Polysaccharide from Codium fragile Induces Anti-Cancer Immunity by Activating Natural Killer Cells

Mar Drugs. 2020 Dec 8;18(12):626. doi: 10.3390/md18120626.

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

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Chlorophyta / metabolism*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Granzymes
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lectins, C-Type / metabolism
  • Lymphocyte Activation / drug effects*
  • Lymphocytes, Tumor-Infiltrating / drug effects*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology*
  • Pore Forming Cytotoxic Proteins / metabolism
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / metabolism
  • Tumor Microenvironment

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Antineoplastic Agents
  • CD69 antigen
  • IFNG protein, mouse
  • Lectins, C-Type
  • Polysaccharides
  • Pore Forming Cytotoxic Proteins
  • perforin, mouse
  • Interleukin-12
  • Interferon-gamma
  • Granzymes
  • Gzmb protein, mouse