Potential Antitumor Activity of a Low-Molecular-Weight Protein Fraction from Grifola frondosa Through Enhancement of Cytokine Production
Potential Antitumor Activity of a Low-Molecular-Weight Protein Fraction from Grifola frondosa Through Enhancement of Cytokine Production
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DOI：
10.1089/jmf.2009.1029
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发表时间：
2010-02-01
影响因子：
2.4
通讯作者：
Saito, Naoaki
中科院分区：
文献类型：
--
作者：
Kodama, Noriko;Mizuno, Shigeto;Saito, Naoaki
食用菌含有丰富的增强免疫力的营养素。其中一些化合物被称为生物反应调节剂(BRM)，已被用于癌症治疗的生物疗法。采用乙醇沉淀、DEAE交换层析、凝胶过滤等步骤，从灰树菇子实体中分离得到一种低分子量蛋白质组分。用正常小鼠测定MLP组分对免疫系统的影响。这导致脾细胞增殖和细胞因子的产生同时增加，如白介素1α、肿瘤坏死因子α、白介素10、白介素12和干扰素γ。观察抗原提呈细胞(APC)中干扰素-γ和IL-12的表达水平及自然杀伤细胞(NK)、巨噬细胞和树突状细胞的活化情况。这些结果提示了NK细胞通过APC产生的细胞因子被激活的机制。我们还证实了MLP组分在结肠癌-26荷瘤小鼠身上发挥BRM作用的可能性。该组分可促进荷瘤小鼠脾细胞产生IL-12和干扰素-γ，并明显抑制肿瘤细胞生长。
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)-1 alpha, 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.