Inhibition of STAT3-NF-κB pathway facilitates SSPH I-induced ferroptosis in HepG2 cells.
Med Oncol
; 41(7): 184, 2024 Jun 22.
Article
en En
| MEDLINE
| ID: mdl-38909132
ABSTRACT
Hepatocellular carcinoma (HCC), a highly lethal solid tumor, has shown responsiveness to ferroptosis inducers, presenting new avenues in cancer treatment. Our study focuses on the roles of STAT3 and Nf-κB in regulating ferroptosis, particularly their interaction in this process. Using HepG2 cells, we employed specific inhibitors (Stattic for STAT3 and Bay11-7082 for Nf-κB) and a ferroptosis inducer, SSPH I, to dissect their collective impact on ferroptosis. Our findings reveal that inhibiting STAT3 and Nf-κB enhances ferroptosis and cytotoxicity induced by SSPH I. This is mechanistically linked to alterations in iron metabolism-related proteins and GPX4 resulting from SSPH I action, which consequently triggers a STAT3-dependent activation of Nf-κB. The inhibition of STAT3 and Nf-κB led to increased intracellular ROS, MDA, and Fe2+, along with significant GSH depletion, thereby intensifying lipid peroxidation and iron overload in HepG2 cells. This study offers a deeper understanding of the ferroptosis mechanisms in HCC. It highlights the therapeutic potential of targeting STAT3 and Nf-κB pathways to enhance the efficacy of ferroptosis-based treatments.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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FN-kappa B
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Factor de Transcripción STAT3
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Ferroptosis
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Neoplasias Hepáticas
Límite:
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article