PIVL, a snake venom Kunitz-type serine protease inhibitor, inhibits in vitro and in vivo angiogenesis.

Abstract

Development and homeostasis of the vascular system requires integrin-promoting endothelial cell adhesion, migration and survival. Nowadays, integrins represent potential targets for pharmacological agents and open new avenues for the control of metastatic spread in the treatment of tumor malignancies. We have already reported that PIVL, a serine protease inhibitor isolated from Macrovipera lebetina venom, displays an anti-tumor effect through interference with integrin receptor function. Here, we report that PIVL inhibits human vascular endothelial cell adhesion and migration onto fibrinogen and fibronectin in a dose-dependent manner without any cytotoxicity. Furthermore, we show that PIVL increases microtubule dynamic instability in HMEC-1 transfected with EGFP-tagged α-tubulin. Using Matrigel™ and chick chorioallantoic membrane assays, we demonstrate that PIVL exhibits a strong anti-angiogenic effect both in vitro and in vivo. Interestingly, results herein reveal that the potent anti-angiogenic properties of PIVL are mediated by its RGD-like motif ((41)RGN(43)).

• Authors: Maram Morjen, Stéphane Honoré, Amine Bazaa, Zaineb Abdelkafi-Koubaa, Ameneallah Ellafi, Kamel Mabrouk, Hervé Kovacic, Mohamed El Ayeb, Naziha Marrakchi, José Luis
• Journal: Microvascular research (Microvasc Res) Vol. 95 Pg. 149-56 (Sep 2014) ISSN: 1095-9319 [Electronic] United States
• PMID: 25173589 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Integrin alpha5beta1
• Integrin alphaVbeta3
• PIVL, Macrovipera lebetina
• Serine Proteinase Inhibitors
• Viper Venoms

Topics

• Amino Acid Motifs
• Angiogenesis Inhibitors (chemistry, isolation & purification, pharmacology)
• Animals
• Cell Adhesion (drug effects)
• Cell Line
• Cell Movement (drug effects)
• Chick Embryo
• Chorioallantoic Membrane (blood supply)
• Dose-Response Relationship, Drug
• Endothelial Cells (drug effects, enzymology)
• Humans
• Integrin alpha5beta1 (antagonists & inhibitors, metabolism)
• Integrin alphaVbeta3 (antagonists & inhibitors, metabolism)
• Microtubules (drug effects, metabolism)
• Neovascularization, Physiologic (drug effects)
• Serine Proteinase Inhibitors (chemistry, isolation & purification, pharmacology)
• Time Factors
• Transfection
• Viper Venoms (chemistry)