Fucoidan from Durvillaea Antarctica elicits anticancer immunity against lung cancer via natural killer cell activation.

Several polysaccharides extracted from seaweed have immunostimulatory effects. However, active substances from various diverse seaweeds should be identified to determine optimal immune stimulators. The dendritic cell (DC) activation ability of fucoidan extracted from Durvillaea antarctica (FDA) has been verified previously. However, the effect of FDA on the activation of natural killer (NK) cells that can directly kill tumor cells has not been studied. In this study, we investigated the effect of FDA in NK cell activation and examined its therapeutic effect on metastatic lung cancer. Intraperitoneal FDA administration to C57BL/6 mice increased the number of NK cells in the spleen and promoted Ki67 expression in these cells. In addition, FDA treatment upregulated CD69 in NK cells and interferon-γ, perforin, and granzyme B production. Furthermore, FDA-activated NK cells exhibited potent cytotoxicity against TC-1 lung cancer cells. FDA administration to mice attenuated metastatic TC-1 lung cancer growth. Moreover, the FDA-mediated NK cell activation was partially direct and partially DC-mediated. Finally, the therapeutic effect of FDA on metastatic lung cancer was significantly weakened in NK cell-depleted mice. Therefore, these data demonstrated that FDA attenuates lung metastasis growth by activating immune cells including NK cells.