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Colombistatin: a disintegrin isolated from the venom of the South American snake (Bothrops colombiensis) that effectively inhibits platelet aggregation and SK-Mel-28 cell adhesion

  • Organ Toxicity and Mechanisms
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Abstract

Snake venoms are complex mixtures of proteins, which affect the vital biologic systems of prey, as well as humans. Envenomation leads to immobilization by paralysis, cardiac, and circulatory failure. These same venom proteins that cause havoc in the physiologic system could be used as therapeutic agents. Disintegrins and disintegrin-like proteins are molecules found in the venom of four snake families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The disintegrins are non-enzymatic proteins that inhibit cell–cell interactions, cell–matrix interactions, and signal transduction. These proteins may have potential in the treatment of strokes, heart attacks, cancers, osteoporosis, and diabetes. The present study describes the isolation and characterization of a disintegrin (colombistatin) found in the venom of the Venezuelan snake mapanare (Bothrops colombiensis). Colombistatin was purified by a two-step high-performance liquid chromatography procedure, which included reverse phase C18 and size exclusion protein Pak 60. Colombistatin inhibited ADP-induced platelet aggregation, human urinary (T24) and skin melanoma (SK-Mel-28) cancer cell adhesion to fibronectin, and cell migration. Colombistatin contained 72 amino acids with a mass of 7.778 kDa as determined by mass spectrometry. Colombistatin could be used as a therapeutic tool in the treatment of melanoma cancers and also thrombotic diseases.

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Acknowledgments

This research was supported by grants to the NTRC at Texas A&M University-Kingsville: NIH/NCRR #1 P40 RR018300-01, NIH/RIMI #5 PMD000216-02, and NIH/SCORE #5 S06 GM008107-29; grants to San Jose State University: NIH/SCORE 2S06GM008192; and grants from the Universidad Central de Venezuela: FONACIT (G-2005000400). We thank Luis Fernando Navarrete for venom extractions done at the Instituto de Medicina Tropical, Universidad Central de Venezuela. We also thank Nora Diaz DeLeon for her technical assistance.

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Authors and Affiliations

  1. Natural Toxins Research Center, College of Arts and Science, Texas A&M University-Kingsville, 975 W. Avenue B. MSC 158, Kingsville, TX, 78363, USA

    Elda E. Sánchez, Rene Palomar, Sara E. Lucena & John C. Pérez

  2. Instituto de Medicina Tropical, Universidad Central de Venezuela, Apartado 47423, Caracas, 1041, Venezuela

    Elda E. Sánchez & Alexis Rodríguez-Acosta

  3. Laboratory for Mass Spectrometry, Department of Chemistry, Texas A&M University-Kingsville, 920 W. Santa Gertrudis Avenue, Kingsville, TX, 78363, USA

    Sajid Bashir

  4. Biological Sciences Department, San José State University, One Washington Square, San José, CA, 95192-0100, USA

    Julio G. Soto

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  1. Elda E. Sánchez
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  2. Alexis Rodríguez-Acosta
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Correspondence to Elda E. Sánchez.

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Sánchez, E.E., Rodríguez-Acosta, A., Palomar, R. et al. Colombistatin: a disintegrin isolated from the venom of the South American snake (Bothrops colombiensis) that effectively inhibits platelet aggregation and SK-Mel-28 cell adhesion. Arch Toxicol 83, 271–279 (2009). https://doi.org/10.1007/s00204-008-0358-y

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