Oral administration of an Enoki mushroom protein FVE activates innate and adaptive immunity and induces anti-tumor activity against murine hepatocellular carcinoma.
FVE is a documented immunomodulatory protein purified from Enoki mushroom (Flammulina velutipes) and known as an activator for human T lymphocytes. This present study was aimed to investigate the anti-tumor effect and the related mechanisms of oral administration of FVE using a murine hepatoma model. Oral administration of FVE (10mg/kg) significantly increased the life span and inhibited the tumor size of BNL 1MEA.7R.1 (BNL) hepatoma-bearing mice. Tumor-bearing mice receiving oral FVE treatment had the highest tumoricidal capacity of peritoneal macrophages and tumor-specific splenocytes against BNL hepatoma cells. In addition, in vivo neutralization of interferon-gamma (IFN-gamma) demonstrated a significant decrease of FVE-induced anti-tumor effect (P<0.05). The expression levels of major histocompatibility complex (MHC) class I and II molecules and costimulatory molecule CD80 on peripheral blood mononuclear cells obtained from the FVE-treated mice were upregulated as compared with those of the PBS-treated mice. Furthermore, immunohistochemical staining showed a strong inhibition of tumor growth and angiogenesis in hepatoma tissues after oral administration of FVE. Taken together, oral administration of FVE displayed anti-tumor activity through activating both innate and adaptive immunity of the host to prime a cytotoxic immune response and IFN-gamma played a key role in the anti-tumor efficacy of FVE.
Chang
Hui-Hsin
HH
Department of Horticulture, National Taiwan University, Taipei, Taiwan, ROC.
Hsieh
Kuang-Yang
KY
Yeh
Chen-Hao
CH
Tu
Yuan-Ping
YP
Sheu
Fuu
F
D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D005260:Female; D055393:Flammulina / Q000276:immunology*; D005656:Fungal Proteins / Q000008:administration & dosage*; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D007113:Immunity, Innate / Q000187:drug effects; D007155:Immunologic Factors / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008113:Liver Neoplasms / Q000188:drug therapy*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D018122:B7-1 Antigen; C547132:FIP-fve protein, Flammulina velutipes; D005656:Fungal Proteins; D007155:Immunologic Factors; D007371:Interferon-gamma