Fucans, but not fucomannoglucuronans, determine the biological activities of sulfated polysaccharides from Laminaria saccharina brown seaweed

PLoS One. 2011 Feb 28;6(2):e17283. doi: 10.1371/journal.pone.0017283.


Sulfated polysaccharides from Laminaria saccharina (new name: Saccharina latissima) brown seaweed show promising activity for the treatment of inflammation, thrombosis, and cancer; yet the molecular mechanisms underlying these properties remain poorly understood. The aim of this work was to characterize, using in vitro and in vivo strategies, the anti-inflammatory, anti-coagulant, anti-angiogenic, and anti-tumor activities of two main sulfated polysaccharide fractions obtained from L. saccharina: a) L.s.-1.0 fraction mainly consisting of O-sulfated mannoglucuronofucans and b) L.s.-1.25 fraction mainly composed of sulfated fucans. Both fractions inhibited leukocyte recruitment in a model of inflammation in rats, although L.s.-1.25 appeared to be more active than L.s.-1.0. Also, these fractions inhibited neutrophil adhesion to platelets under flow. Only fraction L.s.-1.25, but not L.s.-1.0, displayed anticoagulant activity as measured by the activated partial thromboplastin time. Investigation of these fractions in angiogenesis settings revealed that only L.s.-1.25 strongly inhibited fetal bovine serum (FBS) induced in vitro tubulogenesis. This effect correlated with a reduction in plasminogen activator inhibitor-1 (PAI-1) levels in L.s.-1.25-treated endothelial cells. Furthermore, only parent sulfated polysaccharides from L. saccharina (L.s.-P) and its fraction L.s.-1.25 were powerful inhibitors of basic fibroblast growth factor (bFGF) induced pathways. Consistently, the L.s.-1.25 fraction as well as L.s.-P successfully interfered with fibroblast binding to human bFGF. The incorporation of L.s.-P or L.s.-1.25, but not L.s.-1.0 into Matrigel plugs containing melanoma cells induced a significant reduction in hemoglobin content as well in the frequency of tumor-associated blood vessels. Moreover, i.p. administrations of L.s.-1.25, as well as L.s.-P, but not L.s.-1.0, resulted in a significant reduction of tumor growth when inoculated into syngeneic mice. Finally, L.s.-1.25 markedly inhibited breast cancer cell adhesion to human platelet-coated surfaces. Thus, sulfated fucans are mainly responsible for the anti-inflammatory, anticoagulant, antiangiogenic, and antitumor activities of sulfated polysaccharides from L. saccharina brown seaweed.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / metabolism
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology
  • Anticoagulants / metabolism
  • Anticoagulants / pharmacology
  • Biological Products / chemistry
  • Biological Products / metabolism
  • Biological Products / pharmacology*
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology
  • Female
  • Fucose / chemistry
  • Fucose / physiology
  • Humans
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Laminaria / chemistry*
  • Laminaria / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / drug effects
  • Phaeophyta / chemistry
  • Phaeophyta / metabolism
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism
  • Polysaccharides / pharmacology
  • Polysaccharides / physiology*
  • Rats
  • Rats, Wistar
  • Seaweed / chemistry
  • Seaweed / metabolism


  • Angiogenesis Inhibitors
  • Anti-Inflammatory Agents
  • Anticoagulants
  • Biological Products
  • Polysaccharides
  • Fucose
  • fucoidan