title: Anti-invasive and anti-adhesive activities of a recombinant disintegrin, r-viridistatin 2, derived from the Prairie rattlesnake (Crotalus viridis viridis).
abstract: Snake venom disintegrins inhibit platelet aggregation and have anti-cancer activities. In this study, we report the cloning, expression, and functional activities of a recombinant disintegrin, r-viridistatin 2 (GenBank ID: JQ071899), from the Prairie rattlesnake. r-Viridistatin 2 was tested for anti-invasive and anti-adhesive activities against six different cancer cell lines (human urinary bladder carcinoma (T24), human fibrosarcoma (HT-1080), human skin melanoma (SK-Mel-28), human colorectal adenocarcinoma (CaCo-2), human breast adenocarcinoma (MDA-MB-231) and murine skin melanoma (B16F10)). r-Viridistatin 2 shares 96% and 64% amino acid identity with two other Prairie rattlesnake medium-sized disintegrins, viridin and viridistatin, respectively. r-Viridistatin 2 was able to inhibit adhesion of T24, SK-MEL-28, HT-1080, CaCo-2 and MDA-MB-231 to various extracellular matrix proteins with different affinities. r-Viridistatin 2 decreased the ability of T24 and SK-MEL-28 cells to migrate by 62 and 96% respectively, after 24 h of incubation and the invasion of T24, SK-MEL-28, HT-1080 and MDA-MB-231 cells were inhibited by 80, 85, 65 and 64% respectively, through a reconstituted basement membrane using a modified Boyden chamber. Finally, r-viridistatin 2 effectively inhibited lung colonization of murine melanoma cells in BALB/c mice by 71%, suggesting that r-viridistatin 2 could be a potent anti-cancer agent in vivo.
authors.affiliation: National Natural Toxins Research Center-NNTRC, Texas A&M University-Kingsville, MSC 158, 975 West Avenue B, Kingsville, TX 78363, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Lucena
authors.forename: Ying
authors.initials: Y
authors.lastname: Jia
authors.forename: Julio G
authors.initials: JG
authors.lastname: Soto
authors.forename: Jessica
authors.initials: J
authors.lastname: Parral
authors.forename: Esteban
authors.initials: E
authors.lastname: Cantu
authors.forename: Jeremy
authors.initials: J
authors.lastname: Brannon
authors.forename: Kristina
authors.initials: K
authors.lastname: Lardner
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Ramos
authors.forename: Agustin I
authors.initials: AI
authors.lastname: Seoane
authors.forename: Elda E
authors.initials: EE
authors.lastname: Sánchez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D003435:Crotalid Venoms / Q000737:chemistry*; D017839:Crotalus; D017931:DNA Primers; D018076:DNA, Complementary; D019483:Disintegrins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid
chemical_list: D003435:Crotalid Venoms; D017931:DNA Primers; D018076:DNA, Complementary; D019483:Disintegrins; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins