Necroptosis induced by ruthenium (II) complexes as mitochondrial disruptors
![Thumbnail](/xmlui/bitstream/handle/10234/207839/gon%c3%a7alves_2024_necro.pdf.jpg?sequence=4&isAllowed=y)
View/ Open
Impact
![Google Scholar](/xmlui/themes/Mirage2/images/uji/logo_google.png)
![Microsoft Academico](/xmlui/themes/Mirage2/images/uji/logo_microsoft.png)
Metadata
Show full item recordcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/33596
comunitat-uji-handle3:10234/33597
comunitat-uji-handle4:
INVESTIGACIONMetadata
Title
Necroptosis induced by ruthenium (II) complexes as mitochondrial disruptorsAuthor (s)
Date
2024-05-28Publisher
Springer NatureISSN
2058-7716Bibliographic 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-zType
info:eu-repo/semantics/articleVersion
info:eu-repo/semantics/publishedVersionSubject
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 ... [+]
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. [-]
Is part of
Cell Death Discovery (2024) 10:261Funder Name
Fundação para a Ciência e Tecnologia | La Caixa Foundation | MCIN/AEI/ 10.13039/501100011033
Project code
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
Project title or grant
ESF Investing in your future
Rights
© The Author(s) 2024
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
This item appears in the folowing collection(s)
- IUPA_Articles [309]