Fucoidan from Laminaria japonica exerts antitumor effects on angiogenesis and micrometastasis in triple-negative breast cancer cells

Int J Biol Macromol. 2020 Apr 15;149:600-608. doi: 10.1016/j.ijbiomac.2020.01.256. Epub 2020 Jan 28.


Fucoidan is a fucose-rich polysaccharide that has gained attention for its various anticancer properties. However, the effect and underlying mechanism of fucoidan on triple-negative breast cancer (TNBC) are still unknown. Herein, we investigated the anticancer potential of fucoidan from Laminaria japonica. We found that fucoidan showed modest antiproliferative activity against TNBC cells, while it effectively reduced migratory and invasive capacities. Mechanistically, fucoidan suppressed activation of MAPK and PI3K followed by inhibition of AP-1 and NF-κB signaling in TNBC. Additionally, fucoidan downregulated expressions of proangiogenic factors in TNBC cells, and fucoidan blocked tumor-elicited tube formation by human umbilical vascular endothelial cells (HUVECs). We also observed that fucoidan blocked tumor adhesion and invasion towards HUVECs. Surprisingly, fucoidan robustly suppressed tube formation on HUVECs. Moreover, fucoidan inhibited in vivo angiogenesis and micrometastasis in a transgenic zebrafish model. Together, L. japonica fucoidan exhibits potent antitumor effects by its attenuation of invasiveness and proangiogenesis in TNBC.

Keywords: Angiogenesis; Fucoidan; Invasion; Metastasis; Triple-negative breast cancer.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Laminaria / chemistry*
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • NF-kappa B / genetics
  • Neoplasm Micrometastasis
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Polysaccharides / chemistry
  • Polysaccharides / pharmacology*
  • Signal Transduction / drug effects
  • Transcription Factor AP-1 / genetics
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / pathology
  • Xenograft Model Antitumor Assays


  • NF-kappa B
  • Polysaccharides
  • Transcription Factor AP-1
  • fucoidan
  • Mitogen-Activated Protein Kinase Kinases