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Effect of the disintegrin eristostatin on melanoma-natural killer cell interactions.

Abstract
Malignant melanoma is difficult to treat due to its resistance to chemotherapeutic regimens. Discovery of new pharmaceuticals with inhibitory potential can be helpful in the development of novel treatments. The snake venom disintegrin eristostatin, from the viper Eristicophis macmahoni, caused immunodeficient mice to be significantly protected from development of lung colonization when melanoma cells and the disintegrin were co-injected in vivo into the lateral tail vein compared to vehicle controls. Cytotoxicity assays suggested that eristostatin makes the melanoma cells a better target for lysis by human natural killer cells. Direct binding assays using atomic force microscopy showed eristostatin does specifically bind the surface of the six melanoma cell lines tested. Eristostatin binding was partially inhibited by the addition of soluble RGDS peptide, suggesting an integrin as one likely, but not the sole, binding partner. Studies done with melanoma cells on a culture dish and natural killer cells attached to a cantilever tip in atomic force microscopy showed four major populations of interactions which exhibited altered frequency and unbinding strength in the presence of eristostatin.
AuthorsStefan Hailey, Elizabeth Adams, Ryan Penn, Alice Wong, Mary Ann McLane
JournalToxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 61 Pg. 83-93 (Jan 2013) ISSN: 1879-3150 [Electronic] England
PMID23147645 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2012 Elsevier Ltd. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Fluorescent Dyes
  • Peptides
  • Platelet Aggregation Inhibitors
  • Recombinant Proteins
  • Viper Venoms
  • eristostatin
  • Fluorescein-5-isothiocyanate
Topics
  • Antineoplastic Agents
  • Cell Line, Tumor
  • Cell Separation
  • Flow Cytometry
  • Fluorescein-5-isothiocyanate
  • Fluorescent Dyes
  • Humans
  • Killer Cells, Natural (drug effects)
  • Melanoma (drug therapy)
  • Microscopy, Atomic Force
  • Microscopy, Confocal
  • Peptides (pharmacology)
  • Platelet Aggregation (drug effects)
  • Platelet Aggregation Inhibitors (pharmacology)
  • Recombinant Proteins (pharmacology)
  • Viper Venoms (pharmacology)

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