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Efficacy of melatonin, IL-25 and siIL-17B in tumorigenesis-associated properties of breast cancer cell lines.
- Source :
-
Life sciences [Life Sci] 2017 Aug 15; Vol. 183, pp. 98-109. Date of Electronic Publication: 2017 Jun 15. - Publication Year :
- 2017
-
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 1mM and 1ng/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.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Apoptosis physiology
Breast Neoplasms genetics
Cell Line, Tumor
Cell Survival physiology
Female
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic
Humans
Interleukin-17 administration & dosage
Melatonin administration & dosage
Melatonin pharmacology
Neovascularization, Pathologic metabolism
Polymerase Chain Reaction
Receptors, Interleukin-17
Signal Transduction physiology
Vascular Endothelial Growth Factor A genetics
Breast Neoplasms pathology
Interleukin-17 metabolism
Melatonin metabolism
Receptors, Interleukin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 183
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 28624391
- Full Text :
- https://doi.org/10.1016/j.lfs.2017.06.013