Melatonin and IL-25 modulate apoptosis and angiogenesis mediators in metastatic (CF-41) and non-metastatic (CMT-U229) canine mammary tumour cells

Vet Comp Oncol. 2017 Dec;15(4):1572-1584. doi: 10.1111/vco.12303. Epub 2017 Mar 20.

Abstract

Background: Melatonin has oncostatic actions and IL-25 is active in inflammatory processes that induce apoptosis in tumor cells AIM: The aim of this study was to evaluate melatonin and IL-25 in metastatic (CF-41) and non-metastatic (CMT-U229) canine mammary tumor cells cultured as monolayers and tridimensional structures.

Materials and methods: The cells were treated with melatonin, IL-25 and IL-17B silencing gene and performed cell viability, gene and protein expression of caspase-3 and VEGFA (Vascular endothelial growth factor A) and an apoptosis membrane protein array.

Results: Treatment with 1 mM of melatonin reduced cell viability of both tumor cell lines, all treatments alone and combined significantly increased caspase-3 cleaved and proteins involved in the apoptotic pathway and reduced pro-angiogenic VEGFA, confirming the effectiveness of these potential promising treatments.

Conclusion: This is the first study evaluating the potential use of these strategies in CF-41 and CMT-U229 cell lines and together encourages subsequent in vitro and in vivo studies for further exploration of clinical applications.

Keywords: angiogenesis; apoptosis; canine; interleukin-25; mammary tumour cells; melatonin.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dog Diseases / drug therapy*
  • Dog Diseases / pathology
  • Dogs
  • Female
  • Fluorescent Antibody Technique / veterinary
  • Gene Silencing
  • Interleukin-17 / pharmacology*
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / pathology
  • Melatonin / pharmacology*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Interleukin-17
  • Vascular Endothelial Growth Factor A
  • Caspase 3
  • Melatonin