Inhibition of cell proliferation and migration by oxidative stress from ascorbate-driven juglone redox cycling in human bladder-derived T24 cells
Inhibition of cell proliferation and migration by oxidative stress from ascorbate-driven juglone redox cycling in human bladder-derived T24 cells
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DOI：
10.1016/j.bbrc.2012.03.150
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发表时间：
2012-05-04
影响因子：
3.1
通讯作者：
Buc Calderon, P.
中科院分区：
文献类型：
--
作者：
Kviecinski, M. R.;Pedrosa, R. C.;Buc Calderon, P.
胡桃醌对T24细胞的影响进行了评估，在存在和不存在的抗坏血酸。在抗坏血酸存在下，胡桃醌在24小时的EC 50值从28.5 μ M降低到6.3 μ M。在胡桃醌处理的细胞中，抗坏血酸增加ROS形成（4倍）和耗尽GSH（65%）。N-乙酰半胱氨酸或过氧化氢酶限制胡桃醌/抗坏血酸介导的作用，突出了氧化应激在胡桃醌细胞毒性中的作用。胡桃醌单独或与抗坏血酸结合不会引起半胱天冬酶-3活化或PARP裂解，表明坏死样细胞死亡。抗坏血酸可增强胡桃醌引起的DNA损伤和轻微的内质网应激。在用胡桃醌（1-5 μ M）处理的细胞中，观察到细胞增殖的浓度依赖性降低。抗坏血酸不损害细胞增殖，但它与胡桃醌导致克隆性死亡状态。抗坏血酸处理的细胞的运动性不受影响。胡桃醌轻微限制运动，但细胞失去了迁移的能力，最明显的是当处理胡桃醌加抗坏血酸。我们推测胡桃醌通过抑制细胞增殖和T24细胞运动的坏死样机制杀死细胞。这些效果在抗坏血酸盐的存在下增强。(C)2012 Elsevier Inc. All rights reserved.
The effects of juglone on T24 cells were assessed in the presence and absence of ascorbate. The EC50 value for juglone at 24 h decreased from 28.5 mu M to 6.3 mu M in the presence of ascorbate. In juglone-treated cells, ascorbate increased ROS formation (4-fold) and depleted GSH (65%). N-acetylcysteine or catalase restricted the juglone/ascorbate-mediated effects, highlighting the role of oxidative stress in juglone cytotoxicity. Juglone alone or associated with ascorbate did not cause caspase-3 activation or PARP cleavage, suggesting necrosis-like cell death. DNA damage and the mild ER stress caused by juglone were both enhanced by ascorbate. In cells treated with juglone (1-5 mu M), a concentration-dependent decrease in cell proliferation was observed. Ascorbate did not impair cell proliferation but its association with juglone led to a clonogenic death state. The motility of ascorbate-treated cells was not affected. Juglone slightly restricted motility, but cells lost their ability to migrate most noticeably when treated with juglone plus ascorbate. We postulate that juglone kills cells by a necrosis-like mechanism inhibiting cell proliferation and the motility of T24 cells. These effects are enhanced in the presence of ascorbate. (C) 2012 Elsevier Inc. All rights reserved.