A polysaccharide from Sargassum thunbergii inhibits angiogenesis via downregulating MMP-2 activity and VEGF/HIF-1α signaling

A water-soluble polysaccharide (STPC2) was isolated from the boiling-water extract of Sargassum thunbergii, purified by CaCl2 precipitation and chromatography on DEAE-cellulose and Sephacryl S-300 column. It was found that STPC2, with a molecular weight of 57 kD, was composed of fucose, xylose, galactose and glucuronic acid, in a ratio of 8.1: 3.8: 2.1: 1.0. Additionally, we found that STPC2 significantly inhibited endothelial cell migration and tube formation without toxicity. Moreover, STPC2 significantly inhibited lung cancer cell A549 migration and proliferation. It was found that STPC2 treatment suppressed MMP-2 gene expression at transcriptional level and enzymatic activity. Furthermore, STPC2 reduced the mRNA and protein expression of vascular endothelial growth factor-A (VEGF-A) and hypoxia-inducible factor (HIF)-1 alpha in the endothelial cells. Taken together, our findings indicated that STPC2 was a potent bioactive polysaccharide with distinct anti-angiogenesis activity against tumor migration via down-regulation of MMP-2 activity and VEGF/HIF-1α signaling pathway.