Ru(II)-based complexes containing 2-thiouracil derivatives suppress liver cancer stem cells by targeting NF-κB and Akt/mTOR signaling.

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Autor(es): dc.creatorBomfim, Larissa Mendes-
Autor(es): dc.creatorNeves, Sara Parente-
Autor(es): dc.creatorCoelho, Amanda M. R. M.-
Autor(es): dc.creatorNogueira, Mateus L.-
Autor(es): dc.creatorDias, Rosane Borges-
Autor(es): dc.creatorValverde, Ludmila de Faro-
Autor(es): dc.creatorRocha, Clarissa Araújo Gurgel-
Autor(es): dc.creatorSoares, Milena Botelho Pereira-
Autor(es): dc.creatorBatista, Alzir Azevedo-
Autor(es): dc.creatorCorrea, Rodrigo de Souza-
Autor(es): dc.creatorBezerra, Daniel Pereira-
Data de aceite: dc.date.accessioned2025-08-21T15:03:40Z-
Data de disponibilização: dc.date.available2025-08-21T15:03:40Z-
Data de envio: dc.date.issued2025-03-20-
Data de envio: dc.date.issued2023-
Fonte completa do material: dc.identifierhttps://www.repositorio.ufop.br/handle/123456789/19984-
Fonte completa do material: dc.identifierhttps://doi.org/10.1038/s41420-024-02036-w-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/1001720-
Descrição: dc.descriptionCancer stem cells (CSCs) are defined as a rare population of cancer cells related to tumor initiation and maintenance. These cells are primarily responsible for tumor growth, invasion, metastasis, recurrence, and resistance to chemotherapy. In this paper, we demonstrated the ability of Ru(II)-based complexes containing 2-thiouracil derivatives with the chemical formulas trans-[Ru(2TU) (PPh3)2(bipy)]PF6 (1) and trans-[Ru(6m2TU)(PPh3)2(bipy)]PF6 (2) (where 2TU = 2-thiouracil and 6m2TU = 6-methyl-2-thiouracil) to suppress liver CSCs by targeting NF-κB and Akt/mTOR signaling. Complexes 1 and 2 displayed potent cytotoxic effects on cancer cell lines and suppressed liver CSCs from HepG2 cells. Increased phosphatidylserine exposure, loss of mitochondrial transmembrane potential, increased PARP (Asp214) cleavage, DNA fragmentation, chromatin condensation and cytoplasmic shrinkage were detected in HepG2 cells treated with these complexes. Mechanistically, complexes 1 and 2 target NF-κB and Akt/mTOR signaling in HepG2 cells. Cell motility inhibition was also detected in HepG2 cells treated with these complexes. Complexes 1 and 2 also inhibited tumor progression in mice with HepG2 cell xenografts and exhibited tolerable systemic toxicity. Taken together, these results indicate that these complexes are new anti-HCC drug candidates that can suppress liver CSCs.-
Formato: dc.formatapplication/pdf-
Idioma: dc.languageen-
Direitos: dc.rightsaberto-
Direitos: dc.rightsThis article is under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. Fonte: PDF do artigo.-
Título: dc.titleRu(II)-based complexes containing 2-thiouracil derivatives suppress liver cancer stem cells by targeting NF-κB and Akt/mTOR signaling.-
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