Antitumor Activity of Mitochondrial Uncouplers Based on Platinum (II) N-Heterocyclic Carbene Complexes.

IF 3 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Biochemistry and Biophysics Pub Date : 2026-09-25 DOI:10.1007/s12013-026-02181-2

Vsevolod V Melekhin, Maria D Tokhtueva, Anna E Chernysheva, Danil V Andreev, Svetlana M Podergina, Anastasia V Paramonova, Oleg G Makeev, Vladislav M Abramov, Oleg S Eltsov

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Abstract

In the present study, the effects of mitochondrial uncouplers on lung carcinoma cells were investigated. The compounds were found to inhibit cell proliferation by inducing cell cycle arrest at the G1/S transition. Treatment with the tested complexes led to acidification of the extracellular medium, associated with enhanced lactate production due to compensatory increase in glycolytic flux. The effect on HIF signalling has been demonstrated, which is especially intriguing when considering how to overcome neoplastic cells' resistance to chemical agents. Signaling pathway analysis revealed that mitochondrial uncoupling increased ERK1/2 phosphorylation levels, which may represent a compensatory cellular response to energy stress. Exposure to the complexes also resulted in elevated reactive oxygen species (ROS) generation and pronounced morphological alterations. These findings provide further insight into the mechanisms of action of mitochondrial uncouplers and their impact on proliferation, metabolism, and signaling pathways in tumor cells.

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基于铂（II） n -杂环卡宾配合物的线粒体解偶联剂抗肿瘤活性研究。

本研究探讨了线粒体解偶联剂对肺癌细胞的影响。发现这些化合物通过在G1/S过渡时诱导细胞周期阻滞来抑制细胞增殖。用测试的复合物处理导致细胞外培养基酸化，由于糖酵解通量的代偿性增加，乳酸产量增加。对HIF信号传导的影响已经被证明，当考虑如何克服肿瘤细胞对化学试剂的抗性时，这一点尤其有趣。信号通路分析显示，线粒体解偶联增加了ERK1/2磷酸化水平，这可能代表了细胞对能量应激的代偿反应。暴露于这些复合物也导致活性氧（ROS）的产生升高和明显的形态改变。这些发现进一步揭示了线粒体解偶联剂的作用机制及其对肿瘤细胞增殖、代谢和信号通路的影响。

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

Cell Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

7.5 months

期刊介绍： Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.