Efficacy of melatonin, IL-25 and siIL-17B in tumorigenesis-associated properties of breast cancer cell lines

Gabriela Bottaro Gelaleti, Thaiz Ferraz Borin, Larissa Bazela Maschio-Signorini, Marina Gobbe Moschetta, Bruna Victorasso Jardim-Perassi, Guilherme Berto Calvinho, Mariana Castilho Facchini, Alicia M. Viloria-Petit, Debora Aparecida Pires de Campos Zuccari

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Mammary tumorigenesis can be modulated by melatonin, which has oncostatic action mediated by multiple mechanisms, including the inhibition of the activity of transcription factors such as NF-κB and modulation of interleukins (ILs) expression. IL-25 is an active cytokine that induces apoptosis in tumor cells due to differential expression of its receptor (IL-17RB). IL-17B competes with IL-25 for binding to IL-17RB in tumor cells, promoting tumorigenesis. This study purpose is to address the possibility of engaging IL-25/IL-17RB signaling to enhance the effect of melatonin on breast cancer cells. Breast cancer cell lines were cultured monolayers and 3D structures and treated with melatonin, IL-25, siIL-17B, each alone or in combination. Cell viability, gene and protein expression of caspase-3, cleaved caspase-3 and VEGF-A were performed by qPCR and immunofluorescence. In addition, an apoptosis membrane array was performed in metastatic cells. Treatments with melatonin and IL-25 significantly reduced tumor cells viability at 1 mM and 1 ng/mL, respectively, but did not alter cell viability of a non-tumorigenic epithelial cell line (MCF-10A). All treatments, alone and combined, significantly increased cleaved caspase-3 in tumor cells grown as monolayers and 3D structures (p < 0.05). Semi-quantitative analysis of apoptosis pathway proteins showed an increase of CYTO-C, DR6, IGFBP-3, IGFBP-5, IGFPB-6, IGF-1, IGF-1R, Livin, P21, P53, TNFRII, XIAP and hTRA proteins and reduction of caspase-3 (p < 0.05) after melatonin treatment. All treatments reduced VEGF-A protein expression in tumor cells (p < 0.05). Our results suggest therapeutic potential, with oncostatic effectiveness, pro-apoptotic and anti-angiogenic properties for melatonin and IL-25-driven signaling in breast cancer cells.

Original languageEnglish (US)
Pages (from-to)98-109
Number of pages12
JournalLife sciences
Volume183
DOIs
Publication statusPublished - Aug 15 2017

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Keywords

  • Apoptosis
  • Breast cancer
  • Interleukin-17B
  • Interleukin-17E
  • Interleukin-25
  • Melatonin
  • VEGF

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Gelaleti, G. B., Borin, T. F., Maschio-Signorini, L. B., Moschetta, M. G., Jardim-Perassi, B. V., Calvinho, G. B., ... de Campos Zuccari, D. A. P. (2017). Efficacy of melatonin, IL-25 and siIL-17B in tumorigenesis-associated properties of breast cancer cell lines. Life sciences, 183, 98-109. https://doi.org/10.1016/j.lfs.2017.06.013