基于氧化还原的癌症治疗策略旨在提高癌细胞中的活性氧（ROS）水平，从而改变其氧化还原状态，并最终诱导细胞死亡。有前途的化合物，称为超氧化物歧化酶模拟物（SODm），例如MnTnHex-2-Py5 (MnTnHex) 可以增加 ROS 清除系统缺陷的癌细胞中的细胞内 H2O2，从而增强放疗和化疗疗效。我们之前已经证明，MnTnHex 单独或与顺铂联合对非小细胞肺癌 (NSCLC) 细胞具有细胞毒性。为了更深入地了解这种化合物的作用和安全性，分析细胞内发生的代谢变化至关重要。因此，我们的目标是使用基于核磁共振 (NMR) 光谱的代谢组学研究 NSCLC 细胞（A549 和 H1975）的细胞内代谢组（细胞内代谢物），以评估暴露于 MnTnHex 本身或与顺铂组合后细胞代谢的变化。 1 H NMR 代谢组学显示，与未处理的细胞相比，单独暴露于 MnTnHex 或与顺铂联合使用的 A549 细胞中显着改变的代谢物数量较多（九种失调代谢物），表明对氨酰基-tRNA 生物合成、糖酵解/糖异生和牛磺酸的影响以及亚牛磺酸、甘油磷脂、丙酮酸、精氨酸和脯氨酸代谢。反过来，在与 MnTnHex 和顺铂共同处理后，H1975 细胞表现出六种代谢物水平的显着变化，表明氨酰基-tRNA 生物合成、精氨酸和脯氨酸代谢、丙酮酸代谢和糖酵解/糖异生发生失调。这些发现有助于我们了解 MnTnHex 对 NSCLC 细胞的影响。重要的是，特定改变的代谢物（例如牛磺酸）可能有助于 MnTnHex 的化学增敏作用。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Redox-based cancer therapeutic strategies aim to raise reactive oxygen species (ROS) levels in cancer cells, thus modifying their redox status, and eventually inducing cell death. Promising compounds, known as superoxide dismutase mimics (SODm), e.g. MnTnHex-2-Py5+ (MnTnHex), could increase intracellular H2O2 in cancer cells with deficient ROS removal systems and therefore enhance radio- and chemotherapy efficacy. We have previously shown that MnTnHex was cytotoxic either alone or combined with cisplatin to non-small cell lung cancer (NSCLC) cells. To gain a deeper understanding of the effects and safety of this compound, it is crucial to analyze the metabolic alterations that take place within the cell. Our goal was thus to study the intracellular metabolome (intracellular metabolites) of NSCLC cells (A549 and H1975) using nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to evaluate the changes in cellular metabolism upon exposure to MnTnHex per se or in combination with cisplatin. 1H NMR metabolomics revealed a higher number of significantly altered metabolites in A549 cells exposed to MnTnHex alone or combined with cisplatin in comparison with non-treated cells (nine dysregulated metabolites), suggesting an impact on aminoacyl-tRNA biosynthesis, glycolysis/gluconeogenesis, and taurine and hypotaurine, glycerophospholipid, pyruvate, arginine and proline metabolisms. In turn, H1975 cells exhibited significant alterations in the levels of six metabolites upon co-treatment with MnTnHex and cisplatin, suggesting dysregulations in aminoacyl-tRNA biosynthesis, arginine and proline metabolism, pyruvate metabolism, and glycolysis/gluconeogenesis. These findings help us understanding the impact of MnTnHex on NSCLC cells. Importantly, specific altered metabolites, such as taurine, may contribute to the chemosensitizing effects of MnTnHex.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.