一种光活性的铂（IV）抗癌配合物通过诱导蛋白质氧化来抑制硫氧还蛋白-硫氧还蛋白还原酶系统的活性。
A Photoactive Platinum(IV) Anticancer Complex Inhibits Thioredoxin-Thioredoxin Reductase System Activity by Induced Oxidization of the Protein.
机构信息
College of Chemistry and Materials Science, Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Laboratory of Molecular-Based Materials , Anhui Normal University , Wuhu 241000 , People's Republic of China.
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry , Chinese Academy of Sciences , Beijing , 100190 , People's Republic of China.
出版信息
Inorg Chem. 2018 May 7;57(9):5575-5584. doi: 10.1021/acs.inorgchem.8b00529. Epub 2018 Apr 24.
Thioredoxin (Trx) is an important enzyme in the redox signaling pathway and is usually overexpressed in tumor cells. We demonstrate herein that the photoactive platinum(IV) anticancer complex trans,trans,trans-[Pt(N)(OH)(Py)] (1) can bind to His, Glu, and Gln residues of Trx upon the irradiation of blue light. More importantly, complex 1 can also induce the oxidation of Met, Trp, and the Cys catalytic sites to form disulfide bonds by generating reactive oxygen species (ROS) upon photoactivation. These eventually lead to inhibition of activity of Trx enzyme and the Trx system and further increase in the cellular ROS level. We speculate that the oxidative damage not only inhibits Trx activity but also greatly contributes to the anticancer action of complex 1.
硫氧还蛋白（Trx）是氧化还原信号通路中的一种重要酶，通常在肿瘤细胞中过度表达。我们在此证明，光活性铂（IV）抗癌配合物反式，反式，反式-[Pt（N）（OH）（Py）]（1）可以在蓝光照射下与 Trx 的 His、Glu 和 Gln 残基结合。更重要的是，配合物 1 还可以通过光激活生成活性氧（ROS）来诱导 Met、Trp 和 Cys 催化位点的氧化，形成二硫键。这最终导致 Trx 酶和 Trx 系统的活性受到抑制，细胞内 ROS 水平进一步升高。我们推测，氧化损伤不仅抑制了 Trx 的活性，而且对配合物 1 的抗癌作用也有很大贡献。
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