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

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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.

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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。

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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.

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