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 microM, 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. (c) 2006 Wiley-Liss, Inc.