The disintegrin tzabcanin inhibits adhesion and migration in melanoma and lung cancer cells.
Int J Biol Macromol
; 88: 457-64, 2016 Jul.
Article
em En
| MEDLINE
| ID: mdl-27060015
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 αvß3, a critical integrin in tumor motility and invasion, and a major receptor of the extracellular matrix protein vitronectin. Flow cytometric analysis also identified αvß3 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 αvß3.
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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Adesão Celular
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Desintegrinas
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Neoplasias Pulmonares
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Melanoma
Limite:
Humans
Idioma:
En
Revista:
Int J Biol Macromol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos