Necroptosis induced by ruthenium (II) complexes as mitochondrial disruptors
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Títol
Necroptosis induced by ruthenium (II) complexes as mitochondrial disruptorsAutoria
Data de publicació
2024-05-28Editor
Springer NatureISSN
2058-7716Cita bibliogràfica
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-zTipus de document
info:eu-repo/semantics/articleVersió
info:eu-repo/semantics/publishedVersionParaules clau / Matèries
Resum
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 ... [+]
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. [-]
Publicat a
Cell Death Discovery (2024) 10:261Dades relacionades
https://static-content.springer.com/esm/art%3A10.1038%2Fs41420-024-02033-z/MediaObjects/41420_2024_2033_MOESM1_ESM.docxEntitat finançadora
Fundação para a Ciência e Tecnologia | La Caixa Foundation | MCIN/AEI/ 10.13039/501100011033
Codi del projecte o subvenció
PTDC/MED-FAR/3492/2021 | CMPR, PTDC/MED-QUI/31468/2017 to PF | 2022.07857.PTDC to RM | LCF/PR/HR21/52410028 to CMPR | UIDB/00645/2020 | UIDP/00645/2020 | RYC2020-028936-I
Títol del projecte o subvenció
ESF Investing in your future
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© The Author(s) 2024
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
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