Impact of the redox-active MnTnHex-2-PyP 5+ and cisplatin on the metabolome of non-small cell lung cancer cells.
Rita B SoaresJoana PintoFilipa AmaroRita ManguinhasNuno GilRafael RosellInes Batinic-HaberleAna S FernandesNuno G OliveiraPaula Guedes de PinhoPublished in: Biochemical pharmacology (2024)
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-Py 5+ (MnTnHex), could increase intracellular H 2 O 2 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. 1 H 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, taurine, hypotaurine, glycerophospholipid, pyruvate, arginine and proline metabolisms. Regarding H1975 cells, significant alterations in the levels of six metabolites were observed 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 to understand the impact of MnTnHex on NSCLC cells. Importantly, specific altered metabolites, such as taurine, may contribute to the chemosensitizing effects of MnTnHex.
Keyphrases
- induced apoptosis
- cell cycle arrest
- cell death
- reactive oxygen species
- magnetic resonance
- ms ms
- small cell lung cancer
- endoplasmic reticulum stress
- oxidative stress
- magnetic resonance imaging
- single cell
- stem cells
- squamous cell carcinoma
- computed tomography
- bone marrow
- high resolution
- cell proliferation
- brain metastases
- hydrogen peroxide
- cell wall