Regulation of ROS-Dependent JNK Pathway by 2’-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells
The present study demonstrated that 2′-hydroxycinnamaldehyde (2′-HCA) induced apoptosis in human promyelocytic leukemia HL-60 cells through the activation of mitochondrial pathways including (1) translocation of Bim and Bax from the cytosol to mitochondria, (2) downregulation of Bcl-2 protein expres...
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| Autores principales: | , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/fe677e391a9f4ab097880eb97737028d |
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| Sumario: | The present study demonstrated that 2′-hydroxycinnamaldehyde (2′-HCA) induced apoptosis in human promyelocytic leukemia HL-60 cells through the activation of mitochondrial pathways including (1) translocation of Bim and Bax from the cytosol to mitochondria, (2) downregulation of Bcl-2 protein expression, (3) cytochrome <i>c</i> release into the cytosol, (4) loss of mitochondrial membrane potential (Δ<i>Ψ<sub>m</sub></i>), and (5) caspase activation. 2′-HCA also induced the activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase1/2 (ERK1/2) in HL-60 cells. The pharmacological and genetic inhibition of JNK effectively prevented 2′-HCA-induced apoptosis and activator protein-1 (AP-1)-DNA binding. In addition, 2′-HCA resulted in the accumulation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH) and protein thiols (PSH) in HL-60 cells. NAC treatment abrogated 2′-HCA-induced JNK phosphorylation, AP-1-DNA binding, and Bim mitochondrial translocation, suggesting that oxidative stress may be required for 2′-HCA-induced intrinsic apoptosis. Xenograft mice inoculated with HL-60 leukemia cells demonstrated that the intraperitoneal administration of 2′-HCA inhibited tumor growth by increasing of TUNEL staining, the expression levels of nitrotyrosine and pro-apoptotic proteins, but reducing of PCNA protein expression. Taken together, our findings suggest that 2′-HCA induces apoptosis via the ROS-dependent JNK pathway and could be considered as a potential therapeutic agent for leukemia. |
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