Regulation of valproic acid induced EMT by AKT/GSK3ß/ß-catenin signaling pathway in triple negative breast cancer.
Mol Biol Rep
; 48(2): 1335-1343, 2021 Feb.
Article
em En
| MEDLINE
| ID: mdl-33515347
ABSTRACT
Valproic acid (VPA) is a selective histone deacetylation (HDAC) inhibitor and exerts anti-cancer properties in different types of cancer. The epithelial-to-mesenchymal transition (EMT) mediating by different signaling cascade can be a potential target in aggressive human cancers. Therefore, we aimed to clarified the unravel relationship between AKT/GSK3ß/ß-catenin signalling pathway and VPA-induced EMT in triple negative breast cancer (TNBC). The cytotoxicity of VPA in MDA-MB-231 TNBC and MCF-10A control cells was evaluated. Alterations in the expression levels of Snail, E-cadherin, AKT, GSK3ß, ß-catenin were analyzed by RT-PCR. Additionally, Annexin V, cell cycle and wound healing assays were performed. Our results showed that VPA remarkably inhibited the growth of TNBC cell and triggered apoptotic cell death through G0/G1 arrest. Furthermore, VPA increased cell migration and activated the EMT process through significantly increasing Snail expression and in turn downregulation of E-cadherin and GKS3ß levels. However, the level of AKT and ß-catenin was reduced after treatment of VPA. Our data showed that VPA induced EMT process and cell migration in TNBC cells. However, AKT/GSK3ß/ß-catenin signaling pathway did not mediate EMT activation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Valproico
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Proteínas Proto-Oncogênicas c-akt
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Beta Catenina
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Neoplasias de Mama Triplo Negativas
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Glicogênio Sintase Quinase 3 beta
Limite:
Female
/
Humans
Idioma:
En
Revista:
Mol Biol Rep
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Turquia