The STAT-ROS cycle extends IFNinduced cancer cell apoptosis.
Int J Oncol
; 52(1): 305-313, 2018 Jan.
Article
em En
| MEDLINE
| ID: mdl-29115415
ABSTRACT
In mammals, the signal transducer and activator of transcription (STAT) protein processes mitochondria importation targets and mitochondria respiratory complexes, and triggers reactive oxygen species (ROS) generation, which conversely rapidly initiates the activation of STAT. Interferon (IFN) administration increases cancer cell apoptosis via STAT activation and ROS accumulation. However, the existence of a STAT-ROS cycle and how it affects IFNinduced cancer cellular apoptosis are unclear. In the present study, we used MCF7 breast cancer cells and confirmed that a combination of IFNα/ß/γ incubation induced STAT1/3 phosphorylation and mitochondria importation, which increased mitochondria respiratory complexes, the cellular oxygen consumption rate (OCR), and ROS production, followed by cellular apoptosis. We also found that STAT1/3 overexpression induced mitochondria respiratory complexes and ROS production. Additionally, ROS induced by H2O2 induced phosphorylation of STAT1/3 and promoted mitochondria importation. STAT1/3 deletion suppressed H2O2-induced acute cellular OCR, increasing the ROS level and indicating that STAT1/3 is necessary for ROS-induced mitochondria OCR and further ROS production, suggesting the existence of a STAT-ROS cycle. We next found that IFN induced mitochondria respiratory complexes followed by induction of OCR, ROS, and apoptosis, which were partially blocked by STAT1/3 deletion. Additionally, the suppression of ROS inhibited IFNinduced STAT1/3 activation. Finally, we discovered that this cycle exists also in A431 and HeLa cancer cells. These results indicate that a STAT-ROS cycle extends IFNinduced cellular apoptosis.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Saude_da_mulher
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Colo_do_utero
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Tipos_de_cancer
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Colo_do_utero
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Interferons
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Espécies Reativas de Oxigênio
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Fatores de Transcrição STAT
Limite:
Female
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Humans
Idioma:
En
Revista:
Int J Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article