Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells
Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells
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DOI：
10.1002/mc.20031
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发表时间：
2004-08-01
影响因子：
4.6
通讯作者：
Srinivas, G
中科院分区：
文献类型：
--
作者：
Srinivas, P;Gopinath, G;Srinivas, G
有新的证据表明白花丹素（5-羟基-2-甲基-1, 4-萘醌）可能具有作为化疗药物的潜力。然而，白花丹素的生长抑制机制尚未被探索。该研究的目的是确定白花丹素诱导的人宫颈癌细胞系 ME-180 中的细胞死亡是否表现出细胞凋亡的生化特征，并检查自由基清除剂 N-乙酰基-L-半胱氨酸 (NAC) 是否可以逆转白花丹素的细胞毒性作用。从结果可以看出，白花丹素以浓度和时间依赖性方式抑制ME-180细胞的生长。如目前数据所证明的，白花丹素诱导细胞死亡的细胞毒性作用是通过活性氧（ROS）的产生和随后诱导细胞凋亡来实现的。用白花丹素处理细胞会导致线粒体膜电位 (DeltaPsi(m)) 损失和细胞凋亡特征的形态变化，例如磷脂酰丝氨酸易位、核浓缩和 DNA 片段化。此外，白花丹素诱导的细胞凋亡涉及线粒体细胞色素 c 和凋亡诱导因子 (AIF) 的释放，从而激活 caspase 依赖性和非依赖性途径，如白花丹素介导的 caspase-3 和 -9 激活所示。我们的结果还表明，用 NAC 预处理 ME-180 细胞可阻止白花丹素诱导的 DeltaPsi(m) 损失以及随后细胞色素 c、AIF 的释放以及 caspase-9 和 -3 的激活，从而抑制白花丹素的凋亡能力。 (C) 2004 Wiley-Liss, Inc.
There is an emerging evidence that plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone) may have potential as a chemotherapeutic agent. However, the growth inhibitory mechanisms of plumbagin have remained unexplored. The aim of the study was to determine whether plumbagin-induced cell death in human cervical cancer cell line, ME-180, exhibited biochemical characteristics of apoptosis and to check whether N-acetyl-L-cysteine (NAC), which is a free radical scavenger, can reverse the cytotoxic effects of plumbagin. It can be concluded from the results that plumbagin inhibits the growth of ME-180 cells in a concentration and time-dependent manner. The cytotoxic effect of plumbagin induced cell death is through the generation of reactive oxygen species (ROS) and subsequent induction of apoptosis as demonstrated by the present data. Treatment of cells with plumbagin caused loss of mitochondrial membrane potential (DeltaPsi(m)), and morphological changes characteristic of apoptosis, such as the translocation of phosphatidyl serine, nuclear condensation, and DNA fragmentation. Moreover, plumbagin-induced apoptosis involved release of mitochondrial cytochrome c and apoptosis inducing factor (AIF), thus activation of caspase-dependent and -independent pathways, as shown by the plumbagin-mediated activation of caspase-3 and -9. Our results also show that pretreatment of ME-180 cells with NAC blocks plumbagin-induced loss of DeltaPsi(m) and subsequent release of cytochrome c, AIF, and caspase-9 and -3 activation, thus inhibiting the apoptotic ability of plumbagin. (C) 2004 Wiley-Liss, Inc.