Leonel Montealegre-Sánchez*, Sarah N.C. Gimenes, Daiana S. Lopes, Samuel C. Teixeira, Luis Solano-Redondo, Veridiana de Melo Rodrigues and Eliécer Jiménez-Charris* Pages 2069 - 2078 ( 10 )
Background: Disintegrins from snake venoms bind with high specificity cell surface integrins, which are important pharmacological targets associated with cancer development and progression.Objective: In this study, we isolated a disintegrin from the Porthidium lansbergii lansbergii venom and evaluated its antitumoral effects on breast cancer cells. Methods: The isolation of the disintegrin was performed on RP-HPLC and the inhibition of platelet aggregation was evaluated on human platelet-rich plasma. The inhibition of cell adhesion was also evaluated in vitro on cultures of cell lines by the MTT method as well as the inhibition of breast cancer cell migration by the wound healing assay. The binding of the disintegrin to integrin subunits was verified by flow cytometry and confocal microscopy. Finally, inhibition of angiogenesis was assessed in vitro on HUVEC cells and the concentration of VEGF was measured in the cellular supernatants. Results: The disintegrin, named Lansbermin-I, is a low molecular weight protein (< 10 kDa) that includes an RGD on its sequence identified previously. Lansbermin-I showed potent inhibition of ADP and collagen-induced platelet aggregation on human plasma and also displayed inhibitory effects on the adhesion and migration of breast cancer MCF7 and MDA-MB 231cell lines, without affecting nontumorigenic breast MCF-10A and lung BEAS cells. Additionally, Lansbermin-I prevented MCF7 cells to adhere to fibronectin and collagen, and also inhibited in vitro angiogenesis on human endothelial HUVEC cells. Conclusion: Our results display the first report on the antitumor and anti-metastatic effects of an RGDdisintegrin isolated from a Porthidium snake venom by possibly interfering with α2 and/or β1-containing integrins. Thus, Lansbermin-I could be an attractive model to elucidate the role of disintegrins against breast cancer development.
Snake venoms, ADAM proteins, Antitumor agents, Anti-angiogenic drugs, Integrins, Cancer cells.
Grupo de Nutricion, Facultad de Salud, Universidad del Valle, Cali, Laboratorio de Bioquimica e Toxinas Animais, Instituto de Biotecnologia, Universidade Federal de Uberlandia, MG, Instituto Multidisciplinar em Saude, Campus Anisio Teixeira, Universidade Federal da Bahia, BA, Laboratorio de Bioquimica e Toxinas Animais, Instituto de Biotecnologia, Universidade Federal de Uberlandia, MG, Grupo Laboratorio de Herpetologia, Facultad de Ciencias, Universidad del Valle, Cali, Laboratorio de Bioquimica e Toxinas Animais, Instituto de Biotecnologia, Universidade Federal de Uberlandia, MG, Grupo de Nutricion, Facultad de Salud, Universidad del Valle, Cali