Induction of apoptosis by luteolin through cleavage of Bcl-2 family in human leukemia HL-60 cells
Induction of apoptosis by luteolin through cleavage of Bcl-2 family in human leukemia HL-60 cells
复制标题
DOI：
10.1016/j.ejphar.2004.12.026
复制
发表时间：
2005-02-10
影响因子：
5
通讯作者：
Pan, MH
中科院分区：
文献类型：
--
作者：
Cheng, AC;Huang, TC;Pan, MH
在我们的研究中，木犀草素在HL-60细胞中显示出诱导凋亡的作用，在100 muM处理下，木犀草素的凋亡率为76.5%。当HL-60细胞用60mum木犀草素处理时，DNA阶梯在6 h可见，并且在处理后6-12 h增加。木草素可以降低线粒体膜电位，触发细胞色素c释放到细胞质中，诱导procaspase-9和procaspase-3加工，并裂解多聚（adp -核糖）聚合酶（PARP）和DNA断裂因子（DFF-45）。在我们的研究中检测到促凋亡的Bcl-2蛋白，如Bad和Bax，被切割成其截短的形式，以及抗凋亡的Bcl-2蛋白，如Bcl-2和Bcl-X-L，被切割成其有效的促凋亡片段。由此提示木犀草素的结构与其诱导HL-60细胞凋亡的作用有关，线粒体途径可能在木犀草素诱导HL-60细胞凋亡中起重要作用。木犀草素诱导细胞凋亡可能是其肿瘤治疗和化学预防作用的关键机制。(C) 2004 Elsevier B.V.版权所有
In our study, luteolin has shown its apoptosis-inducing potent in HL-60 cells with its 76.5% apoptotic ratio of 100 muM treatment. When HL-60 cells were treated with 60 muM of luteolin, DNA ladders were visible at 6 h and increased from 6-12 h after treatment. Luteolin could decrease the mitochondrial membrane potential, trigger cytochrome c released to cytosol, and subsequently induce the processing of procaspase-9 and procaspase-3, which were followed by the cleavage of poly-(ADP-ribose) polymerase (PARP) and DNA fragmentation factor (DFF-45). The cleavage of the proapoptotic Bcl-2 proteins, such as Bad and Bax to produce their truncated forms, and the cleavage of the antiapoptotic Bcl-2 proteins, such as Bcl-2 and Bcl-X-L, into their potent pro-apoptotic fragments were detected in our study. From the results, we suggested that the structure of luteolin contributes to its potent in inducing apoptosis in HL-60 cells, and the mitochondrial pathway might play an important role in the luteolin-induced apoptosis. The induction of apoptosis by luteolin may offer a pivotal mechanism for its cancertherapeutic and chemopreventive action. (C) 2004 Elsevier B.V. All rights reserved.