Contortrostatin, a snake venom disintegrin with anti-angiogenic and anti-tumor activity

Pathophysiol Haemost Thromb. 2005;34(4-5):169-76. doi: 10.1159/000092418.

Abstract

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 alphavbeta3, alphavbeta5, and/or alpha5beta1. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Disintegrins / administration & dosage
  • Disintegrins / pharmacology*
  • Disintegrins / therapeutic use
  • Female
  • Humans
  • Liposomes / administration & dosage
  • Liposomes / therapeutic use
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology
  • Snake Venoms / chemistry*
  • Transplantation, Heterologous
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Disintegrins
  • Liposomes
  • Snake Venoms
  • contortrostatin