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

  • G. B. Gelaleti
    ,
  • T. F. Borin
    ,
  • L. B. Maschio-Signorini
    ,
  • M. G. Moschetta
    ,
  • E. Hellmén
    ,
  • A. M. Viloria-Petit(corresponding author)
*Corresponding author for this work
  • Faculdade de Medicina de São José do Rio Preto
    ,
  • Universidade Estadual Paulista Júlio de Mesquita Filho
    ,
  • Augusta University
    ,
  • Swedish University of Agricultural Sciences
    ,
  • University of Guelph
Scholary Output:
Contribution to journal
Article
Peer-review

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.

Publication Information

Output type

Scholary Output:
Contribution to journal
Article
Peer-review

Original language

English (US)

Pages from-to (Number of pages)

Pages 1572-1584 (13 pages)

Journal (Volume, Issue Number)

Veterinary and Comparative Oncology (Volume 15, Issue 4)

Publication milestones

  • Published - 12/2017

Publication status

Published - 12/2017

ISSN

1476-5810

Publication IDs

  • Scopus: 85016392441
  • PubMed: 28322030

Publication metrics

Metrics

Fractional count
1
Fractional count
0.14
Fractional count
6
Fractional count
0.86
Fractional count
1
Fractional count
1
Scopus
citations
SciVal
FWCI
1.65
SciVal
Author count
7
SciVal
citations
8
SciVal
Paper percentile
71

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Captures
52
Citation count
16

Funding Details

We thank Camila Leonel, Lívia Carvalho Ferreira and Gustavo Rodrigues Martins who participated in writing and editing of the manuscript, and Dr. Patricia Simone Leite Vilamaior for helping in capture and processing of 3D acquiring images in confocal microscope and associated software (ZEISS, model LSM 710, software ZEN 2010). Fundacao de Amparo a Pesquisa do Estado de Sao Paulo—FAPESP (grants no. 2012/06098-0 and 2012/02128-1) funded this research. The Laboratory of Molecular Research in Cancer/Laboratório de Investigação Molecular do Câncer (LIMC) and Laboratory for Integrated Study of the Mechanisms of Breast Cancer Invasion and Metastasis (University of Guelph, Ontario) provided the infrastructure to carry out this project; the latter funded by a Canadian Foundation for Innovation (CFI) and Ministry of Research Infrastructure (MRI, Ontario) grant to A.V.P. Author declares no interest conflict. G.B.G. designed the study, carried out the cell lines culture assays, performed the gene silencing and qRT-PCR assay, the immunofluorescence staining, the statistical analysis and drafted the manuscript. T.F.B. participated to design and performed the gene silencing and qRT-PCR assay and revised the manuscript. L.B.M. carried out the membrane array and analysis of results. M.G.M. carried out the cell viability assay, contributed to the interpretation of results and revised the manuscript. EV assigned CMT-U229 cell line, helped with maintenance of monolayer cell lines, interpretation of results and revised the manuscript. A.M.V. supervised the research, helped in immunofluorescence staining, helped with interpretation of results and drafted the manuscript. D.A.P.C.Z. conceived and designed the study, coordinated the research, performed interpretation of results and drafted the manuscript. All authors read and approved all aspects of the final manuscript.