Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis
Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis
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DOI：
10.1007/s002620050473
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发表时间：
1998-05-01
影响因子：
5.8
通讯作者：
Katakura, R
中科院分区：
文献类型：
--
作者：
Fujimiya, Y;Suzuki, Y;Katakura, R
我们已经从担子菌菌株--巴西蘑菇中分离出一种新型的天然杀肿瘤产物。在Balb/c小鼠中使用双移植肿瘤系统，用从子实体获得的酸处理级分（ATF）治疗原发性肿瘤导致具有显著杀肿瘤活性的自然杀伤（NK）细胞浸润远处肿瘤。如电泳和DNA片段化分析所示，ATF还通过诱导凋亡过程直接抑制体外肿瘤细胞生长;如流式细胞术分析所示，这种凋亡作用还通过肿瘤细胞线粒体膜上Apo2.7抗原表达增加来证明。ATF对正常小鼠脾脏或白细胞介素2处理的脾脏单核细胞没有影响，表明它对肿瘤细胞具有选择性细胞毒性。细胞周期分析表明，ATF诱导MethA肿瘤细胞S期丢失，但不影响正常脾单个核细胞，主要是在G 0 G1期。各种色谱聚焦纯化步骤和NMR分析表明，杀肿瘤活性主要存在于含有（1->4）-α-D-葡聚糖和（1->6）-β-D-葡聚糖的级分中，在ATF（分子量170 kDa）中以约1：2的比例存在，而最终纯化的级分HM 3-G（分子量380 kDa）具有最高的杀肿瘤活性，由超过90%的葡萄糖组成，主要组分是具有（1->6）-β分支的（1->4）-α-D-葡聚糖，比例约为4：1。
We have isolated a novel type of natural tumoricidal product from the basidiomycete strain, Agaricus blazei Murill. Using the double-grafted tumor system in Balb/c mice, treatment of the primary tumor with an acid-treated fraction (ATF) obtained from the fruit bodies resulted in infiltration of the distant tumor by natural killer (NK) cells with marked tumoricidal activity. As shown by electrophoresis and DNA fragmentation assay, the ATF also directly inhibited tumor cell growth in vitro by inducing apoptotic processing; this apoptotic effect was also demonstrated by increased expression of the Apo2.7 antigen on the mitochondrial membranes of tumor cells, as shown by flow-cytometric analysis. The ATF had no effect on normal mouse splenic or interleukin-2-treated splenic mononuclear cells, indicating that it is selectively cytotoxic for the tumor cells. Cell-cycle analysis demonstrated that ATF induced the loss of S phase in MethA tumor cells, but did not affect normal splenic mononuclear cells, which were mainly in the G0G1 phase. Various chromatofocussing purification steps and NMR analysis showed the tumoricidal activity to be chiefly present in fractions containing (1-->4)-alpha-D-glucan and (1-->6)-beta-D-glucan, present in a ratio of approximately 1:2 in the ATF (molecular mass 170 kDa), while the final purified fraction, HM3-G (molecular mass 380 kDa), with the highest tumoricidal activity, consisted of more than 90% glucose, the main component being (1-->4)-alpha-D-glucan with (1-->6)-beta branching, in the ratio of approximately 4:1.