Agaritine purified from Agaricus blazei Murrill exerts anti-tumor activity against leukemic cells
Agaritine purified from Agaricus blazei Murrill exerts anti-tumor activity against leukemic cells
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DOI：
10.1016/j.bbagen.2010.03.016
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发表时间：
2010-07-01
影响因子：
3
通讯作者：
Matsui, Taei
中科院分区：
文献类型：
--
作者：
Endo, Masahiro;Beppu, Hidehiko;Matsui, Taei
背景：蘑菇属蘑菇是一种常见的民间治疗癌症。活性成分，多糖和蛋白质-多糖复合物含有β-葡聚糖，已被分离，并显示出具有间接的肿瘤抑制活性，通过免疫activation.Methods：的热水提取物的Agaricus blazei Murrill（ABM）粉末的扩散级分，通过HPLC分级的基础上，在体外对白血病细胞的抗肿瘤活性。通过NMR和MS分析确定了抗肿瘤物质的结构。我们从ABM的扩散部分中纯化了一种杀肿瘤物质，并将其鉴定为蘑菇碱，β-N-（γ-L（+）-谷氨酰）-4-（羟甲基）苯肼，分子量为267 Da。该化合物抑制白血病细胞系如U937，MOLT 4，HL 60和K562的IC 50值分别为2.7、9.4、13.0和16.0 μ g/mL，但在浓度高达40 μ g/mL时对正常淋巴细胞无显著影响。虽然蘑菇碱已被怀疑具有遗传毒性或致癌性，蘑菇碱没有激活沙门氏菌的umu基因，这对致癌物质的反应。一般意义：结果表明，蘑菇碱从ABM有直接的抗肿瘤活性对白血病肿瘤细胞在体外。这与先前归因于该化合物的致癌活性相反。我们的研究结果还表明，这种活性与β-葡聚糖不同，后者间接抑制肿瘤细胞的增殖。(C)2010 Elsevier B. V.保留所有权利。
Background: Mushrooms of the genus Agaricus are a common folk remedy against carcinoma. The active ingredients, polysaccharides and protein-polysaccharide complexes containing beta-glucan, have been isolated and shown to have indirect tumor-suppressing activity via an immunological activation.Methods: The diffusible fraction of a hot-water extract of Agaricus blazei Murrill (ABM) powder was fractionated by HPLC based on the anti-tumor activity against leukemic cells in vitro. The structure of the anti-tumor substance was determined by NMR and MS analyses.Results: We purified a tumorcidal substance from the diffusible fraction of ABM and identified it as agaritine, beta-N-(gamma-L(+)-glutamyl)-4-(hydroxymethyl) phenylhydrazine, having a molecular mass of 267 Da. This compound inhibited the proliferation of leukemic cell lines such as U937, MOLT4, HL60 and K562 with IC50 values of 2.7, 9.4, 13.0, and 16.0 mu g/mL, respectively, but showed no significant effect on normal lymphatic cells at concentrations up to 40 mu g/mL. Although agaritine has been suspected of having genotoxic or carcinogenic properties, agaritine did not activate the umu gene of Salmonella, which reacts to carcinogens.General significance: The results indicate that agaritine from ABM has direct anti-tumor activity against leukemic tumor cells in vitro. This is in contrast to the carcinogenic activity previously ascribed to this compound. Our results also show that this activity is distinct from that of beta-glucan, which indirectly suppresses proliferation of tumor cells. (C) 2010 Elsevier B.V. All rights reserved.