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.
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.
Sánchez
Elda E
EE
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.sanchez@tamuk.edu
Rodríguez-Acosta
Alexis
A
Palomar
Rene
R
Lucena
Sara E
SE
Bashir
Sajid
S
Soto
Julio G
JG
Pérez
John C
JC
D000595:Amino Acid Sequence; D000818:Animals; D017837:Bothrops; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D017124:Conserved Sequence; D003435:Crotalid Venoms / Q000737:chemistry / Q000494:pharmacology*; D019483:Disintegrins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects; D008545:Melanoma / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D012878:Skin Neoplasms / Q000378:metabolism; D012910:Snake Venoms / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013020:South America
D003435:Crotalid Venoms; D019483:Disintegrins; D005353:Fibronectins; D010975:Platelet Aggregation Inhibitors; D012910:Snake Venoms; C540905:colombistatin, Bothrops colombiensis