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Anti-Angiogenic Activity of Contortrostatin, a Disintegrin from Agkistrodon Contortrix Contortrix Snake Venom

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Abstract

Previous work in our laboratory has shown that contortrostatin (CN), a disintegrin from southern copperhead snake venom, possess anti-angiogenic activity. In the present study we further examined the anti-angiogenic activity of CN, focusing on the mechanisms of CN inhibition of angiogenesis. CN inhibited migration and invasion, and significantly altered Matrigel-induced tube formation of human umbilical vein endothelial cells (HUVEC), but did not affect cell viability, or MMP-2 and MMP-9 activity. Immunocytochemistry of HUVEC revealed that CN disrupted actin cytoskeleton and altered VE-cadherin distribution at cell–cell contacts. CN downregulated focal adhesion kinase (FAK) and paxillin tyrosine phosphorylation in adherent HUVEC. There was also significant inhibition of angiogenesis in vivo by CN as assessed by implanting Matrigel plugs in C57 mice and measuring ingrowth of blood vessels using either factor VIII staining or hemoglobin determination. In conclusion, the present findings confirm our earlier studies and demonstrate conclusively that CN possess strong anti-angiogenic activity in vitro and in vivo.

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Authors and Affiliations

  1. Departments of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, Los Angeles, California, USA

    Vladislav Golubkov & Francis S. Markland

  2. Pathology, University of Southern California, Keck School of Medicine, Los Angeles, California, USA

    Debra Hawes

  3. Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, California, USA

    Vladislav Golubkov, Debra Hawes & Francis S. Markland

Authors
  1. Vladislav Golubkov
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  2. Debra Hawes
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  3. Francis S. Markland
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Correspondence to Francis S. Markland.

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Golubkov, V., Hawes, D. & Markland, F.S. Anti-Angiogenic Activity of Contortrostatin, a Disintegrin from Agkistrodon Contortrix Contortrix Snake Venom. Angiogenesis 6, 213–224 (2003). https://doi.org/10.1023/B:AGEN.0000021396.47009.b0

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  • DOI: https://doi.org/10.1023/B:AGEN.0000021396.47009.b0

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