EPS364, a Novel Deep-Sea Bacterial Exopolysaccharide, Inhibits Liver Cancer Cell Growth and Adhesion

Mar Drugs. 2021 Mar 22;19(3):171. doi: 10.3390/md19030171.

Abstract

The prognosis of liver cancer was inferior among tumors. New medicine treatments are urgently needed. In this study, a novel exopolysaccharide EPS364 was purified from Vibrio alginolyticus 364, which was isolated from a deep-sea cold seep of the South China Sea. Further research showed that EPS364 consisted of mannose, glucosamine, gluconic acid, galactosamine and arabinose with a molar ratio of 5:9:3.4:0.5:0.8. The relative molecular weight of EPS364 was 14.8 kDa. Our results further revealed that EPS364 was a β-linked and phosphorylated polysaccharide. Notably, EPS364 exhibited a significant antitumor activity, with inducing apoptosis, dissipation of the mitochondrial membrane potential (MMP) and generation of reactive oxygen species (ROS) in Huh7.5 liver cancer cells. Proteomic and quantitative real-time PCR analyses indicated that EPS364 inhibited cancer cell growth and adhesion via targeting the FGF19-FGFR4 signaling pathway. These findings suggest that EPS364 is a promising antitumor agent for pharmacotherapy.

Keywords: FGF19-FGFR4 signaling; antitumor; cell adhesion; cell growth; exopolysaccharide.

MeSH terms

  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Adhesion / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Fibroblast Growth Factors / metabolism
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Molecular Structure
  • Polysaccharides, Bacterial / isolation & purification
  • Polysaccharides, Bacterial / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Receptor, Fibroblast Growth Factor, Type 4 / metabolism
  • Signal Transduction
  • Structure-Activity Relationship
  • Vibrio alginolyticus / metabolism*

Substances

  • Antineoplastic Agents
  • FGF19 protein, human
  • Polysaccharides, Bacterial
  • Reactive Oxygen Species
  • Fibroblast Growth Factors
  • FGFR4 protein, human
  • Receptor, Fibroblast Growth Factor, Type 4