title: In vitro antitumor and antiangiogenic effects of Bothropoidin, a metalloproteinase from Bothrops pauloensis snake venom.
abstract: Breast cancer is a highly malignant carcinoma and remains the second leading cause of mortality among women. The antitumor effects of metalloproteinases and disintegrins from snake venom on various types of cancer cells have been investigated. In this study, we evaluated the antitumor and antiangiogenic effects on MDA-MB-231 human breast cancer cells and endothelial cells induced by Bothropoidin, a disintegrin-like metalloproteinase isolated from Bothrops pauloensis snake venom. At 24h after treatment at 100μg/mL, Bothropoidin exerted a moderate cytotoxic effect of 30% on MDA-MB-231 versus 10% cytotoxicity against MCF10A (a non-tumorigenic breast cell line), a significant difference that suggests a possible preference by this protein for targets in cancer cells. Early and late apoptosis of MDA-MB-231 was observed after Bothropoidin treatment (10μg/mL and 40μg/mL). Furthermore, this toxin inhibited not only the adhesion of MDA-MB-231 cells in a dose-dependent manner but also cell migration by approximately 45%. In addition, Bothropoidin decreased endothelial cells viability and adhesion in Matrigel and inhibited in vitro angiogenesis in Matrigel stimulated by bFGF, showing significantly fewer formed vessels. The results demonstrated that Bothropoidin has potent in vitro antitumor and antiangiogenic effect and represents a biotechnological tool for elucidating the antitumor effect of disintegrins-like metalloproteinases in cancer cells.
authors.affiliation: Laboratory of Biochemistry and Animal Toxins, Institute of Genetics and Biochemistry, Federal University of Uberlandia, UFU, Uberlandia, MG, Brazil.
authors.forename: Denise de Oliveira
authors.initials: DO
authors.lastname: Guimarães
authors.affiliation: Laboratory of Biochemistry and Animal Toxins, Institute of Genetics and Biochemistry, Federal University of Uberlandia, UFU, Uberlandia, MG, Brazil. Electronic address: lsdaiana@yahoo.com.br.
authors.forename: Daiana Silva
authors.initials: DS
authors.lastname: Lopes
authors.affiliation: Laboratory of Biochemistry and Animal Toxins, Institute of Genetics and Biochemistry, Federal University of Uberlandia, UFU, Uberlandia, MG, Brazil.
authors.forename: Fernanda Van Petten Vasconcelos
authors.initials: FV
authors.lastname: Azevedo
authors.affiliation: Laboratory of Biochemistry and Animal Toxins, Institute of Genetics and Biochemistry, Federal University of Uberlandia, UFU, Uberlandia, MG, Brazil.
authors.forename: Sarah Natalie Cirilo
authors.initials: SN
authors.lastname: Gimenes
authors.affiliation: Laboratory of Biochemistry and Animal Toxins, Institute of Genetics and Biochemistry, Federal University of Uberlandia, UFU, Uberlandia, MG, Brazil.
authors.forename: Makswell Almeida
authors.initials: MA
authors.lastname: Silva
authors.affiliation: Laboratory of Biochemistry and Animal Toxins, Institute of Genetics and Biochemistry, Federal University of Uberlandia, UFU, Uberlandia, MG, Brazil.
authors.forename: David Collares
authors.initials: DC
authors.lastname: Achê
authors.affiliation: Department of Chemical and Physical, State University of Southwest Bahia (UESB), 45506-210 Jequie, BA, Brazil.
authors.forename: Mário Sérgio Rocha
authors.initials: MS
authors.lastname: Gomes
authors.affiliation: Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlandia, UFU, Uberlandia, MG, Brazil.
authors.forename: Lara
authors.initials: L
authors.lastname: Vecchi
authors.affiliation: Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlandia, UFU, Uberlandia, MG, Brazil.
authors.forename: Luiz Ricardo
authors.initials: LR
authors.lastname: Goulart
authors.affiliation: Laboratory of Biochemistry and Animal Toxins, Institute of Genetics and Biochemistry, Federal University of Uberlandia, UFU, Uberlandia, MG, Brazil.
authors.forename: Kelly Aparecida Geraldo
authors.initials: KA
authors.lastname: Yoneyama
authors.affiliation: Laboratory of Biochemistry and Animal Toxins, Institute of Genetics and Biochemistry, Federal University of Uberlandia, UFU, Uberlandia, MG, Brazil.
authors.forename: Renata Santos
authors.initials: RS
authors.lastname: Rodrigues
authors.affiliation: Laboratory of Biochemistry and Animal Toxins, Institute of Genetics and Biochemistry, Federal University of Uberlandia, UFU, Uberlandia, MG, Brazil. Electronic address: veridiana@ufu.br.
authors.forename: Veridiana de Melo
authors.initials: VM
authors.lastname: Rodrigues
mesh_terms: D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017837:Bothrops; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003435:Crotalid Venoms / Q000201:enzymology*; D006801:Humans; D045726:Metalloproteases / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003435:Crotalid Venoms; D045726:Metalloproteases
keywords: Antiangiogenic; Antitumor; MDA-MB-231 cells; Snake venom metalloproteinase