Effect of chitosan oligosaccharide-conjugated selenium on improving immune function and blocking gastric cancer growth

Eur J Pharmacol. 2021 Jan 15:891:173673. doi: 10.1016/j.ejphar.2020.173673. Epub 2020 Oct 22.

Abstract

Selenium (Se) is a potential chemopreventive or chemotherapeutic agent against malignant tumor. Selenium-oligosaccharides are important selenium source of dietary supplementation. Due to the insufficient natural production, it is therefore urgent to develop selenium-oligosaccharides by artificial synthesis. Chitosan, the N-deacetylated derivative of chitin, has been applied widely in biomedical field, owing to its nontoxicity, hydrophilicity, biocompatibility, and biodegradation. While chitosan is water insoluble at neutral pH, limiting its application in physiological conditions. Chitosan oligosaccharide (COS), the hydrolysate of chitosan, is readily soluble in water because of the shorter chain lengths of the oligomers and the free amino groups in the D-glucosamine units. This study was aimed at preparing COS-conjugated selenium (COS-Se) and examining the toxicity and ability on improving immune function and blocking gastric cancer growth. Our results demonstrated that COS-Se displayed directly co-mitogenic and mitogenic actions on mouse splenocytes proliferation in vitro. Besides, COS-Se treatment could effectively elevate phagocytosis and increase the secretion of anti-inflammatory cytokine in mouse peritoneal macrophages. Further in vivo experiments showed that COS-Se exhibited immuno-enhancing effects through promoting the phagocytic index, spleen index and thymus index with no obvious toxicity to Kunming mice. Moreover, COS-Se inhibited proliferation and metastasis of human gastric cancer cells, with non-toxic effects on the normal fibroblast cells in vitro. COS-Se supplementation could significantly repress the growth of gastric adenocarcinoma through reducing levels of CD34, vascular endothelial growth factor and matrix metalloproteinase-9 of nude mice. In conclusion, COS-Se was non-toxic and showed great potential as a functional food ingredient in cancer prevention.

Keywords: Chitosan oligosaccharide; Gastric cancer; Immune function; Selenium.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chitosan / chemistry*
  • Cytokines / metabolism
  • Drug Compounding
  • Female
  • Humans
  • Immune System / drug effects*
  • Immune System / immunology
  • Immune System / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Oligosaccharides / chemistry*
  • Phagocytosis / drug effects
  • Selenium / chemistry
  • Selenium / pharmacology*
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Cytokines
  • Oligosaccharides
  • Chitosan
  • Selenium