Anti-angiogenic activities of two recombinant disintegrins derived from the Mohave and Prairie rattlesnakes

Angiogenesis plays a crucial role in the growth and spread of cancer. New vascularization nourishes cancer cells with oxygen and nutrients, allowing these cells to grow, invade nearby tissue, spread to other parts of the body, and form new colonies of cancer cells. Tumor angiogenesis consists of endothelial cell proliferation, migration, and tube formation into the tumor mass. The study of natural and synthetic angiogenesis inhibitors is a promising area for therapeutics since tumors cannot grow or spread without the formation of new blood vessels. Anti-angiogenic activities have been identified in peptides known as disintegrins. Disintegrins are a family of small proteins (45-84 amino acids in length), many which are found in snake venom that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. This study reports two recombinant disintegrins (r-mojastin 1 and r-viridistatin 2) inhibiting, with similar effectiveness, distinct steps in angiogenesis such as proliferation, adhesion to fibronectin, migration, and tube formation in vitro and in vivo. Both recombinant disintegrins bind to αvβ3 and αvβ5 receptors that are upregulated in tumor endothelial cells, having a higher binding activity to αvβ3 integrin.