The heterocyclic ruthenium(III) complex KP1019 (FFC14A) causes DNA damage and oxidative stress in colorectal tumor cells
The heterocyclic ruthenium(III) complex KP1019 (FFC14A) causes DNA damage and oxidative stress in colorectal tumor cells
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DOI：
10.1016/j.canlet.2005.01.002
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发表时间：
2005-08-26
期刊：
影响因子：
9.7
通讯作者：
Marian, B
中科院分区：
文献类型：
--
作者：
Kapitza, S;Jakupec, MA;Marian, B
Ru（III）配合物KP 1019以剂量依赖性方式诱导结直肠肿瘤细胞中H2 O2的形成。如果仅使尾长微弱加倍至55.87 +/- 3.97 μ m，它也引起DNA链断裂。这两种作用都被5 mM N-乙酰半胱氨酸（NAG）所阻止，NAG也降低了细胞毒性（IC 50 55 vs 30 μ M，无NAC）。63.4 +/- 2.1%的人群线粒体膜电位丧失和聚（ADP-核糖）聚合酶（PARP）的半胱天冬酶依赖性切割显示细胞凋亡诱导。这两种作用都被NAC抑制，NAC将具有去极化线粒体膜的群体减少至24.1 +/- 1.2%，并阻止PARP裂解，表明氧化应激在KP 1019诱导的细胞凋亡中起核心作用。(C)2005爱思唯尔爱尔兰有限公司保留所有权利。
The Ru(III) complex salt KP1019 induced formation of H2O2 in colorectal tumor cells in a dose-dependent way. It also caused DNA-strand breaks if only weakly doubling tail length to 55.87 +/- 3.97 mu m. Both effects were prevented by 5 mM N-acetylcysteine (NAG) which also reduced cytotoxicity (IC50 55 vs 30 mu M without NAC). Induction of apoptosis was show by loss of mitochondrial membrane potential in 63.4 +/- 2.1% of the population and by caspase-dependent cleavage of poly-(ADP-ribose)-polymerase (PARP). Both effects were inhibited by NAC which reduced the population with depolarized mitochondrial membranes to 24.1 +/- 1.2% and prevented PARP-cleavage indicating a central role oxidative stress in KP1019-induced apoptosis. (C) 2005 Elsevier Ireland Ltd. All rights reserved.