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Emetine induces oxidative stress, cell differentiation and NF-κB inhibition, suppressing AML stem/progenitor cells

Silva, Suellen L R ; Dias, Ingrid R S B ; Rodrigues, Ana Carolina B da C ; Costa, Rafaela G A ; Oliveira, Maiara de S ; Barbosa, Gabriela A da C ; Soares, Milena B P ; Dias, Rosane B ; Valverde, Ludmila F ; Rocha, Clarissa A G ; Roy, Nainita ; Park, Christopher Y ; Bezerra, Daniel P

Cell death discovery, 2024-04, Vol.10 (1), p.201-201 [Periódico revisado por pares]

United States: Springer Nature B.V

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Título:
Emetine induces oxidative stress, cell differentiation and NF-κB inhibition, suppressing AML stem/progenitor cells
Autor: Silva, Suellen L R ; Dias, Ingrid R S B ; Rodrigues, Ana Carolina B da C ; Costa, Rafaela G A ; Oliveira, Maiara de S ; Barbosa, Gabriela A da C ; Soares, Milena B P ; Dias, Rosane B ; Valverde, Ludmila F ; Rocha, Clarissa A G ; Roy, Nainita ; Park, Christopher Y ; Bezerra, Daniel P
Assuntos: Acetylcysteine ; Acute myeloid leukemia ; Antiparasitic agents ; Apoptosis ; Caspase-3 ; CD123 antigen ; CD34 antigen ; CD99 antigen ; Cell death ; Cell differentiation ; Cytotoxicity ; Depolarization ; DNA fragmentation ; Emetine ; Malignancy ; Mitochondrial DNA ; NF-κB protein ; Oxidative stress ; Progenitor cells ; Reactive oxygen species
É parte de: Cell death discovery, 2024-04, Vol.10 (1), p.201-201
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Acute myeloid leukemia (AML) is a fatal malignancy of the blood and bone marrow. Leukemic stem cells (LSCs) are a rare subset of leukemic cells that promote the development and progression of AML, and eradication of LSCs is critical for effective control of this disease. Emetine is an FDA-approved antiparasitic drug with antitumor properties; however, little is known about its potential against LSCs. Herein, we explored the antileukemic potential of emetine, focusing on its effects on AML stem/progenitor cells. Emetine exhibited potent cytotoxic activity both in hematologic and solid cancer cells and induced AML cell differentiation. Emetine also inhibited AML stem/progenitor cells, as evidenced by decreased expression of CD34, CD97, CD99, and CD123 in KG-1a cells, indicating anti-AML stem/progenitor cell activities. The administration of emetine at a dosage of 10 mg/kg for two weeks showed no significant toxicity and significantly reduced xenograft leukemic growth in vivo. NF-κB activation was reduced in emetine-treated KG-1a cells, as shown by reduced phospho-NF-κB p65 (S529) and nuclear NF-κB p65. DNA fragmentation, YO-PRO-1 staining, mitochondrial depolarization and increased levels of active caspase-3 and cleaved PARP (Asp214) were detected in emetine-treated KG-1a cells. Moreover, treatment with the pancaspase inhibitor Z-VAD(OMe)-FMK partially prevented the apoptotic cell death induced by emetine. Emetine treatment also increased cellular and mitochondrial reactive oxygen species, and emetine-induced apoptosis in KG-1a cells was partially prevented by the antioxidant N-acetylcysteine, indicating that emetine induces apoptosis, at least in part, by inducing oxidative stress. Overall, these studies indicate that emetine is a novel potential anti-AML agent with promising activity against stem/progenitor cells, encouraging the development of further studies aimed at its clinical application.
Editor: United States: Springer Nature B.V
Idioma: Inglês

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Emetine induces oxidative stress, cell differentiation and NF-κB inhibition, suppressing AML stem/progenitor cells

Silva, Suellen L R ; Dias, Ingrid R S B ; Rodrigues, Ana Carolina B da C ; Costa, Rafaela G A ; Oliveira, Maiara de S ; Barbosa, Gabriela A da C ; Soares, Milena B P ; Dias, Rosane B ; Valverde, Ludmila F ; Rocha, Clarissa A G ; Roy, Nainita ; Park, Christopher Y ; Bezerra, Daniel P

United States: Springer Nature B.V

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