{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T18:51:17Z","timestamp":1774896677830,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["UIDB\/04138\/2020"],"award-info":[{"award-number":["UIDB\/04138\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["UIDP\/04138\/2020"],"award-info":[{"award-number":["UIDP\/04138\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["2020.04602.BD"],"award-info":[{"award-number":["2020.04602.BD"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["UIDP\/04567\/2020"],"award-info":[{"award-number":["UIDP\/04567\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["UIDB\/04567\/2020"],"award-info":[{"award-number":["UIDB\/04567\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Manganese(III) porphyrin MnTnBuOE-2-PyP5+ (MnBuOE, BMX-001) is a third-generation redox-active cationic substituted pyridylporphyrin-based drug with a good safety\/toxicity profile that has been studied in several types of cancer. It is currently in four phase I\/II clinical trials on patients suffering from glioma, head and neck cancer, anal squamous cell carcinoma and multiple brain metastases. There is yet an insufficient understanding of the impact of MnBuOE on lung cancer. Therefore, this study aims to fill this gap by demonstrating the effects of MnBuOE on non-small cell lung cancer (NSCLC) A549 and H1975 cell lines. The cytotoxicity of MnBuOE alone or combined with cisplatin was evaluated by crystal violet (CV) and\/or 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-Tetrazolium (MTS) reduction assays. Intracellular ROS levels were assessed using two fluorescent probes. Furthermore, the impact of MnBuOE alone or in combination with cisplatin on collective cell migration, individual chemotactic migration and chemoinvasion was assessed using the wound-healing and transwell assays. The expression of genes related to migration and invasion was assessed through RT-qPCR. While MnBuOE alone decreased H1975 cell viability at high concentrations, when combined with cisplatin it markedly reduced the viability of the more invasive H1975 cell line but not of A549 cell line. However, MnBuOE alone significantly decreased the migration of both cell lines. The anti-migratory effect was more pronounced when MnBuOE was combined with cisplatin. Finally, MnBuOE alone or combined with cisplatin significantly reduced cell invasion. MnBuOE alone or combined with cisplatin downregulated MMP2, MMP9, VIM, EGFR and VEGFA and upregulated CDH1 in both cell lines. Overall, our data demonstrate the anti-metastatic potential of MnBuOE for the treatment of NSCLC.<\/jats:p>","DOI":"10.3390\/cancers15153814","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T02:08:00Z","timestamp":1690510080000},"page":"3814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Redox-Active Manganese(III) Porphyrin, MnTnBuOE-2-PyP5+, Impairs the Migration and Invasion of Non-Small Cell Lung Cancer Cells, Either Alone or Combined with Cisplatin"],"prefix":"10.3390","volume":"15","author":[{"given":"Rita B.","family":"Soares","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (imed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"},{"name":"Lung Unit, Champalimaud Clinical Centre, Champalimaud Foundation, Av. Bras\u00edlia, 1400-038 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-0178","authenticated-orcid":false,"given":"Rita","family":"Manguinhas","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (imed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5604-6142","authenticated-orcid":false,"given":"Jo\u00e3o G.","family":"Costa","sequence":"additional","affiliation":[{"name":"Universidade Lus\u00f3fona\u2019s Research Center for Biosciences & Health Technologies (CBIOS), Campo Grande 376, 1749-024 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1333-9137","authenticated-orcid":false,"given":"Nuno","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Universidade Lus\u00f3fona\u2019s Research Center for Biosciences & Health Technologies (CBIOS), Campo Grande 376, 1749-024 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6567-8379","authenticated-orcid":false,"given":"Nuno","family":"Gil","sequence":"additional","affiliation":[{"name":"Lung Unit, Champalimaud Clinical Centre, Champalimaud Foundation, Av. Bras\u00edlia, 1400-038 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0817-3400","authenticated-orcid":false,"given":"Rafael","family":"Rosell","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, Institute for Health Science Research Germans Trias I Pujol (IGTP), Campus Can Ruti, Ctra de Can Ruti, Cam\u00ed de les Escoles, s\/n, 08916 Badalona, Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-5338","authenticated-orcid":false,"given":"S\u00e9rgio P.","family":"Cam\u00f5es","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (imed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8037-1861","authenticated-orcid":false,"given":"Ines","family":"Batinic-Haberle","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Duke University School of Medicine, Durham, NC 27710, USA"}]},{"given":"Ivan","family":"Spasojevic","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"PK\/PD Core Laboratory, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA"}]},{"given":"Matilde","family":"Castro","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (imed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7804-4068","authenticated-orcid":false,"given":"Joana P.","family":"Miranda","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (imed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7395-5700","authenticated-orcid":false,"given":"Paula","family":"Guedes de Pinho","sequence":"additional","affiliation":[{"name":"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"},{"name":"UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6350-0641","authenticated-orcid":false,"given":"Ana S.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Universidade Lus\u00f3fona\u2019s Research Center for Biosciences & Health Technologies (CBIOS), Campo Grande 376, 1749-024 Lisboa, Portugal"}]},{"given":"Nuno G.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (imed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. 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