Soy isoflavones induces mitophagy to inhibit the progression of osteosarcoma by blocking the AKT/mTOR signaling pathway.
Mol Med
; 30(1): 5, 2024 Jan 08.
Article
em En
| MEDLINE
| ID: mdl-38191316
ABSTRACT
BACKGROUND:
Soy isoflavones (SI) is a natural bioactive substance exhibiting beneficial effects on human health. This study aims to elucidate the therapeutic potential of SI in the treatment of osteosarcoma (OS) and to investigate the underlying mechanisms, particularly focusing on mitophagy.METHODS:
The effects of SI on the proliferation, apoptosis, migration, and invasion of U2OS cells were analyzed. Mitophagy was assessed through multiple parameters mitochondrial autophagosomes, mitochondrial membrane potential, autophagy-related proteins, reactive oxygen species (ROS), and oxygen consumption rate (OCR). Protein levels related to apoptosis, autophagy, and the AKT/mTOR pathway were analyzed using western blot. The therapeutic efficacy of SI was further identified using a mouse tumor xenograft model. Cell apoptosis and proliferation in tumor xenografts were detected by TUNEL staining and immunohistochemistry (IHC), respectively.RESULTS:
SI dose-dependently suppressed the viability, colony formation, migration, and invasion of U2OS cells, and enhanced the apoptosis. SI also dose-dependently induced mitophagy in OS cells, evidenced by an increase in autophagosomes and ROS levels, a decrease in mitochondrial membrane potential and OCR, and concomitant changes in autophagy-related proteins. Mdivi-1, an inhibitor of mitophagy, reversed the anti-tumor effects of SI on U2OS cells. In addition, SI blocked the AKT/mTOR pathway in U2OS cells. SC-79, an AKT agonist, reversed the effect of SI on inducing mitophagy. Moreover, SI also promoted cell apoptosis and mitophagy in tumor xenografts in vivo.CONCLUSIONS:
SI induces mitophagy in OS cells by blocking the AKT/mTOR pathway, contributing to the inhibition of OS.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ósseas
/
Osteossarcoma
/
Isoflavonas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Med
/
Mol. med. (Camb.)
/
Molecular medicine (Cambridge)
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China