| Autor: |
Soares RB; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal., Manguinhas R; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal., Costa JG; Universidade Lusófona's Research Center for Biosciences & Health Technologies (CBIOS), Campo Grande 376, 1749-024 Lisboa, Portugal., Saraiva N; Universidade Lusófona's Research Center for Biosciences & Health Technologies (CBIOS), Campo Grande 376, 1749-024 Lisboa, Portugal., Gil N; Lung Unit, Champalimaud Clinical Centre, Champalimaud Foundation, Av. Brasília, 1400-038 Lisbon, Portugal., Rosell R; Laboratory of Cellular and Molecular Biology, Institute for Health Science Research Germans Trias i Pujol (IGTP), Campus Can Ruti, Ctra de Can Ruti, Camí de les Escoles, s/n, 08916 Badalona, Barcelona, Spain., Camões SP; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal., Batinic-Haberle I; Department of Radiation Oncology, Duke University School of Medicine, Durham, NC 27710, USA., Spasojevic I; Department of Medicine, Duke University School of Medicine and PK/PD Core Laboratory, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA., Castro M; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal., Miranda JP; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal., Amaro F; Associate Laboratory i4HB-Institute for Health and Bioeconomy, Department of Biological Sciences, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.; UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal., Pinto J; Associate Laboratory i4HB-Institute for Health and Bioeconomy, Department of Biological Sciences, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.; UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal., Fernandes AS; Universidade Lusófona's Research Center for Biosciences & Health Technologies (CBIOS), Campo Grande 376, 1749-024 Lisboa, Portugal., Guedes de Pinho P; Associate Laboratory i4HB-Institute for Health and Bioeconomy, Department of Biological Sciences, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.; UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal., Oliveira NG; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal. |
| Abstrakt: |
The manganese(III) porphyrin MnTnHex-2-PyP 5+ (MnTnHex) is a potent superoxide dismutase mimic and modulator of redox-based transcriptional activity that has been studied in the context of different human disease models, including cancer. Nevertheless, for lung cancer, hardly any information is available. Thus, the present work aims to fill this gap and reports the effects of MnTnHex in non-small cell lung cancer (NSCLC) cells, more specifically, A549 and H1975 cells, in vitro. Both cell lines were initially characterized in terms of innate levels of catalase, glutathione peroxidase 1, and peroxiredoxins 1 and 2. To assess the effect of MnTnHex in NSCLC, alone or in combination with cisplatin, endpoints related to the cell viability, cell cycle distribution, cell motility, and characterization of the volatile carbonyl compounds (VCCs) generated in the extracellular medium (i.e., exometabolome) were addressed. The results show that MnTnHex as a single drug markedly reduced the viability of both NSCLC cell lines, with some IC 50 values reaching sub-micromolar levels. This redox-active drug also altered the cell cycle distribution, induced cell death, and increased the cytotoxicity pattern of cisplatin. MnTnHex also reduced collective cell migration. Finally, the metabolomics study revealed an increase in the levels of a few VCCs associated with oxidative stress in MnTnHex-treated cells. Altogether these results suggest the therapeutic potential of MnTnHex to be further explored, either alone or in combination therapy with cisplatin, in NSCLC. |
