Structure of a β-glucan From Grifola Frondosa and Its Antitumor Effect by Activating Dectin-1/Syk/NF-κB Signaling

Glycoconj J. 2012 Aug;29(5-6):365-77. doi: 10.1007/s10719-012-9416-z. Epub 2012 Jun 29.

Abstract

A soluble homogeneous β-glucan, GFPBW1, with a molecular mass of 300 kDa was purified from the fraction of the fruit bodies of Grifola frondosa extracted with 5% NaOH. Using various methods, such as infrared spectroscopy, NMR, methylation and monosaccharide composition analysis, its structure was determined to be a β-D-(1-3)-linked glucan backbone with a single β-D-(1-6)-linked glucopyranosyl residue branched at C-6 on every third residue. It induced TNF-α and IL-6 production and the activation of Syk and NF-κB signaling in resident peritoneal macrophages from ICR mice, which could be significantly inhibited by the blocking reagent laminarin. A competitive phagocytosis assay with FITC-zymosan indicated that GFPBW1 could bind to DC-associated C-type lectin 1 (Dectin-1). The TNF-α secretion and activation of Syk/NF-κB signaling triggered by GFPBW1 were enhanced in RAW264.7 cells overexpressing wild but not mutant (Δ38 and Y15S) Dectin-1. Furthermore, GFPBW1 potentiated the Concanavalin A-induced proliferative response of splenocytes and inhibited Sarcoma-180 growth allografted in ICR mice but not in immunodeficient BALB/c nu/nu mice. These results suggested that the antitumor activity of GFPBW1 was partially associated with the activation of macrophages via the Dectin-1/Syk/NF-κB signaling pathway. This molecule could be a promising biological response modifier with clear application for antitumor therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Carbohydrate Sequence
  • Cell Line, Tumor
  • Fruiting Bodies, Fungal / chemistry
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glucans
  • Grifola / chemistry*
  • Injections, Subcutaneous
  • Interleukin-6 / biosynthesis
  • Intracellular Signaling Peptides and Proteins / agonists*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Lectins, C-Type / agonists
  • Lectins, C-Type / chemistry*
  • Lectins, C-Type / genetics
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / drug effects
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / agonists*
  • NF-kappa B / genetics
  • Phagocytosis / drug effects
  • Polysaccharides / pharmacology
  • Protein-Tyrosine Kinases / genetics
  • Sarcoma / drug therapy*
  • Sarcoma / genetics
  • Sarcoma / metabolism
  • Sarcoma / pathology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Syk Kinase
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Xenograft Model Antitumor Assays
  • beta-Glucans / pharmacology*
  • beta-Glucans / therapeutic use

Substances

  • Antineoplastic Agents, Phytogenic
  • Glucans
  • Interleukin-6
  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • NF-kappa B
  • Polysaccharides
  • Tumor Necrosis Factor-alpha
  • beta-Glucans
  • dectin 1
  • laminaran
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse