Minying Huang , Yuqing Zhang , Yao Gong , Zhijun Liang , Xide Chen , Yunxin Ni , Xinjie Pan , Wei Wu , Jiaxi Chen , Zunnan Huang , Jing Sun
{"title":"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。","authors":"Minying Huang , Yuqing Zhang , Yao Gong , Zhijun Liang , Xide Chen , Yunxin Ni , Xinjie Pan , Wei Wu , Jiaxi Chen , Zunnan Huang , Jing Sun","doi":"10.1016/j.jinorgbio.2023.112365","DOIUrl":null,"url":null,"abstract":"<div><p><span>Ruthenium<span> 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)</span></span><sub>2</sub>(8HQ)]PF<sub>6</sub> (<strong>Ru1</strong>), [Ru(dpq)<sub>2</sub>(8HQ)]PF<sub>6</sub> (<strong>Ru2</strong><span>) (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, </span><strong>Ru1</strong> (IC<sub>50</sub> = 1.98 ± 0.02 μM) and <strong>Ru2</strong> (IC<sub>50</sub><span> = 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 </span><strong>Ru1</strong> and <strong>Ru2</strong><span><span><span> acted on mitochondria and nuclei and induced reactive oxygen species (ROS) accumulation, while the morphology of nuclei and cell cycle had no significant change. </span>Western blot assay further proved that </span>GPX4<span> and Ferritin<span> were down-regulated, which eventually triggered ferroptosis in HeLa cells. In addition, the toxicity test of zebrafish embryos showed that the concentrations of </span></span></span><strong>Ru1</strong> and <strong>Ru2</strong> below 120 μM and 60 μM were safe and did not have obvious effect on the normal development of zebrafish embryos.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"248 ","pages":"Article 112365"},"PeriodicalIF":3.8000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"8-Hydroxyquinoline ruthenium(II) complexes induce ferroptosis in HeLa cells by down-regulating GPX4 and ferritin\",\"authors\":\"Minying Huang , Yuqing Zhang , Yao Gong , Zhijun Liang , Xide Chen , Yunxin Ni , Xinjie Pan , Wei Wu , Jiaxi Chen , Zunnan Huang , Jing Sun\",\"doi\":\"10.1016/j.jinorgbio.2023.112365\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>Ruthenium<span> 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)</span></span><sub>2</sub>(8HQ)]PF<sub>6</sub> (<strong>Ru1</strong>), [Ru(dpq)<sub>2</sub>(8HQ)]PF<sub>6</sub> (<strong>Ru2</strong><span>) (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, </span><strong>Ru1</strong> (IC<sub>50</sub> = 1.98 ± 0.02 μM) and <strong>Ru2</strong> (IC<sub>50</sub><span> = 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 </span><strong>Ru1</strong> and <strong>Ru2</strong><span><span><span> acted on mitochondria and nuclei and induced reactive oxygen species (ROS) accumulation, while the morphology of nuclei and cell cycle had no significant change. </span>Western blot assay further proved that </span>GPX4<span> and Ferritin<span> were down-regulated, which eventually triggered ferroptosis in HeLa cells. In addition, the toxicity test of zebrafish embryos showed that the concentrations of </span></span></span><strong>Ru1</strong> and <strong>Ru2</strong> below 120 μM and 60 μM were safe and did not have obvious effect on the normal development of zebrafish embryos.</p></div>\",\"PeriodicalId\":364,\"journal\":{\"name\":\"Journal of Inorganic Biochemistry\",\"volume\":\"248 \",\"pages\":\"Article 112365\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2023-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inorganic Biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0162013423002477\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inorganic Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0162013423002477","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
8-Hydroxyquinoline ruthenium(II) complexes induce ferroptosis in HeLa cells by down-regulating GPX4 and ferritin
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.
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.
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