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Necroptosis induced by ruthenium (II) complexes as mitochondrial disruptors
dc.contributor.author | Gonçalves, Joana | |
dc.contributor.author | Amaral, Joana | |
dc.contributor.author | Capela, Rita | |
dc.contributor.author | Perry, Maria Jesus | |
dc.contributor.author | Braga, Cláudia | |
dc.contributor.author | Gaspar, Maria Manuela | |
dc.contributor.author | Piedade, M. Fatima | |
dc.contributor.author | Bijlsma, Lubertus | |
dc.contributor.author | Roig-Navarro, Antoni F. | |
dc.contributor.author | Pinto, Sandra N. | |
dc.contributor.author | Moreira, Rui | |
dc.contributor.author | Florindo, Pedro | |
dc.contributor.author | Rodrigues, Cecília M. P. | |
dc.date.accessioned | 2024-06-18T09:24:28Z | |
dc.date.available | 2024-06-18T09:24:28Z | |
dc.date.issued | 2024-05-28 | |
dc.identifier.citation | Gonçalves, J., Amaral, J.D., Capela, R. et al. Necroptosis induced by ruthenium (II) complexes as mitochondrial disruptors. Cell Death Discov. 10, 261 (2024). https://doi.org/10.1038/s41420-024-02033-z | ca_CA |
dc.identifier.issn | 2058-7716 | |
dc.identifier.uri | http://hdl.handle.net/10234/207839 | |
dc.description.abstract | Inducing necroptosis in cancer cells has emerged as an effective strategy to overcome drug resistance. However, while organic small molecules have been extensively studied for this purpose, metal-based compounds have received relatively little attention as triggers of necroptosis. The development of ruthenium (II) hybrid compounds, particularly those containing triazene (Ru-TRZ), highlights a novel avenue for modulating necroptotic cell death. Here we show that incorporating a methyltriazene moiety, a known alkylating warhead, confers superior mitochondrial-targeting properties and enhances cell death compared to amide-containing counterparts. Ru-hybrid TRZ2 exhibits also antitumor efficacy against in vivo drug-resistant cancer cells. Mechanistically, we demonstrate that Ru-TRZ hybrids induce apoptosis. In addition, by activating downstream RIPK3-driven cell death, TRZ2 proficiently restrains normal mitochondrial function and activity, leading to cancer cell necroptosis. Finally, TRZ2 synergizes anti-proliferative activity and cell death effects induced by conventional drugs. In conclusion, Ru-TRZ2 stands as a promising ruthenium-based chemotherapeutic agent inducing necroptosis in drug resistant cancer cells. | ca_CA |
dc.format.extent | 13 p. | ca_CA |
dc.format.mimetype | application/pdf | ca_CA |
dc.language.iso | eng | ca_CA |
dc.publisher | Springer Nature | ca_CA |
dc.relation | ESF Investing in your future | ca_CA |
dc.relation.isPartOf | Cell Death Discovery (2024) 10:261 | ca_CA |
dc.relation.uri | https://static-content.springer.com/esm/art%3A10.1038%2Fs41420-024-02033-z/MediaObjects/41420_2024_2033_MOESM1_ESM.docx | ca_CA |
dc.rights | © The Author(s) 2024 | ca_CA |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | ca_CA |
dc.subject | drug development | ca_CA |
dc.subject | screening | ca_CA |
dc.title | Necroptosis induced by ruthenium (II) complexes as mitochondrial disruptors | ca_CA |
dc.type | info:eu-repo/semantics/article | ca_CA |
dc.identifier.doi | https://doi.org/10.1038/s41420-024-02033-z | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_CA |
dc.type.version | info:eu-repo/semantics/publishedVersion | ca_CA |
project.funder.name | Fundação para a Ciência e Tecnologia | ca_CA |
project.funder.name | La Caixa Foundation | ca_CA |
project.funder.name | MCIN/AEI/ 10.13039/501100011033 | ca_CA |
oaire.awardNumber | PTDC/MED-FAR/3492/2021 | ca_CA |
oaire.awardNumber | CMPR, PTDC/MED-QUI/31468/2017 to PF | ca_CA |
oaire.awardNumber | 2022.07857.PTDC to RM | ca_CA |
oaire.awardNumber | LCF/PR/HR21/52410028 to CMPR | ca_CA |
oaire.awardNumber | UIDB/00645/2020 | ca_CA |
oaire.awardNumber | UIDP/00645/2020 | ca_CA |
oaire.awardNumber | RYC2020-028936-I | ca_CA |
dc.subject.ods | 3. Salud y bienestar | ca_CA |
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