Ganoderma lucidum induced apoptosis in NB4 human leukemia cells: Involvement of Akt and Erk
Ganoderma lucidum induced apoptosis in NB4 human leukemia cells: Involvement of Akt and Erk
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DOI：
10.1016/j.jep.2009.12.027
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发表时间：
2010-03-02
影响因子：
5.4
通讯作者：
Diez, Jose C.
中科院分区：
文献类型：
--
作者：
Calvino, Eva;Luis Manjon, Jose;Diez, Jose C.
本研究的最终目的是研究灵芝[Ganoderma Lucidul(Curtis)P.Karst.；Ganodermataceae Donk]组分对NB4人白血病细胞的毒性和诱导细胞凋亡的作用。材料和方法：从灵芝子实体中分离得到两个水提物和一个甲醇提取的柱层析半纯化组分。用流式细胞仪检测细胞存活率、细胞周期和DNA片段化，并定量检测细胞凋亡率。结果：水提物可轻微降低NB4细胞的存活率，并诱导细胞DNA片段化。甲醇提取的半纯化组分稀释到初始组分浓度的15%或40%时，通过诱导DNA片段化和诱导凋亡，显著降低了这些白血病细胞(处理19h)的存活率。此外，稀释到初始E3浓度的15%可导致p53水平降低，bcl2/bax关系降低，非磷酸化和磷酸化Akt(蛋白激酶Akt，蛋白激酶B)和Erk(ERK1和2)水平降低。结论：灵芝活性部位可诱导人白血病细胞发生凋亡和信号转导激酶(Akt和Erk)的变化。从灵芝化合物抗肿瘤作用的角度来看，这些数据可能具有重要的相关性。最终在白血病细胞中的治疗应用可能被开发出来。(C)2009爱思唯尔爱尔兰有限公司。保留所有权利。
Aim of the study: The final goal of this work was to study the toxic and apoptosis effects induced by fractions from Ganoderma lucidum [Ganoderma lucidum (Curtis) P. Karst.; Ganodermataceae Donk] on NB4 human leukemia cells.Materials and methods: Two aqueous extracts and a methanol-extracted column-chromatography semipurified fraction were obtained from Ganoderma lucidum fruiting body. Flow cytometry analyses were used to measure cell viability, cell cycle and DNA fragmentation and to quantify apoptosis. Western-blot analyses were used to quantify changes in apoptosis proteins and intracellular kinases.Results: Aqueous extracts slightly reduce cell viability and induce DNA fragmentation in NB4 cells. Methanol-extracted semipurified fraction at dilutions down to 15% or 40% of the initial fraction concentration reduced significantly the viability of these leukemia cells (treated for 19h) with induction of DNA fragmentation and induction of apoptosis. Overmore, the dilution down to 15% of the initial E3 concentration induced a reduction of p53 levels, of the Bcl2/Bax relationship as well as reduced levels of both unphosphorylated and phosphorylated Akt (Protein kinase Akt, protein kinase B) and Erk (Erk1 and 2).Conclusions: Induction of apoptosis and alterations in signal transduction kinases (Akt and Erk) are produced by active fractions from Ganoderma lucidum on human leukemia cells. These data could be of important relevance from the viewpoint of antitumor actions of compounds from Ganoderma lucidum. Eventual therapy applications in leukemia cells might be developed. (C) 2009 Elsevier Ireland Ltd. All rights reserved.