Induction of caspase-3-dependent apoptosis in human leukemia HL-60 cells by paclitaxel
Induction of caspase-3-dependent apoptosis in human leukemia HL-60 cells by paclitaxel
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DOI：
10.1016/j.cccn.2005.02.003
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发表时间：
2005-07-01
影响因子：
5
通讯作者：
Chung, JG
中科院分区：
文献类型：
--
作者：
Lu, KH;Lue, KH;Chung, JG
背景：紫杉醇是一种抗肿瘤药物，可抑制人白血病HL-60细胞的生长和细胞周期进程，诱导细胞凋亡。Caspase-3在细胞蛋白的蛋白水解裂解过程中起直接作用，从而导致细胞凋亡。方法：采用流式细胞术和Western blotting检测紫杉醇作用后HL-60细胞的细胞形态和凋亡情况，并检测加或不加z-VAD-fmk（广谱caspase抑制剂）预处理的caspase-3活性。结果：(1)紫杉醇主要诱导HL-60细胞G2/M细胞周期阻滞（p < 0.001）；(2)紫杉醇诱导HL-60细胞凋亡呈时间依赖性（p < 0.001）和剂量依赖性（p < 0.001）；(3)在HL-60细胞中，z-VAD-fmk抑制紫杉醇诱导的凋亡（12 h: p < 0.001; 24 h: p < 0.01; 48 h: p < 0.01; 72 h: p < 0.001）和caspase-3激活（12 h: p < 0.05; 24 h: p < 0.01; 48 h: p < 0.01; 72 h: p < 0.01）。结论：紫杉醇可通过caspase-3活性诱导HL-60细胞G2/M周期转变和凋亡。(c) 2005 Elsevier B.V.版权所有
Background: Paclitaxel, an antineoplastic drug, inhibits cell growth and cell cycle progression and induces apoptosis in human leukemia HL-60 cells. Caspase-3 plays a direct role in proteolytic cleavage of cellular proteins responsible for progression to apoptosis.Methods: We examined the cell morphology and apoptosis in HL-60 cells after exposure to paclitaxel and measured caspase-3 activities with or without z-VAD-fmk (a broad-spectrum caspase inhibitor) pretreatment by flow cytometric analysis and Western blotting.Results: Together, our results were (1) paclitaxel mainly induced G2/M cell cycle arrest in HL-60 cells (p < 0.001); (2) time (p < 0.001)- and dose-dependent (p < 0.001) apoptosis of HL-60 cells was induced by paclitaxel; (3) in HL-60 cells, z-VAD-fmk blocked paclitaxel-induced apoptosis (12 h: p < 0.001; 24 h: p < 0.01; 48 h: p < 0.01; 72 h: p < 0.001) and caspase-3 activation (12 h: p < 0.05; 24 h: p < 0.01; 48 h: p < 0.01; 72 h: p < 0.01).Conclusions: These results suggest that paclitaxel can induce G2/M cell cycle transition and apoptosis via caspase-3 activity in HL-60 cells. (c) 2005 Elsevier B.V. All rights reserved.