Antitumor and immunomodulatory activity of a water-soluble polysaccharide from Grifola frondosa

• Published in: Carbohydrate polymers 2015-12, Vol.134, p.406-412
• Main Authors: Mao, Guang-Hua, Ren, Yi, Feng, Wei-Wei, Li, Qian, Wu, Hui-Yu, jin, Dun, Zhao, Ting, Xu, Cai-Quan, Yang, Liu-Qing, Wu, Xiang-Yang
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Carbohydrate Sequence; Cell Line, Tumor; Cell Proliferation - drug effects; Cytokines - biosynthesis; Gene Expression Regulation, Neoplastic - drug effects; Grifola - chemistry; Grifola frondosa; Hep G2 Cells; Humans; Immunologic Factors - chemistry; Immunologic Factors - pharmacology; Macrophage Activation - drug effects; Macrophages - drug effects; Macrophages - immunology; Mice; Molecular Sequence Data; Nitric Oxide - secretion; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Phagocytosis - drug effects; Polysaccharide; Polysaccharides - chemistry; Polysaccharides - pharmacology; RAW 264.7 Cells; RAW264.7 cells; Solubility; Toll-like receptor (TLR); Tumor Necrosis Factor-alpha - genetics; Tumoricidal activity; Water - chemistry
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2015.08.020

•GP11 is composed of mannose, glucose and galactose in a molar ratio of 1:5.04:2.61.•GP11 significantly inhibits the growth of Heps tumor in vivo with no toxic.•GP11 exhibits its antitumor activity by improving immune system functions.•GP11 could up-regulate the expression of protein and gene via TLR-4 receptor. Grifola frondosa has long been known and respected as a medically important fungus. This study investigated the characterization, antitumor and immunomodulatory activity of a polysaccharide named GP11 purified from G. frondosa. The results revealed that GP11 was composed of →1)-d-Manp-(6→,→1)-d-Glcp-(4→,→1)-d-Galp-(6→and→2,3,6)-d-Glcp-(1→, with branches attached at O-2,3 of 1,2,3,6-linked Glcp residues and terminal T-Glcp. GP11 exhibited indirect cytotoxic activity against HepG-2 cells in vitro, and it significantly inhibited the growth of Heps cells in vivo. GP11 increased the relative thymus and spleen weights as well as serum tumor necrosis factor-alpha and interleukin-2 levels. GP11 stimulated tumoricidal activity and the production of nitric oxide (NO), TNF-α and interleukin-1β, and it also stimulated the protein expression of iNOS and mRNA expression of iNOS and TNF-α. TLR-4 is a potential receptor for GP11-mediated macrophage activation. The results suggested that the antitumor activity of GP11 may be due to the improvement of immune functions through the TLR-4-mediated up-regulation of NO and TNF-α.