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

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

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

Arquivos

2-s2.0-85021670148.pdf (1.96 MB)

Data

2017-08-15

Autores

Gelaleti, Gabriela Bottaro

Borin, Thaiz Ferraz

Maschio-Signorini, Larissa Bazela

Moschetta, Marina Gobbe

Jardim-Perassi, Bruna Victorasso

Calvinho, Guilherme Berto

Facchini, Mariana Castilho

Viloria-Petit, Alicia M.

de Campos Zuccari, Debora Aparecida Pires

Tipo

Artigo

Direito de acesso

Acesso aberto

Resumo

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.