Contortrostatin, a Snake Venom Disintegrin with Anti-Angiogenic and Anti-Tumor ActivitySwenson S.a · Costa F.a · Ernst W.b · Fujii G.b · Markland F.S.a
aUniversity of Southern California, Keck School of Medicine, and bMolecular Express, Inc., Los Angeles, Calif., USA
Francis S. Markland
University of Southern California, Keck School of Medicine
Cancer Research Laboratory #106, 1303 North Mission Road
Los Angeles, CA 90033 (USA)
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Disintegrins are soluble peptides found in snake venom. They bind to Arg-Gly-Asp (RGD)-responsive integrins with high affinity (nM range) and block integrin function. Contortrostatin (CN), the disintegrin from southern copperhead venom, is a homodimer with a molecular weight of 13,500. Each chain contains 65 amino acids with an Arg-Gly-Asp motif. CN has anti-invasive and anti-adhesive activity on tumor cells and endothelial cells in vitro, and binds to integrins αvβ3, αvβ5, and/or α5β1. In vivo studies using the human metastatic breast cancer cell line MDA-MB-435, in an orthotopic xenograft model in nude mice, revealed that CN has potent anti-tumor and anti-angiogenic activity. Recent studies have employed an intravenous liposomal delivery procedure. Liposomal delivery of CN has also been shown to provide effective in vivo anti-tumor and anti-angiogenic activity in a human ovarian cancer animal model.
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