Targeting canine mammary neoplastic epithelial cells with a reengineered anthrax toxin: first study

Vet Res Commun. 2024 Aug;48(4):2407-2428. doi: 10.1007/s11259-024-10400-5. Epub 2024 May 28.

Abstract

Mammary tumors are the most frequent type of neoplasms in intact female dogs. New therapies that target neoplastic cells without affecting normal cells are highly sought. The Bacillus anthracis toxin has been reengineered to target tumor cells that express urokinase plasminogen activators and metalloproteinases. In previous studies carried out in our laboratory, the reengineered anthrax toxin had inhibitory effects on canine oral mucosal melanoma and canine osteosarcoma cells. In this study, five canine neoplastic epithelial cell lines (four adenocarcinomas and one adenoma) and one non-neoplastic canine mammary epithelial cell line were treated with different concentrations of reengineered anthrax toxin components. Cell viability was quantified using an MTT assay and half-maximal inhibitory concentration (IC50) values. Cell lines were considered sensitive when the IC50 was lower than 5000 ng/ml. One canine mammary adenocarcinoma cell line and one mammary adenoma cell line showed significantly decreased viability after treatment, whereas the non-neoplastic cell line was resistant. We conclude that the reengineered anthrax toxin may be considered a targeted therapy for canine mammary neoplasms while preserving normal canine mammary epithelial cells.

Keywords: Anthrax; Canine; Mammary cancer; Metalloproteinase; Toxin.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Adenocarcinoma / veterinary
  • Adenoma / drug therapy
  • Adenoma / pathology
  • Adenoma / veterinary
  • Animals
  • Antigens, Bacterial* / pharmacology
  • Bacterial Toxins* / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dog Diseases* / drug therapy
  • Dogs
  • Epithelial Cells / drug effects
  • Female
  • Mammary Neoplasms, Animal* / drug therapy

Substances

  • anthrax toxin
  • Bacterial Toxins
  • Antigens, Bacterial