Potential Antitumor Activity of a Low-Molecular-Weight Protein Fraction from Grifola frondosa Through Enhancement of Cytokine Production
Noriko Kodama,1,2 Shigeto Mizuno,3 Hiroaki Nanba,4 and Naoaki Saito1
1Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University; and Departments of 2Basic Educational Center for Pharmacy and 3Medical Pharmaceutics, 4Kobe Pharmaceutical University, Kobe, Japan
ABSTRACT 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)-1a, tumor necrosis factor-a, IL-10, IL-12, and interferon (IFN)-y. The expression levels of IFN-y 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-y by splenocytes in tumor-bearing mice and clearly showed an inhibitory effect on tumor cell growth.