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Article

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

1
Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil
2
Global Vet Pathology, Montgomery Village, MD 20886, USA
3
Aging Institute and Division of Infectious Diseases, Department of Medicine, University of Pittsburg, Pittsburgh, PA 15261, USA
4
Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
5
Proteases & Tissue Remodeling Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
Received: 25 June 2020 / Revised: 12 September 2020 / Accepted: 14 September 2020 / Published: 24 September 2020
(This article belongs to the Section Bacterial Toxins)
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. View Full-Text
Keywords: toxin; canine osteosarcoma; Bacillus anthracis; anthrax; apoptosis toxin; canine osteosarcoma; Bacillus anthracis; anthrax; apoptosis
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MDPI and ACS Style

Mackowiak da Fonseca, J.; Mackowiak da Fonseca, I.I.; Nagamine, M.K.; Massoco, C.d.O.; Nishiya, A.T.; Ward, J.M.; Liu, S.; Leppla, S.H.; Bugge, T.H.; Dagli, M.L.Z. Inhibitory Effects of a Reengineered Anthrax Toxin on Canine and Human Osteosarcoma Cells. Toxins 2020, 12, 614. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12100614

AMA Style

Mackowiak da Fonseca J, Mackowiak da Fonseca II, Nagamine MK, Massoco CdO, Nishiya AT, Ward JM, Liu S, Leppla SH, Bugge TH, Dagli MLZ. Inhibitory Effects of a Reengineered Anthrax Toxin on Canine and Human Osteosarcoma Cells. Toxins. 2020; 12(10):614. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12100614

Chicago/Turabian Style

Mackowiak da Fonseca, Jonathan, Ivone I. Mackowiak da Fonseca, Marcia K. Nagamine, Cristina d.O. Massoco, Adriana T. Nishiya, Jerrold M. Ward, Shihui Liu, Stephen H. Leppla, Thomas H. Bugge, and Maria L.Z. Dagli 2020. "Inhibitory Effects of a Reengineered Anthrax Toxin on Canine and Human Osteosarcoma Cells" Toxins 12, no. 10: 614. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12100614

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