Ruthenium(II)-mercapto complexes induce cell damage via apoptosis pathway on ovarian cancer cells

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Inorganic Biochemistry Pub Date : 2024-12-30 DOI:10.1016/j.jinorgbio.2024.112819

Marcos V. Palmeira-Mello , Tamara Teixeira , Matheus Reis Santos de Melo , Heloiza Diniz Nicolella , Jocely L. Dutra , Marcia R. Cominetti , Fillipe Vieira Rocha , Denise Crispim Tavares , Alzir A. Batista

{"title":"Ruthenium(II)-mercapto complexes induce cell damage via apoptosis pathway on ovarian cancer cells","authors":"Marcos V. Palmeira-Mello , Tamara Teixeira , Matheus Reis Santos de Melo , Heloiza Diniz Nicolella , Jocely L. Dutra , Marcia R. Cominetti , Fillipe Vieira Rocha , Denise Crispim Tavares , Alzir A. Batista","doi":"10.1016/j.jinorgbio.2024.112819","DOIUrl":null,"url":null,"abstract":"<div><div>Ovarian cancer represents a leading cause of cancer-related deaths in women worldwide. Chemotherapeutic agents are usually employed to treat the patients, and Ruthenium(II)-based compounds have been investigated as possible substitutes for platinum drugs. In this work, we studied three different Ru(II)-phosphine-mercapto complexes (<strong>1–3</strong>) as potential cytotoxic agents against A2780 and A2780-<em>cis</em>R ovarian cancer cells. A time-dependent cytotoxicity was observed for <strong>2</strong>, which also exhibited better selectivity than cisplatin control. A similar cytotoxic behavior was observed on 3D tumor spheroids. Although no changes were observed in cell cycle distribution, compound <strong>2</strong> affected the mitochondrial membrane potential on A2780 cells, and caused cell death <em>via</em> apoptotic pathway, which was confirmed by flow cytometry assay. Western blotting experiments revealed that <strong>2</strong> affected the expression of p53, PCNA, γH2AX and cleaved caspase-3, making it a promising anticancer agent for ovarian cancer.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"265 ","pages":"Article 112819"},"PeriodicalIF":3.8000,"publicationDate":"2024-12-30","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/S0162013424003441","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Ovarian cancer represents a leading cause of cancer-related deaths in women worldwide. Chemotherapeutic agents are usually employed to treat the patients, and Ruthenium(II)-based compounds have been investigated as possible substitutes for platinum drugs. In this work, we studied three different Ru(II)-phosphine-mercapto complexes (1–3) as potential cytotoxic agents against A2780 and A2780-cisR ovarian cancer cells. A time-dependent cytotoxicity was observed for 2, which also exhibited better selectivity than cisplatin control. A similar cytotoxic behavior was observed on 3D tumor spheroids. Although no changes were observed in cell cycle distribution, compound 2 affected the mitochondrial membrane potential on A2780 cells, and caused cell death via apoptotic pathway, which was confirmed by flow cytometry assay. Western blotting experiments revealed that 2 affected the expression of p53, PCNA, γH2AX and cleaved caspase-3, making it a promising anticancer agent for ovarian cancer.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

钌(II)-巯基复合物通过凋亡途径诱导卵巢癌细胞损伤。

卵巢癌是全世界妇女癌症相关死亡的主要原因。化疗药物通常用于治疗患者，钌（II）基化合物已被研究作为铂类药物的可能替代品。在这项工作中，我们研究了三种不同的Ru(II)-膦-巯基络合物（1-3）作为抗A2780和A2780- cisr卵巢癌细胞的潜在细胞毒性药物。观察到2的时间依赖性细胞毒性，也表现出比顺铂对照组更好的选择性。在三维肿瘤球体上观察到类似的细胞毒性行为。虽然没有观察到细胞周期分布的变化，但化合物2影响了A2780细胞的线粒体膜电位，并通过凋亡途径引起细胞死亡，流式细胞术实验证实了这一点。Western blotting实验显示，2能影响p53、PCNA、γ - h2ax和cleaved caspase-3的表达，是一种很有前景的卵巢癌抗癌药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

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.

期刊最新文献

Editorial Board Contents continued Graphical abstract TOC Graphical abstract TOC Synthesis, crystal structure, computational and solution studies of a new phosphotetradecavanadate salt. Assessment of its effect on U87 glioblastoma cells