Abstract
Natural polysaccharides exhibit beneficial immune modulatory effects, including immune stimulatory and anti-cancer activities. In this study, we examined the effect of Codium fragile polysaccharide (CFP) on natural killer (NK) cell activation, and its effect on tumor-bearing mice. Intravenous CFP treatment of C57BL/6 mice resulted in the upregulation of CD69, which is a marker associated with NK cell activation. In addition, intracellular levels of interferon (IFN)-γ and the cytotoxic mediators perforin and granzyme B were markedly increased in response to the CFP treatment of splenic NK cells. IFN-γ production by NK cells was directly induced by CFP, whereas the upregulation of CD69 and cytotoxic mediators required IL-12. Finally, intraperitoneal treatment with CFP prevented CT-26 (murine carcinoma) tumor cell infiltration in the lungs, without significantly reducing the body weight. In addition, treatment with CFP prevented B16 melanoma cell infiltration in the lung of C57BL/6 mice. Moreover, the anti-tumor effect was diminished by the depletion of NK cells. Therefore, these data suggest that CFP may be used as an NK cell stimulator to produce a phenomenon that contributes to anti-cancer immunity.
Keywords:
Codium fragile polysaccharide; anti-cancer effect; cytotoxicity; granzyme B; natural killer cell; perforin.
MeSH terms
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Animals
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Antigens, CD / metabolism
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Antigens, Differentiation, T-Lymphocyte / metabolism
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Antineoplastic Agents / isolation & purification
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Chlorophyta / metabolism*
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Colonic Neoplasms / drug therapy*
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Colonic Neoplasms / immunology
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / pathology
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Granzymes
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Interferon-gamma / metabolism
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Interleukin-12 / metabolism
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Killer Cells, Natural / drug effects*
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism
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Lectins, C-Type / metabolism
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Lymphocyte Activation / drug effects*
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Lymphocytes, Tumor-Infiltrating / drug effects*
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Lymphocytes, Tumor-Infiltrating / immunology
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Lymphocytes, Tumor-Infiltrating / metabolism
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Melanoma, Experimental / drug therapy*
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Melanoma, Experimental / immunology
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Melanoma, Experimental / metabolism
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Melanoma, Experimental / pathology
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Polysaccharides / isolation & purification
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Polysaccharides / pharmacology*
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Pore Forming Cytotoxic Proteins / metabolism
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Spleen / drug effects
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Spleen / immunology
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Spleen / metabolism
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Tumor Microenvironment
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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Antineoplastic Agents
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CD69 antigen
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IFNG protein, mouse
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Lectins, C-Type
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Polysaccharides
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Pore Forming Cytotoxic Proteins
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perforin, mouse
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Interleukin-12
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Interferon-gamma
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Granzymes
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Gzmb protein, mouse