{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:16:48Z","timestamp":1760239008404,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2015\/16776-3"],"award-info":[{"award-number":["2015\/16776-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/toxins12100614","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T01:39:33Z","timestamp":1600997973000},"page":"614","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibitory Effects of a Reengineered Anthrax Toxin on Canine and Human Osteosarcoma Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Jonathan","family":"Mackowiak da Fonseca","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivone Izabel","family":"Mackowiak da Fonseca","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia Kazumi","family":"Nagamine","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina de Oliveira","family":"Massoco","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana Tomoko","family":"Nishiya","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerrold Michael","family":"Ward","sequence":"additional","affiliation":[{"name":"Global Vet Pathology, Montgomery Village, MD 20886, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihui","family":"Liu","sequence":"additional","affiliation":[{"name":"Aging Institute and Division of Infectious Diseases, Department of Medicine, University of Pittsburg, Pittsburgh, PA 15261, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen Howard","family":"Leppla","sequence":"additional","affiliation":[{"name":"Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas Henrik","family":"Bugge","sequence":"additional","affiliation":[{"name":"Proteases &amp; Tissue Remodeling Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7031-6711","authenticated-orcid":false,"given":"Maria Lucia Zaidan","family":"Dagli","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.tvjl.2010.08.014","article-title":"Biology, diagnosis and treatment of canine appendicular osteosarcoma: Similarities and differences with human osteosarcoma","volume":"189","author":"Morello","year":"2011","journal-title":"Vet. 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