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.
Highlights
Compared to chemically synthesized agents, natural polysaccharides exhibit beneficial activities, such as antibacterial, antiviral, and anti-cancer effects in humans and animals [1,2]
The expression of CD69, which is a specific marker of lymphocyte activation, was found to be significantly increased in splenic natural killer (NK) cells upon C. fragile polysaccharide (CFP) treatment (Figure 1b)
CD69 expression observed in splenic NK cells upon CFP treatment was highest 18 h after injection, and rapidly reduced
Summary
Compared to chemically synthesized agents, natural polysaccharides exhibit beneficial activities, such as antibacterial, antiviral, and anti-cancer effects in humans and animals [1,2]. Natural marine polysaccharides, including fucoidan, ascophyllan, and carrageenan, promote immune cell-mediated anti-cancer effects [3,4]. Codium fragile is a green alga that is abundantly found in China, Japan, and Korea This alga contains the following: Polysaccharides (44.1–80.5%); sulfates (3.2–22.2%); proteins (3.0–15.7%); and uronic acids (1.1–4.2%) [5,6]. Fraction 2 of the C. fragile polysaccharide (CFP) enhanced the cytotoxic activities of natural killer (NK) cells in vivo [9]. NK cells are involved in innate immunity [11]. Our previous studies revealed that CFP induces the activation of mouse DCs in vivo and NK cells in vitro. We examined whether CFP activates NK cells and enhances anti-cancer immunity in mice
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