Inhibitory Effects of a Reengineered Anthrax Toxin on Canine and Human Osteosarcoma Cells

Autor(es)

da Fonseca, Jonathan Mackowiak ^[1] ; Mackowiak da Fonseca, Ivone Izabel ^[1] ; Nagamine, Marcia Kazumi ^[1] ; Massoco, Cristina de Oliveira ^[1] ; Nishiya, Adriana Tomoko ^[1] ; Ward, Jerrold Michael ^[2] ; Liu, Shihui ^{[3, 4]} ; Leppla, Stephen Howard ^[5] ; Bugge, Thomas Henrik ^[6] ; Zaidan Dagli, Maria Lucia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, BR-05508270 Sao Paulo, SP - Brazil

^[2] Global Vet Pathol, Montgomery Village, MD 20886 - USA

^[3] Univ Pittsburg, Div Infect Dis, Dept Med, Pittsburgh, PA 15261 - USA

^[4] Univ Pittsburg, Aging Inst, Dept Med, Pittsburgh, PA 15261 - USA

^[5] NIAID, Microbial Pathogenesis Sect, Lab Parasit Dis, NIH, Bethesda, MD 20892 - USA

^[6] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, NIH, Bethesda, MD 20892 - USA

• Tipo de documento: Artigo Científico
• Fonte: TOXINS; v. 12, n. 10 OCT 2020.
• Citações Web of Science: 0

Resumo

Canine and human osteosarcomas (OSA) share similarities. Novel therapies are necessary for these tumours. The Bacillus anthracis toxin was reengineered to target and kill cells with high expressions of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA). Since canine OSA express MMPs and uPA, we assessed whether the reengineered toxin could show efficacy against these tumours. Two OSA cell lines (canine D17 and human MG63) and a non-neoplastic canine osteoblastic cell line (COBS) were used. Cells were treated with different concentrations of the reengineered anthrax toxin and cell viability was quantified using MTT assay. The cell cycle, apoptosis, and necrosis were analysed by flow cytometry. The wound-healing assay was performed to quantify the migration capacity of treated cells. D17 and MG63 cells had significantly decreased viability after 24 h of treatment. Cell cycle analysis revealed that OSA cells underwent apoptosis when treated with the toxin, whereas COBS cells arrested in the G1 phase. The wound-healing assay showed that D17 and MG63 cells had a significantly reduced migration capacity after treatment. These results point for the first time towards the in vitro inhibitory effects of the reengineered anthrax toxin on OSA cells; this reengineered toxin could be further tested as a new therapy for OSA. (AU)

• Processo FAPESP: 16/20479-7 - Avaliação dos efeitos da toxina do Bacillus anthracis reengenheirada, ativada pela uroquinase (uPA) e metaloproteinases (MMPs), em Hemangiossarcoma canino: estudos in vitro e in vivo
• Beneficiário: Márcia Kazumi Nagamine
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/12855-1 - Investigação da atividade do peptídeo Q-conexina carboxil-terminal (ACT1) associado ao inibidor de histonas desacetilases butirato sódico e a antineoplásicos convencionais, para o tratamento de tumores mamários caninos: ensaios in vitro.
• Beneficiário: Ivone Izabel Mackowiak da Fonseca
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/16776-3 - Avaliação dos efeitos da toxina do Bacillus anthracis reengenheirada, ativada pela urokinase (UPA) e metaloproteinases (MMPs), para o tratamento de melanomas e de outras neoplasias de cães.
• Beneficiário: Maria Lucia Zaidan Dagli
• Modalidade de apoio: Auxílio à Pesquisa - Regular