Berberine synergises with ferroptosis inducer sensitizing NSCLC to ferroptosis in p53-dependent SLC7A11-GPX4 pathway.
Biomed Pharmacother
; 176: 116832, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38850659
ABSTRACT
Berberine (BBR) is a compound derived from Chinese herbal medicine, known for its anticancer properties through multiple signaling pathways. However, whether BBR can inhibit tumor growth by participating in ferroptosis remains unconfirmed. In this study, we demonstrated that berberine synergistically inhibited NSCLC in combination with multiple ferroptosis inducers, and this combination synergistically down-regulated the mRNA and protein expression of SLC7A11, GPX4, and NRF2, resulting in ferroptosis accompanied by significant depletion of GSH, and aberrant accumulation of reactive oxygen species and malondialdehyde. In a lung cancer allograft model, the combination treatment exhibited enhanced anticancer effects compared to using either drug alone. Notably, p53 is critical in determining the ferroptosis sensitivity. We found that the combination treatment did not elicit a synergistic anticancer effect in cells with a p53 mutation or with exogenous expression of mutant p53. These findings provide insight into the mechanism by which combination induces ferroptosis and the regulatory role of p53 in this process. It may guide the development of new strategies for treating NSCLC, offering great medical potential for personal diagnosis and treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Berberina
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Transducción de Señal
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Proteína p53 Supresora de Tumor
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Carcinoma de Pulmón de Células no Pequeñas
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Sistema de Transporte de Aminoácidos y/
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Sinergismo Farmacológico
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Ferroptosis
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Fosfolípido Hidroperóxido Glutatión Peroxidasa
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Neoplasias Pulmonares
Límite:
Animals
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Humans
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2024
Tipo del documento:
Article