title: Structure of a β-glucan from Grifola frondosa and its antitumor effect by activating Dectin-1/Syk/NF-κB signaling.
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.
authors: Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors: Jianping
authors: J
authors: Fang
authors: Ying
authors: Y
authors: Wang
authors: Xiaofen
authors: X
authors: Lv
authors: Xiaokun
authors: X
authors: Shen
authors: Xinyan
authors: X
authors: Ni
authors: Kan
authors: K
authors: Ding
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D048690:Fruiting Bodies, Fungal / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005936:Glucans; D048691:Grifola / Q000737:chemistry*; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000819:agonists* / Q000235:genetics; D037181:Lectins, C-Type / Q000819:agonists / Q000737:chemistry* / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000819:agonists* / Q000235:genetics; D010587:Phagocytosis / Q000187:drug effects; D011134:Polysaccharides / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012509:Sarcoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D047071:beta-Glucans / Q000494:pharmacology* / Q000627:therapeutic use; D000099181:Dectin-1
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005936:Glucans; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D016328:NF-kappa B; D011134:Polysaccharides; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; D000099181:Dectin-1; C008247:laminaran; C000606897:Syk protein, mouse