Gold(III) - Dithiocarbamato complexes induce cancer cell death triggered by thioredoxin redox system inhibition and activation of ERK pathway
Gold(III) - Dithiocarbamato complexes induce cancer cell death triggered by thioredoxin redox system inhibition and activation of ERK pathway
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DOI：
10.1016/j.chembiol.2007.08.016
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发表时间：
2007-10-01
影响因子：
--
通讯作者：
Bindoli, Alberto
中科院分区：
文献类型：
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作者：
Saggioro, Daniela;Rigobello, Maria Pia;Bindoli, Alberto
虽然金化合物现在被认为是有前途的抗癌剂，但迄今为止仅研究了用于此目的的金（I）衍生物，而金（III）络合物的使用由于其在生理条件下的差的稳定性而受到阻碍。因此，我们已经进行了研究选定的金（III）抗癌剂，由于螯合二硫代氨基甲酸酯配体的存在下，表现出增强的稳定性。我们发现它们通过凋亡和非凋亡机制诱导癌细胞死亡。它们还抑制硫氧还蛋白还原酶活性，产生自由基，修饰一些线粒体功能，并增加ERK 1/2磷酸化。基于我们的研究结果，我们提出并讨论了一个工作模型，表明解除管制的硫氧还蛋白还原酶/硫氧还蛋白氧化还原系统是一个主要的机制，参与研究的金（III）-dithiocarbamato配合物的抗癌活性。
Although gold compounds are now recognized as promising anticancer agents, so far only gold(I) derivatives have been investigated for this purpose, whereas the use of gold(III) complexes has been hampered by their poor stability under physiological conditions. We have therefore carried out studies on selected gold(III) anticancer agents, showing enhanced stability due to the presence of chelating dithiocarbamato ligands. We found that they induce cancer cell death through both apoptotic and nonapoptotic mechanisms. They also inhibit thioredoxin reductase activity, generate free radicals, modify some mitochondrial functions, and increase ERK1/2 phosphorylation. Based on our results, we propose and discuss a working model suggesting that deregulation of the thioredoxin reductase/thioredoxin redox system is a major mechanism involved in the anticancer activity of the investigated gold(III)-dithiocarbamato complexes.