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

Int J Biol Macromol. 2017 Jan;94(Pt A):451-458. doi: 10.1016/j.ijbiomac.2016.10.046. Epub 2016 Oct 17.

Abstract

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 57kD, 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.

Keywords: Angiogenesis; Hypoxia-inducible factor-1 alpha; Matrix metalloproteinase-2; Polysaccharide; Sargassum thunbergii; Vascular endothelial growth factor-A.

MeSH terms

  • A549 Cells
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / isolation & purification
  • Angiogenesis Inhibitors / pharmacology*
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Down-Regulation
  • Drug Screening Assays, Antitumor
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Matrix Metalloproteinase 2 / metabolism*
  • Polysaccharides / chemistry
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology*
  • Sargassum / chemistry
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / physiology

Substances

  • Angiogenesis Inhibitors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Polysaccharides
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MMP2 protein, human
  • Matrix Metalloproteinase 2