CC5 and CC8, two homologous disintegrins from Cerastes cerastes venom, inhibit in vitro and ex vivo angiogenesis.
Int J Biol Macromol
; 86: 670-80, 2016 May.
Article
en En
| MEDLINE
| ID: mdl-26853827
ABSTRACT
Angiogenesis constitutes a fundamental step in tumor progression. Thus, targeting tumour angiogenesis has been identified to be promising in cancer treatment. In this work, CC5 and CC8, two highly homologous disintegrins isolated from the venom Cerastes cerastes viper from the south of Tunisia, were assessed for their anti-angiogenic effect by testing their ability to interfere with viability, adhesion, migration and angiogenesis of Human Microvascular Endothelial Cells, HMEC-1 and HBMEC. We found that CC5 and CC8 displayed pro-apoptotic potential in HMEC-1 cells. Anoïkis like induced by these two disintegrins was evidenced by cell detachment, down regulation of FAK/AKT/PI3K axis and caspase activation. In addition, both CC5 and CC8 exhibited in vitro anti-adhesive, anti-migratory and anti-proliferative effects on endothelial cells HBMEC. These effects appeared to require RGD and/or WGD loops disintegrin. CC5 and CC8 also inhibited tube-formation on matrigel and displayed potent anti-angiogenic activities as assessed ex vivo, using both the embryo chick chorioallantoic membrane model (CAM) and rat aortic ring assay. Altogether our results demonstrate that CC5 and CC8, are potent inhibitors of angiogenesis, by disrupting αvß3 and α5ß1 binding. The use of CC5 and/or CC8 could provide a beneficial tool to inhibit abnormal angiogenesis and to induce cancer regression.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Venenos de Víboras
/
Homología de Secuencia de Aminoácido
/
Neovascularización Fisiológica
/
Desintegrinas
/
Inhibidores de la Angiogénesis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Biol Macromol
Año:
2016
Tipo del documento:
Article