CC5 and CC8, two homologous disintegrins from Cerastes cerastes venom, inhibit in vitro and ex vivo angiogenesis

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• 作者：Hazem Ben-Mabrouk^a ; ^b ; ^{benmabroukhazem@yahoo.fr" class="auth_mail" title="E-mail the corresponding author} ; Raoudha Zouari-Kessentini^a ; ^b ; Fadoua Montassar^a ; ^b ; ^c ; ^d ; ^e ; Zeineb Abdelkefi- Koubaa^a ; ^b ; Erij Messaadi^a ; ^b ; Xavier Guillonneau^c ; ^d ; ^e ; Mohamed ElAyeb^a ; ^b ; Najet Srairi-Abid^a ; ^b ; José ; Luis^f ; Olivier Micheau^g ; ^h ; Naziha Marrakchi^a ; ^b ; ⁱ
• 关键词：Disintegrins ; Angiogenesis ; Anoï ; kis
• 刊名：International Journal of Biological Macromolecules
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：86
• 期：Complete
• 页码：670-680
• 全文大小：3008 K

文摘

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 αvβ3 and α5β1 binding. The use of CC5 and/or CC8 could provide a beneficial tool to inhibit abnormal angiogenesis and to induce cancer regression.