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Erybraedin A is a potential Src inhibitor that blocks the adhesion and viability of non-small-cell lung cancer cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2018 Jul 07; Vol. 502 (1), pp. 145-151. Date of Electronic Publication: 2018 May 24. - Publication Year :
- 2018
-
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 β1 or integrin β3 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.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Apoptosis drug effects
Carcinoma, Non-Small-Cell Lung metabolism
Carcinoma, Non-Small-Cell Lung pathology
Cell Line, Tumor
Cell Survival drug effects
Humans
Lung Neoplasms metabolism
Lung Neoplasms pathology
src-Family Kinases metabolism
Antineoplastic Agents pharmacology
Carcinoma, Non-Small-Cell Lung drug therapy
Cell Adhesion drug effects
Lung Neoplasms drug therapy
Protein Kinase Inhibitors pharmacology
Pterocarpans pharmacology
src-Family Kinases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 502
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 29787750
- Full Text :
- https://doi.org/10.1016/j.bbrc.2018.05.137