Inhibition of lung tumor colonization and cell migration with the disintegrin crotatroxin 2 isolated from the venom of Crotalus atrox

Toxicon. 2008 Jun 1;51(7):1186-96. doi: 10.1016/j.toxicon.2008.02.004. Epub 2008 Feb 19.

Abstract

Disintegrins are low molecular weight proteins (4-15 kDa) with an RGD binding region at their binding loop. Disintegrin and disintegrin-like proteins are found in the venom of four families of snakes: Atractaspididae, Elapidae, Viperidae, and Colubridae. This report describes the biological activity of a disintegrin, crotatroxin 2, isolated by a three-step chromatography procedure from the venom of the Western diamondback rattlesnake (Crotalus atrox). The intact molecular mass for crotatroxin 2 was 7.384 kDa and 71 amino acids. Crotatroxin 2 inhibited human whole blood platelet aggregation with an IC(50) of 17.5 nM, inhibited cell (66.3p) migration by 63%, and inhibited experimental lung tumor colonization in BALB/c mice at 1000 microg/kg. Our data suggest that while crotatroxin 2 inhibits platelet aggregation, cancer cell migration, and lung tumor colonization, it is done via different integrins.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects*
  • Chromatography
  • Crotalid Venoms / isolation & purification
  • Crotalid Venoms / pharmacology*
  • Crotalus*
  • Disintegrins / isolation & purification
  • Disintegrins / pharmacology*
  • Dose-Response Relationship, Drug
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Peptide Mapping
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / isolation & purification
  • Platelet Aggregation Inhibitors / pharmacology*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tumor Cells, Cultured

Substances

  • Crotalid Venoms
  • Disintegrins
  • Platelet Aggregation Inhibitors