title: CC5 and CC8, two homologous disintegrins from Cerastes cerastes venom, inhibit in vitro and ex vivo angiogenesis.
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 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.
authors: Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, Institut Pasteur de Tunis, 13, Place Pasteur, 1002 Tunis, Tunisia; Université de Tunis el Manar, 1068 Tunis, Tunisia. Electronic address: benmabroukhazem@yahoo.fr.
authors: Hazem
authors: H
authors: Ben-Mabrouk
authors: Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, Institut Pasteur de Tunis, 13, Place Pasteur, 1002 Tunis, Tunisia; Université de Tunis el Manar, 1068 Tunis, Tunisia.
authors: Raoudha
authors: R
authors: Zouari-Kessentini
authors: Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, Institut Pasteur de Tunis, 13, Place Pasteur, 1002 Tunis, Tunisia; Université de Tunis el Manar, 1068 Tunis, Tunisia; INSERM, U 968, Paris F-75012, France; CNRS, UMR 7210, Paris F-75012, France; Institut de la Vision, UPMC Univ Paris 06,UMR_S 968, Paris, France.
authors: Fadoua
authors: F
authors: Montassar
authors: Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, Institut Pasteur de Tunis, 13, Place Pasteur, 1002 Tunis, Tunisia; Université de Tunis el Manar, 1068 Tunis, Tunisia.
authors: Zeineb Abdelkefi-
authors: ZA
authors: Koubaa
authors: Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, Institut Pasteur de Tunis, 13, Place Pasteur, 1002 Tunis, Tunisia; Université de Tunis el Manar, 1068 Tunis, Tunisia.
authors: Erij
authors: E
authors: Messaadi
authors: INSERM, U 968, Paris F-75012, France; CNRS, UMR 7210, Paris F-75012, France; Institut de la Vision, UPMC Univ Paris 06,UMR_S 968, Paris, France.
authors: Xavier
authors: X
authors: Guillonneau
authors: Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, Institut Pasteur de Tunis, 13, Place Pasteur, 1002 Tunis, Tunisia; Université de Tunis el Manar, 1068 Tunis, Tunisia.
authors: Mohamed
authors: M
authors: ElAyeb
authors: Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, Institut Pasteur de Tunis, 13, Place Pasteur, 1002 Tunis, Tunisia; Université de Tunis el Manar, 1068 Tunis, Tunisia.
authors: Najet
authors: N
authors: Srairi-Abid
authors: Faculté de Pharmacie, INSERM UMR 911, CRO2, Aix-Marseille Université, Marseille, France.
authors: José
authors: J
authors: Luis
authors: INSERM, UMR866, Dijon, F-21079 France; UFR Science de Santé, Univ. Bourgogne, Dijon F-21079 France.
authors: Olivier
authors: O
authors: Micheau
authors: Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, Institut Pasteur de Tunis, 13, Place Pasteur, 1002 Tunis, Tunisia; Université de Tunis el Manar, 1068 Tunis, Tunisia; Faculté de Médecine de Tunis, Tunis, Tunisia.
authors: Naziha
authors: N
authors: Marrakchi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D019483:Disintegrins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014757:Viper Venoms / Q000737:chemistry*; D017819:Viperidae
chemical_list: D020533:Angiogenesis Inhibitors; D019483:Disintegrins; D014757:Viper Venoms
keywords: Angiogenesis; Anoïkis; Disintegrins