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Targeting α1 inserted domain (I) of α1β1 integrin by Lebetin 2 from M. lebetina transmediterranea venom decreased tumorigenesis and angiogenesis.
- Source :
-
International journal of biological macromolecules [Int J Biol Macromol] 2018 Oct 01; Vol. 117, pp. 790-799. Date of Electronic Publication: 2018 Jun 02. - Publication Year :
- 2018
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Abstract
- Through the recent development of knowledge in biotechnology and bioinformatics, snake venoms are widely used to develop new drugs to treat diseases such as hypertension and cancer. We have previously reported that Lebetin 2 isolated from Macrovipera lebetina transmediterranea venom displays a potent anti-platelet activity and exerts a cardioprotective effect in ischemia-reperfusion (IR) injury model. Here, we report that Lebetin 2 possess an anti-tumor effect by targeting the integrin receptor function. It was thus able to inhibit both adhesion and migration of pheochromocytoma cells (PC12) and α1β1 integrin-expressing CHO cells (CHO-α1) to type I and IV collagens. Moreover, this peptide affects proliferation of PC12 cells by modulating AKT phosphorylation. Furthermore, Lebetin 2 exhibits a potent anti-angiogenic effect as assessed in vitro and ex vivo, using both the embryo chick chorioallantoic membrane model (CAM) and rat aortic ring assay. Interestingly, the interaction mode of Lebetin 2 with the integrin α1β1, assessed in silico, showed that the peptide represents a steric obstruction preventing the collagen from enforcing the interactions with the integrin.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Angiogenesis Inhibitors metabolism
Angiogenesis Inhibitors pharmacology
Angiogenesis Inhibitors therapeutic use
Animals
CHO Cells
Cell Adhesion drug effects
Cell Movement drug effects
Cell Proliferation drug effects
Cricetulus
PC12 Cells
Protein Domains
Rats
Viper Venoms metabolism
Viper Venoms pharmacology
Viper Venoms therapeutic use
Carcinogenesis drug effects
Integrin alpha1beta1 chemistry
Integrin alpha1beta1 metabolism
Neovascularization, Pathologic drug therapy
Viper Venoms chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 117
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 29870815
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2018.05.230