Antagonistic effect of a nitric oxide donor agents based on ruthenium complex combined with cisplatin on lung tumor cell lines

IF 3.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nitric oxide : biology and chemistry Pub Date : 2025-05-31 DOI:10.1016/j.niox.2025.05.009

Angelica E. Graminha , Amanda B. Becceneri , Rafaella R Rios , Márcia Regina Cominetti , Juliana Cristina Biazzotto , Roberto Santana da Silva

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引用次数: 0

Abstract

Nitric oxide (NO) is a versatile biological messenger involved in numerous physiological processes and anticancer mechanisms. Its functions are highly dependent on its concentration and the specific site of action. In this study, we investigated the effects of controlled NO release mediated by ruthenium-based compounds. The tests demonstrated the significant potential of combining cisplatin with the non-cytotoxic ruthenium nitrosyl complexes cis-[Ru(bpy)₂(NO₂)(solv)]PF₆ and cis-Ru(bpy)₂(NO)(pic)](PF₆)₃, where bpy = 2,2′-bipyridine ,pic = 4-picoline and solv = solvent. This combination increased selectivity between non-tumoral and tumoral lung cells (MRC-5/A549) compared to the selectivity index of cisplatin alone. These nitrosyl complexes exhibited an antagonistic interaction with cisplatin, reducing its cytotoxic efficacy. Cell cycle and apoptosis assays revealed that the cisplatin/Ru combination more effectively inhibited cisplatin's cytotoxic effect on the MRC-5 non-tumoral lung cell line compared to the A549 tumoral cell line. Morphological assays conducted in 3D culture with the cis-[Ru(bpy)₂(NO)(pic)](PF₆)₃ complex confirmed its chemopreventive behavior, as the 3D system closely mimics in vivo conditions. Moreover, the absence of cytotoxicity in these ruthenium nitrosyl complexes highlights their potential as promising candidates for adjuvant therapy in combination with other drugs.

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钌络合物联合顺铂的一氧化氮供体对肺肿瘤细胞系的拮抗作用。

一氧化氮（NO）是一种多用途的生物信使，参与许多生理过程和抗癌机制。它的功能高度依赖于它的浓度和特定的作用部位。在这项研究中，我们研究了钌基化合物介导的控制NO释放的影响。试验表明，顺铂与无细胞毒性的钌亚硝基配合物顺式-[Ru(bpy)2(NO2)(solv)]PF6和顺式-Ru(bpy)2(NO)(pic)](PF6)3结合具有显著的潜力，其中bpy = 2,2'-联吡啶，pic = 4-吡啶（顺铂/Ru）。与单用顺铂的选择性指数相比，联合用药增加了非肿瘤和肿瘤肺细胞（MRC-5/A549）之间的选择性。这些亚硝基复合物表现出与顺铂的拮抗相互作用，降低其细胞毒性作用。细胞周期和凋亡实验显示，与A549肿瘤细胞系相比，顺铂/Ru联合治疗更有效地抑制顺铂对MRC-5非肿瘤肺细胞系的细胞毒作用。用顺式-[Ru(bpy)2(NO)(pic)](PF6)3配合物在三维培养中进行的形态学分析证实了其化学预防作用，因为三维系统非常接近体内条件。此外，这些钌亚硝基络合物没有细胞毒性，突出了它们作为与其他药物联合辅助治疗的有希望的候选者的潜力。

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

Nitric oxide : biology and chemistry 生物-生化与分子生物学

CiteScore

7.50

自引率

7.70%

发文量

审稿时长

52 days

期刊介绍： Nitric Oxide includes original research, methodology papers and reviews relating to nitric oxide and other gasotransmitters such as hydrogen sulfide and carbon monoxide. Special emphasis is placed on the biological chemistry, physiology, pharmacology, enzymology and pathological significance of these molecules in human health and disease. The journal also accepts manuscripts relating to plant and microbial studies involving these molecules.