title: The disintegrin tzabcanin inhibits adhesion and migration in melanoma and lung cancer cells.
abstract: Integrins play an essential role in cancer survival and invasion, and they have been major targets in drug development and design. Disintegrins are small (4-16kDa) viperid snake venom proteins that exhibit a canonical integrin-binding site (often RGD). These non-enzymatic proteins inhibit integrin-mediated cell-cell and cell-extracellular matrix interactions, making them potential candidates as therapeutics in cancer and numerous other human disorders. The present study examined the cytotoxic, anti-adhesion, and anti-migration effects of a recently characterized disintegrin, tzabcanin, towards melanoma (A-375) and lung (A-549) cancer cell lines. Tzabcanin inhibits adhesion of both cells lines to vitronectin and exhibited very weak cytotoxicity towards A-375 cells; however, it had no effect on cell viability of A-549 cells. Further, tzabcanin significantly inhibited migration of both cell lines in cell scratch/wound healing assays. Flow cytometric analysis indicates that both A-375 and A-549 cell lines express integrin αvβ3, a critical integrin in tumor motility and invasion, and a major receptor of the extracellular matrix protein vitronectin. Flow cytometric analysis also identified αvβ3 as a binding site of tzabcanin. These results suggest that tzabcanin may have utility in the development of anticancer therapies, or may be used as a biomarker to detect neoplasms that over-express integrin αvβ3.
authors.affiliation: School of Biological Sciences, University of Northern Colorado, 501 20th St., CB 92, Greeley, CO 80639-0017, USA; Current address, Department of Pharmacology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065-4805, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Saviola
authors.affiliation: School of Biological Sciences, University of Northern Colorado, 501 20th St., CB 92, Greeley, CO 80639-0017, USA.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Burns
authors.affiliation: School of Biological Sciences, University of Northern Colorado, 501 20th St., CB 92, Greeley, CO 80639-0017, USA; Microbial Biotechnology and Protein Research Laboratory, Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Assam, India.
authors.forename: Ashis K
authors.initials: AK
authors.lastname: Mukherjee
authors.affiliation: School of Biological Sciences, University of Northern Colorado, 501 20th St., CB 92, Greeley, CO 80639-0017, USA. Electronic address: stephen.mackessy@unco.edu.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Mackessy
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019483:Disintegrins / Q000008:administration & dosage*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D019483:Disintegrins; D039302:Integrin alphaVbeta3; C000614734:tzabcanin protein, Crotalus simus tzabcan
keywords: Cell adhesion; Crotalus simus tzabcan; Extracellular matrix; Flow cytometry; Integrins; Metastasis; Toxin drugs; Vitronectin