title: Polysaccharide from Ganoderma atrum evokes antitumor activity via Toll-like receptor 4-mediated NF-κB and mitogen-activated protein kinase signaling pathways.
abstract: Ganoderma atrum has been used as a traditional Chinese medicine for centuries. In this study, the antitumor activity of a novel G. atrum polysaccharide (PSG-1) was investigated in vitro and in vivo using S180 tumor-bearing mice. The results showed that PSG-1 significantly inhibited the proliferation of S180 via the activation of macrophages in a dose-dependent manner. PSG-1-primed macrophages exhibited a higher tumoricidal activity than untreated macrophages. Administration of PSG-1 significantly inhibited the growth of transplantable sarcoma S180-bearing mice and increased macrophage phagocytosis and the levels of cytokines and nitride oxide. Expression of Toll-like receptor (TLR) 4 in the membrane was markedly increased in PSG-1-treated groups, suggesting that it may be a possible receptor for PSG-1. PSG-1 also promoted the translocation of the p65 subunit of NF-κB from cytosol to nucleus and the degradation of IκBα. Moreover, the phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2, and c-Jun N-terminal kinase in macrophages was improved by PSG-1 in a dose-dependent manner. Therefore, it is suggested that PSG-1 may elicit its antitumor effect by improving immune system functions through TLR4-mediated NF-κB and MAPK signaling pathways.
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China.
authors.forename: Shenshen
authors.initials: S
authors.lastname: Zhang
authors.forename: Shaoping
authors.initials: S
authors.lastname: Nie
authors.forename: Danfei
authors.initials: D
authors.lastname: Huang
authors.forename: Jianqin
authors.initials: J
authors.lastname: Huang
authors.forename: Yawei
authors.initials: Y
authors.lastname: Wang
authors.forename: Mingyong
authors.initials: M
authors.lastname: Xie
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D062610:Fungal Polysaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D032902:Ganoderma / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012509:Sarcoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D062610:Fungal Polysaccharides; C498145:Rela protein, rat; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA