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首页> 外文期刊>Molecular Cancer >6-Shogaol induces apoptosis in human leukemia cells through a process involving caspase-mediated cleavage of eIF2α
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6-Shogaol induces apoptosis in human leukemia cells through a process involving caspase-mediated cleavage of eIF2α

机译：6-Shogaol通过半胱天冬酶介导的eIF2α裂解过程诱导人白血病细胞凋亡

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Background 6-Shogaol is a promising antitumor agent isolated from dietary ginger ( Zingiber officinale ). However, little is known about the efficacy of 6-shogaol on leukemia cells. Here we investigated the underlying mechanism of 6-shogaol induced apoptosis in human leukemia cells in vitro and in vivo . Methods Three leukemia cell lines and primary leukemia cells were used to investigate the apoptosis effect of 6-shogaol. A shotgun approach based on label-free proteome with LC-CHIP Q-TOF MS/MS was employed to identify the cellular targets of 6-shogaol and the differentially expressed proteins were analyzed by bioinformatics protocols. Results The present study indicated that 6-shogaol selectively induced apoptosis in transformed and primary leukemia cells but not in normal cells. Eukaryotic translation initiation factor 2 alpha (eIF2α), a key regulator in apoptosis signaling pathway, was significantly affected in both Jurkat and U937 proteome profiles. The docking results suggested that 6-shogaol might bind well to eIF2α at Ser51 of the N-terminal domain. Immunoblotting data indicated that 6-shogaol induced apoptosis through a process involving dephosphorylation of eIF2α and caspase activation–dependent cleavage of eIF2α. Furthermore, 6-shogaol markedly inhibited tumor growth and induced apoptosis in U937 xenograft mouse model. Conclusion The potent anti-leukemia activity of 6-shogaol found both in vitro and in vivo in our study make this compound a potential anti-tumor agent for hematologic malignancies.
机译：背景6-Shogaol是一种从饮食生姜（姜）中分离出来的有前途的抗肿瘤药物。然而，关于6-松果酚对白血病细胞的功效知之甚少。在这里，我们研究了6-松果酚在体外和体内诱导人白血病细胞凋亡的潜在机制。方法以3种白血病细胞系和原代白血病细胞为材料，研究6-shogaol的凋亡作用。采用基于无标记蛋白质组和LC-CHIP Q-TOF MS / MS的shot弹枪方法鉴定6-shogaol的细胞靶标，并通过生物信息学方案分析差异表达的蛋白质。结果本研究表明6-松果酚选择性地诱导了转化的和原发性白血病细胞的凋亡，但不诱导正常细胞的凋亡。真核翻译起始因子2α（eIF2α），是细胞凋亡信号通路的关键调节因子，在Jurkat和U937蛋白质组谱中均受到显着影响。对接结果表明6-shogaol可能与N端结构域Ser51处的eIF2α结合良好。免疫印迹数据表明，6-松果酚通过涉及eIF2α的去磷酸化和胱天蛋白酶激活依赖性的eIF2α裂解的过程诱导凋亡。此外，在U937异种移植小鼠模型中，6-shogaol显着抑制肿瘤生长并诱导凋亡。结论我们研究中在体内和体外发现的6-shogaol具有很强的抗白血病活性，使该化合物成为血液系统恶性肿瘤的潜在抗肿瘤剂。

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