Antiangiogenic effects of GFP08, an agaran-type polysaccharide isolated from Grateloupia filicina.

An agaran-type polysaccharide, GFP08, isolated from Grateloupia filicina (C. Agardh) Lamouroux, was mainly composed of 1,3-linked β-D-galactose partially sulfated at position O-2 and 1,4-linked α-L-galactose O-2, O-3-disulfate, α-L-galactose O-6-sulfate and 3,6-anhydro-α-L-galactose. Small quantities of xylose, 4,6-O-(1'-carboxyethylidene) and 6-O-methyl-β-D-galactose were also present. In mice bearing sarcoma-180 cells, GFP08 decreased tumor weight in a dose-dependent manner. The antiangiogenic activity of GFP08 was evaluated using the chicken chorioallantoic membrane assay, and the results showed that GFP08 dose-dependently reduced new vessel formation. Meanwhile, GFP08 inhibited the differentiation of human umbilical vein endothelial cells (HUVECs) into capillary-like structures in vitro and reduced the number of migrated cells. However, there was no observed cytotoxicity of GFP08 toward HUVECs. Further study revealed that GFP08 decreased tissue factor (TF) expression without affecting the activities of matrix metalloproteinase-2 and -9. All those data indicated that GFP08 had an antitumor effect that might be associated in part with its antiangiogenic effect through down-regulating the expression of TF protein.