8-Hydroxyquinoline ruthenium(II) complexes induce ferroptosis in HeLa cells by down-regulating GPX4 and ferritin

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry Pub Date : 2023-11-01 DOI:10.1016/j.jinorgbio.2023.112365

Minying Huang , Yuqing Zhang , Yao Gong , Zhijun Liang , Xide Chen , Yunxin Ni , Xinjie Pan , Wei Wu , Jiaxi Chen , Zunnan Huang , Jing Sun

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Abstract

Ruthenium complexes are one of the most promising anticancer drugs triggered extensive research. Here, the synthesis and characterization of two ruthenium(II) polypyridine complexes containing 8-hydroxylquinoline as ligand, [Ru(dip)₂(8HQ)]PF₆ (Ru1), [Ru(dpq)₂(8HQ)]PF₆ (Ru2) (8HQ = 8-hydroxylquinoline; dip = 4,7-diphenyl-1,10-phenanthroline; dpq = pyrazino[2,3-f][1,10]phenanthroline) were reported. On the basis of cytotoxicity tests, Ru1 (IC₅₀ = 1.98 ± 0.02 μM) and Ru2 (IC₅₀ = 10.02 ± 0.19 μM) both showed good anticancer activity in a panel of cell lines, especially in HeLa cells. Researches on mechanism indicated that Ru1 and Ru2 acted on mitochondria and nuclei and induced reactive oxygen species (ROS) accumulation, while the morphology of nuclei and cell cycle had no significant change. Western blot assay further proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in HeLa cells. In addition, the toxicity test of zebrafish embryos showed that the concentrations of Ru1 and Ru2 below 120 μM and 60 μM were safe and did not have obvious effect on the normal development of zebrafish embryos.

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8-羟基喹啉钌（II）配合物通过下调GPX4和铁蛋白在HeLa细胞中诱导脱铁性贫血。

钌配合物是最有前景的抗癌药物之一，引发了广泛的研究。本文报道了两种以8-羟基喹啉为配体的钌（II）多吡啶配合物[Ru（dip）2（8HQ）]PF6（Ru1）、[Ru（dpq）2（8 HQ）]PF 6（Ru2）（8HQ=8-羟基喹啉；dip=4,7-二苯基-1,10-菲咯啉；dpq=吡嗪并[2,3-f][1,10]菲咯啉）的合成和表征。在细胞毒性测试的基础上，Ru1（IC50=1.98±0.02μM）和Ru2（IC50=10.02±0.19μM）在一组细胞系中都显示出良好的抗癌活性，尤其是在HeLa细胞中。机制研究表明，Ru1和Ru2作用于线粒体和细胞核，诱导活性氧（ROS）积累，而细胞核形态和细胞周期没有显著变化。Western印迹分析进一步证明GPX4和Ferritin被下调，最终引发HeLa细胞的脱铁性贫血。此外，对斑马鱼胚胎的毒性试验表明，Ru1和Ru2在120μM和60μM以下的浓度是安全的，对斑马鱼胚胎的正常发育没有明显影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Inorganic Biochemistry 生物-生化与分子生物学

CiteScore

7.00

自引率

10.30%

发文量

336

审稿时长

41 days

期刊介绍： The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.