows significant in vivo antitumor effects, prolonging survival time.
Area of Science:
- Immunology
- Biochemistry
- Oncology
Background:
- Polymorphonuclear leukocytes (PMN) play a role in immune responses.
- Beta-1,3-D-glucans are known for their immunomodulatory properties.
- Investigating novel antitumor agents is crucial for cancer therapy.
Purpose of the Study:
- To evaluate the antitumor activity of beta-1,3-D-glucan (TAK-N) and its derivative (CM-TAK) on mouse PMN.
- To elucidate the mechanism of TAK-N-induced cytotoxicity.
- To assess the in vivo efficacy of TAK-N against sarcoma 180 tumors.
Main Methods:
- In vitro cytotoxicity assays using PMN and sarcoma 180 cells.
- Assessment of hydrogen peroxide (H2O2) production.
- In vivo studies involving tumor-bearing mice and intraperitoneal injections.
- Survival analysis of treated mice.
Main Results:
- TAK-N, but not CM-TAK, induced significant PMN cytotoxicity against sarcoma 180 cells in vitro.
- TAK-N-induced cytotoxicity was mediated by H2O2 production, as evidenced by catalase inhibition.
- Intraperitoneal administration of TAK-N increased peritoneal PMN and macrophages.
- Peritoneal PMN from TAK-N-treated mice exhibited cytotoxicity, and TAK-N treatment prolonged survival in tumor-bearing mice.
Conclusions:
- TAK-N effectively stimulates PMN to exert antitumor activity against sarcoma 180 cells.
- The antitumor effect of TAK-N appears to be primarily mediated by PMN activation and H2O2 production.
- TAK-N demonstrates potential as an immunotherapeutic agent for cancer treatment.