Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Cell migration inhibition activity of a non-RGD disintegrin from Crotalus durissus collilineatus venom

Texto completo
Autor(es):
de Oliveira, Isadora Sousa [1] ; Manzini, Rafaella Varzoni [1] ; Ferreira, Isabela Gobbo [1] ; Cardoso, Iara Aime [1] ; Figueiredo Bordon, Karla de Castro [1] ; Thomazela Machado, Ana Rita [2] ; Greggi Antunes, Lusania Maria [2] ; Rosa, Jose Cesar [3, 4] ; Arantes, Eliane Candiani [1]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Prot Chem Ctr, Ribeirao Preto, SP - Brazil
[4] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Mol & Cell Biol & Pathogen Bioagents, Ribeirao Preto, SP - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Journal of Venomous Animals and Toxins including Tropical Diseases; v. 24, OCT 20 2018.
Citações Web of Science: 0
Resumo

BackgroundIn recent decades, snake venom disintegrins have received special attention due to their potential use in anticancer therapy. Disintegrins are small and cysteine-rich proteins present in snake venoms and can interact with specific integrins to inhibit their activities in cell-cell and cell-ECM interactions. These molecules, known to inhibit platelet aggregation, are also capable of interacting with certain cancer-related integrins, and may interfere in important processes involved in carcinogenesis. Therefore, disintegrin from Crotalus durissus collilineatus venom was isolated, structurally characterized and evaluated for its toxicity and ability to interfere with cell proliferation and migration in MDA-MB-231, a human breast cancer cell line.MethodsBased on previous studies, disintegrin was isolated by FPLC, through two chromatographic steps, both on reversed phase C-18 columns. The isolated disintegrin was structurally characterized by Tris-Tricine-SDS-PAGE, mass spectrometry and N-terminal sequencing. For the functional assays, MTT and wound-healing assays were performed in order to investigate cytotoxicity and effect on cell migration in vitro, respectively.ResultsDisintegrin presented a molecular mass of 7287.4Da and its amino acid sequence shared similarity with the disintegrin domain of P-II metalloproteases. Using functional assays, the disintegrin showed low cytotoxicity (15% and 17%, at 3 and 6g/mL, respectively) after 24h of incubation and in the wound-healing assay, the disintegrin (3g/mL) was able to significantly inhibit cell migration (24%, p<0.05), compared to negative control.ConclusionThus, our results demonstrate that non-RGD disintegrin from C. d. collilineatus induces low cytotoxicity and inhibits migration of human breast cancer cells. Therefore, it may be a very useful molecular tool for understanding ECM-cell interaction cancer-related mechanisms involved in an important integrin family that highlights molecular aspects of tumorigenesis. Also, non-RGD disintegrin has potential to serve as an agent in anticancer therapy or adjuvant component combined with other anticancer drugs. (AU)

Processo FAPESP: 11/23236-4 - Toxinas animais nativas e recombinantes: análise funcional, estrutural e molecular
Beneficiário:Suely Vilela
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 16/11578-1 - Estudo funcional de uma desintegrina da peçonha de Crotalus durissus collilineatus
Beneficiário:Rafaella Varzoni Manzini
Linha de fomento: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 12/14996-8 - Clonagem e expressão de toxinas animais de interesse biotecnológico
Beneficiário:Eliane Candiani Arantes Braga
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 17/03580-9 - Avaliação bioquímica, estrutural e funcional de uma fosfodiesterase da peçonha de Crotalus durissus collilineatus
Beneficiário:Isadora Sousa de Oliveira
Linha de fomento: Bolsas no Brasil - Doutorado