4-O-methylascochlorin-stimulated HIF-1α expression induces the epithelial mesenchymal transition and cell survival in breast cancer cells.
Toxicol In Vitro
; 81: 105342, 2022 Jun.
Article
em En
| MEDLINE
| ID: mdl-35248696
ABSTRACT
4-O-Methyl-ascochlorin (MAC), a derivative of the prenyl-phenol antibiotic ascochlorin, promotes accumulation of HIF-1α. In this study, we investigated the molecular mechanisms of the effect of MAC on cell migration and mesenchymal epithelial transition (EMT) processes in breast cancer cells. MAC upregulated cell motility and migration regardless of cell viability, and promoted EMT features by regulating EMT-related proteins and transcription. In addition, the MAC-induced increase in the EMT was closely related to activation of HIF-1α expression. However, the MAC-induced EMT was not associated with AMPK phosphorylation or intracellular ROS, which stimulate HIF-1α expression. Similarly, HIF-1α-mediated autophagy induced by MAC was not related to EMT-related proteins. Inhibition of HIF-1α activity inhibited MAC-stimulated cell migration and increased MAC-induced cell death, indicating that HIF-1α activation is important for MAC-mediated cell migration and survival in breast cancer cells. Together, these results suggest that MAC can be used to investigate the link between HIF-1α activation and other oncogenes or tumor suppressors in breast cancer cells.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Transição Epitelial-Mesenquimal
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article