| Author | Costa, Rafaela G. A. | |
| Author | Oliveira, Maiara de S. | |
| Author | Rodrigues, Ana Carolina B. da C. | |
| Author | Silva, Suellen L. R. | |
| Author | Dias, Ingrid R. S. B. | |
| Author | Soares, Milena B. P. | |
| Author | Valverde, Ludmila de Faro | |
| Author | Rocha, Clarissa Araújo Gurgel | |
| Author | Dias, Rosane Borges | |
| Author | Bezerra, Daniel P. | |
| Access date | 2024-05-17T15:22:30Z | |
| Available date | 2024-05-17T15:22:30Z | |
| Document date | 2024 | |
| Citation | COSTA, Rafaela G. A. et al. Bortezomib suppresses acute myelogenous leukaemia stem-like KG-1ª cells via NF-κB inhibition and the induction of oxidative stress. Journal of Cellular and Molecular Medicine, v. 28, n.8, p. 1-10, 2024. | en_US |
| ISSN | 1582-4934 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/64115 | |
| Sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
Fundação Oswaldo Cruz (FIOCRUZ).
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). | en_US |
| Language | eng | en_US |
| Publisher | Wiley Open Access | en_US |
| Rights | open access | en_US |
| Subject in Portuguese | AML | en_US |
| Subject in Portuguese | Bortezomib | en_US |
| Subject in Portuguese | Células-tronco leucêmicas | en_US |
| Subject in Portuguese | NF-κB | en_US |
| Subject in Portuguese | Estresse oxidativo | en_US |
| Title | Bortezomib suppresses acute myelogenous leukaemia stem-like KG-1a cells via NF-κB inhibition and the induction of oxidative stress | en_US |
| Type | Article | en_US |
| DOI | 10.1111/jcmm.18333 | |
| Abstract | Acute myelogenous leukaemia (AML) originates and is maintained by leukaemic stem cells (LSCs) that are inherently resistant to antiproliferative therapies, indicating that a critical strategy for overcoming chemoresistance in AML therapy is to eradicate LSCs. In this work, we investigated the anti-AML activity of bortezomib (BTZ), emphasizing its anti-LSC potential, using KG-1a cells, an AML cell line with stem-like properties. BTZ presented potent cytotoxicity to both solid and haematological malignancy cells and reduced the stem-like features of KG-1a cells, as observed by the reduction in CD34- and CD123-positive cells. A reduction in NF-κB p65 nuclear staining was observed in BTZ-treated KG-1a cells, in addition to upregulation of the NF-κB inhibitor gene NFΚBIB. BTZ-induced DNA fragmentation, nuclear condensation, cell shrinkage and loss of transmembrane mitochondrial potential along with an increase in active caspase-3 and cleaved PARP-(Asp 214) level in KG-1a cells. Furthermore, BTZ-induced cell death was partially prevented by pretreatment with the pancaspase inhibitor Z-VAD-(OMe)-FMK, indicating that BTZ induces caspase-mediated apoptosis. BTZ also increased mitochondrial superoxide levels in KG-1a cells, and BTZ-induced apoptosis was partially prevented by pretreatment with the antioxidant N-acetylcysteine, indicating that BTZ induces oxidative stress-mediated apoptosis in KG-1a cells. At a dosage of 0.1 mg/kg every other day for 2 weeks, BTZ significantly reduced the percentage of hCD45-positive cells in the bone marrow and peripheral blood of NSG mice engrafted with KG-1a cells with tolerable toxicity. Taken together, these data indicate that the anti-LSC potential of BTZ appears to be an important strategy for AML treatment. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto SENAI de Inovação em Sistemas Avançados de Saúde. SENAI CIMATEC. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Odontologia. Departamento de Propedêutica. Salvador, BA, Brasil / Instituto D'Or de Pesquisa e Ensino (IDOR). Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Odontologia. Departamento de Propedêutica. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Subject | AML | en_US |
| Subject | Bortezomib | en_US |
| Subject | Leukaemic stem cells | en_US |
| Subject | NF-κB | en_US |
| Subject | Oxidative stress | en_US |
| DeCS | Bortezomib | en_US |
| DeCS | Células-tronco neoplásicas | en_US |
| DeCS | Estresse oxidativo | en_US |
