Erybraedin A is a potential Src inhibitor that blocks the adhesion and viability of non-small-cell lung cancer cells.
Biochem Biophys Res Commun
; 502(1): 145-151, 2018 07 07.
Article
en En
| MEDLINE
| ID: mdl-29787750
ABSTRACT
The adhesion of cancer cells to the extracellular matrix (ECM) is crucial for cell proliferation, survival, and metastasis. Thus, it is necessary to inhibit cell-ECM adhesion by blocking the activation of the associated signaling to control cancer. Here, we identify erybraedin A (EBA) as a potential Src inhibitor that blocks cell adhesion and viability in non-small-cell lung cancer (NSCLC). EBA significantly inhibited the adhesion of NSCLC cells to fibronectin. EBA also markedly inhibited the activation of Src and its downstream targets, including FAK and Akt. The interaction between integrin ß1 or integrin ß3 and Src was inhibited by EBA treatment. A docking study revealed the bindings of EBA to the ATP-binding pocket and the allosteric regulatory site of the Src kinase. Additionally, EBA markedly inhibited the viability and the colony formation of NSCLC cells and induced apoptotic cell death. These results describe novel biological properties of EBA, which can block the Src-mediated adhesion and survival of NSCLC cells, suggesting the potential of EBA as an anticancer Src inhibitor that warrants further development in advanced preclinical and clinical settings.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Adhesión Celular
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Carcinoma de Pulmón de Células no Pequeñas
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Familia-src Quinasas
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Pterocarpanos
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Inhibidores de Proteínas Quinasas
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Neoplasias Pulmonares
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Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2018
Tipo del documento:
Article