Suppressive effects of fucoidan-agaricus mix (CUA-fucoidan) on angiogenesis and tumor growth in B16 melanoma-bearing mice

Abstract

Abstract Fucoidan is a series of natural sulfated polysaccharides contained in brown sea algae. In previous studies, we proved that fucoidans derived from Cladosiphon okamuranus and Undaria pinnatifida effectively augmented anti-tumor immunity in combination with an Agaricus blazei mycelium extract. In this study, we evaluated dietary effects of the mixture consist of the two high-molecular weights fucoidan and the agaricus extract (named CUA-fucoidan) on tumor angiogenesis. For that purpose, C57BL/6 mice were subcutaneously injected basement membrane matrix (Geltrex) enclosing 5×104 mitomycin C-treated B16 melanoma cells or 500 ng/mL vascular endothelial growth factor (VEGF), and fed 2% CUA-fucoidan containing diet for 7 days before and after the matrix inoculation. The accumulation of hemoglobin and CD31-positive cells in the B16-enclosed Geltrex was lower in the CUA-fucoidan-fed mice than in the control mice, whereas the hemoglobin contents in the VEGF-enclosed Geltrex were not affected by the CUA-fucoidan feeding. These results suggested that CUA-fucoidan was effective in suppressing tumor angiogenesis, but did not inhibit the physiological action of VEGF. Rather, it was guessed that CUA-fucoidan suppressed VEGF production because the expression of VEGF mRNA was reduced in the matrix resected from CUA-fucoidan-fed mice. In this context, the infiltration of CD206-positive macrophages, which known to produce VEGF, were declined by the CUA-fucoidan feeding. Furthermore, CUA-fucoidan decreased accumulation of Treg in the B16-included Geltrex, and delayed B16 tumor growth. In conclusion, CUA-fucoidan was expected to be effective in inhibition of tumor angiogenesis by improving immunosuppressive tumor microenvironments.