TY - JOUR
T1 - Efficacy of melatonin, IL-25 and siIL-17B in tumorigenesis-associated properties of breast cancer cell lines
AU - Gelaleti, Gabriela Bottaro
AU - Borin, Thaiz Ferraz
AU - Maschio-Signorini, Larissa Bazela
AU - Moschetta, Marina Gobbe
AU - Jardim-Perassi, Bruna Victorasso
AU - Calvinho, Guilherme Berto
AU - Facchini, Mariana Castilho
AU - Viloria-Petit, Alicia M.
AU - de Campos Zuccari, Debora Aparecida Pires
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2017/8/15
Y1 - 2017/8/15
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Breast cancer
KW - Interleukin-17B
KW - Interleukin-17E
KW - Interleukin-25
KW - Melatonin
KW - VEGF
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U2 - 10.1016/j.lfs.2017.06.013
DO - 10.1016/j.lfs.2017.06.013
M3 - Article
C2 - 28624391
AN - SCOPUS:85021670148
SN - 0024-3205
VL - 183
SP - 98
EP - 109
JO - Life sciences
JF - Life sciences
ER -