Potential antitumor activity of a low-molecular-weight protein fraction from Grifola frondosa through enhancement of cytokine production.
Edible mushrooms contain an abundance of immune-enhancing nutritients. Some of these compounds, referred to as biological response modifiers (BRMs), have been used in biological therapies for cancer treatment. We obtained a low-molecular-weight protein fraction (MLP-Fraction) from the fruiting body of the maitake mushroom Grifola frondosa by multiple sequential steps, including ethanol precipitation, DEAE-exchange chromatography, and gel filtration. The effect of the MLP-Fraction on the immune system was determined using normal mice. This resulted in a simultaneous increase in splenocyte proliferation and production of cytokines such as interleukin (IL)-1alpha, tumor necrosis factor-alpha, IL-10, IL-12, and interferon (IFN)-gamma. The expression levels of IFN-gamma and IL-12 in antigen-presenting cells (APCs) and the activation of natural killer (NK) cells, macrophages, and dendritic cells were observed. These results suggest a mechanism in which NK cells are activated through cytokines produced by APCs. We also confirmed the possibility that the MLP-Fraction acts as a BRM using colon-26 carcinoma-bearing mice. This fraction enhanced the production of IL-12 and IFN-gamma by splenocytes in tumor-bearing mice and clearly showed an inhibitory effect on tumor cell growth.
Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Higashinada-ku, Kobe, Japan. kodaman@kobepharma-u.ac.jp
Noriko
N
Kodama
Shigeto
S
Mizuno
Hiroaki
H
Nanba
Naoaki
N
Saito
D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000276:immunology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D048690:Fruiting Bodies, Fungal; D005656:Fungal Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D048691:Grifola / Q000737:chemistry*; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012016:Reference Values; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D016207:Cytokines; D005656:Fungal Proteins; D007155:Immunologic Factors