Agkistin-s, a disintegrin domain, inhibits angiogenesis and induces BAECs apoptosis

Previous work in our laboratory has shown agkistin, a snake venom metalloproteases (SVMPs) from the venom of Agkistrodon halys, possesses antiplatelet aggregation activity. In this study, we further examined the antiangiogenic activity of agkistin‐s, the disintegrin domain of agkistin. Recombinant agkistin‐s was produced in Escherichia coli by subcloning its cDNA into pET28a vector, and the effect of purified agkistin‐s was evaluated. At the concentration of 0.5–1.5 µM, the recombinant agkistin‐s exhibited inhibitory activities on the bovine aortic endothelial cells (BAECs) migration and proliferation in a dose‐dependent manner. In addition, it exhibited an effective antiangiogenic effect when assayed by using the 10‐day‐old embryo chick CAM model and effectively inhibits the tube‐like structure formation. Furthermore, it potently induced BAECs apoptosis as examined by flow cytometric assays. J. Cell. Biochem. 99: 1517–1523, 2006. © 2006 Wiley‐Liss, Inc.