Fucoidan MF4 from Fucus vesiculosus inhibits Lewis lung cancer via STING-TBK1-IRF3 pathway

Int J Biol Macromol. 2024 May;267(Pt 1):131336. doi: 10.1016/j.ijbiomac.2024.131336. Epub 2024 Apr 5.

Abstract

Fucoidan, a sulfated polysaccharide of marine origin found in brown algae and sea cucumbers, has been identified as a neuroprotective compound. In this study, a novel fucoidan MF4 was extracted from Fucus vesiculosus and isolated using Q-Sepharose fast-flow ion-exchange chromatography. The physicochemical properties of MF4 were characterized. MF4 is primarily composed of fucose, xylose, galactose, glucose, and mannose in a molar ratio of 12.3: 4.9: 1.1: 1.0: 1.1, with an average molecular weight of 67.7 kDa. Notably, MF4 demonstrated suppression of LLC tumor growth in vivo. RNA-sequencing analysis revealed that MF4 enhanced the expression of type I interferon-associated downstream genes in macrophages. Furthermore, MF4 increased the levels of phosphorylated TBK1 and IRF3 proteins in vitro. By activating the STING-TBK1-IRF3 signaling pathway, MF4 may enhance the antitumor activity of macrophages. Taken together, MF4 has promising potential as an antitumor and immunomodulatory agent.

Keywords: Antitumor; Fucoidan; STING.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Lewis Lung* / drug therapy
  • Carcinoma, Lewis Lung* / metabolism
  • Carcinoma, Lewis Lung* / pathology
  • Cell Line, Tumor
  • Interferon Regulatory Factor-3* / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Polysaccharides* / chemistry
  • Polysaccharides* / isolation & purification
  • Polysaccharides* / pharmacology
  • Protein Serine-Threonine Kinases* / metabolism
  • RAW 264.7 Cells
  • Signal Transduction* / drug effects

Substances

  • Polysaccharides
  • fucoidan
  • Interferon Regulatory Factor-3
  • Protein Serine-Threonine Kinases
  • Tbk1 protein, mouse
  • Membrane Proteins
  • Antineoplastic Agents
  • Irf3 protein, mouse