Effects of lycorine on HL-60 cells via arresting cell cycle and inducing apoptosis
Effects of lycorine on HL-60 cells via arresting cell cycle and inducing apoptosis
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DOI：
10.1016/j.febslet.2004.10.095
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发表时间：
2004-12-17
期刊：
影响因子：
3.5
通讯作者：
Li, Y
中科院分区：
文献类型：
--
作者：
Liu, J;Hu, WX;Li, Y
石蒜碱是从石蒜科植物中提取的一种天然抗癌生物碱，对肿瘤细胞具有多种生物学效应。石蒜碱作用于HL-60细胞后，细胞存活率呈剂量依赖性下降，半数抑制浓度（IC_（50））为1 μ M，细胞周期阻滞于G_2/M期，细胞生长减慢，细胞再生能力受到抑制。HL-60细胞呈现典型的凋亡形态学改变，凋亡DNA呈“梯状”，细胞时相分布出现亚G1峰，显示HL-60细胞凋亡。为进一步了解石蒜碱诱导HL-60细胞凋亡的分子机制，采用比色法检测caspase活性，Western blotting检测Bcl-2和Bax蛋白表达。caspase-8、caspase-9、caspase-3活性的增加表明caspase是石蒜碱诱导的细胞凋亡途径中的一个关键介质。Bcl-2蛋白低表达和Bax/Bcl-2比值升高表明Bcl-2家族蛋白参与了细胞凋亡。结果表明石蒜碱可通过阻滞细胞周期和诱导肿瘤细胞凋亡来抑制白血病细胞的生长，降低细胞存活率。(C)2004年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
As a natural anti-cancer alkaloid extracted from Amaryllidaceae, lycorine shows various biological effects on tumor cells. The survival rate of HL-60 cells exposed to lycorine was decreased in a dose-dependent manner with 1 muM as the 50% inhibitory concentration (IC50), cell growth was slowed down by arresting cell cycle at G2/M phase, and cell regeneration potential was inhibited. HL-60 cells exhibited typical apoptotic morphological changes, apoptotic DNA "ladder" pattern, and sub-G1 peak in cell phase distribution, showing apoptosis of HL-60 cells. To further understand the apoptotic molecular mechanism of lycorine on HL-60 cells, caspase activity was tested by colorimetric assay, and the expression of Bcl-2 and Bax proteins was examined by Western blotting. The increase of caspase-8, -9, -3 activities demonstrated that caspase was a key mediator of apoptotic pathways induced by lycorine. Under-expression of Bcl-2 and increase of Bax:Bcl-2 ratio showed that Bcl-2 family proteins were involved in apoptosis. Our finding suggests that lycorine can suppress leukemia growth and reduce cell survival via arresting cell cycle and inducing apoptosis of tumor cells. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.