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

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dc.contributor.authorGelaleti, Gabriela Bottaro [UNESP]
dc.contributor.authorBorin, Thaiz Ferraz
dc.contributor.authorMaschio-Signorini, Larissa Bazela
dc.contributor.authorMoschetta, Marina Gobbe
dc.contributor.authorJardim-Perassi, Bruna Victorasso
dc.contributor.authorCalvinho, Guilherme Berto
dc.contributor.authorFacchini, Mariana Castilho
dc.contributor.authorViloria-Petit, Alicia M.
dc.contributor.authorde Campos Zuccari, Debora Aparecida Pires [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionLaboratório de Investigação Molecular do Câncer (LIMC)
dc.contributor.institutionAugusta University
dc.contributor.institutionUniversity of Guelph
dc.date.accessioned2018-12-11T16:48:00Z
dc.date.available2018-12-11T16:48:00Z
dc.date.issued2017-08-15
dc.description.abstractMammary 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.en
dc.description.affiliationUniversidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP/IBILCE) Programa de Pós-Graduação em Genética, São José do Rio Preto
dc.description.affiliationFaculdade de Medicina de São José do Rio Preto (FAMERP) Laboratório de Investigação Molecular do Câncer (LIMC), São José do Rio Preto
dc.description.affiliationTumor Imaging Angiogenesis Laboratory Georgia Cancer Center Augusta University
dc.description.affiliationDepartment of Biomedical Sciences Ontario Veterinary College University of Guelph
dc.description.affiliationUnespUniversidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP/IBILCE) Programa de Pós-Graduação em Genética, São José do Rio Preto
dc.description.sponsorshipFaculdade de Medicina de São José do Rio Preto
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 2012/02128-1
dc.description.sponsorshipIdFAPESP: 2012/06098-0
dc.format.extent98-109
dc.identifierhttp://dx.doi.org/10.1016/j.lfs.2017.06.013
dc.identifier.citationLife Sciences, v. 183, p. 98-109.
dc.identifier.doi10.1016/j.lfs.2017.06.013
dc.identifier.file2-s2.0-85021670148.pdf
dc.identifier.issn1879-0631
dc.identifier.issn0024-3205
dc.identifier.scopus2-s2.0-85021670148
dc.identifier.urihttp://hdl.handle.net/11449/169878
dc.language.isoeng
dc.relation.ispartofLife Sciences
dc.relation.ispartofsjr1,071
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectApoptosis
dc.subjectBreast cancer
dc.subjectInterleukin-17B
dc.subjectInterleukin-17E
dc.subjectInterleukin-25
dc.subjectMelatonin
dc.subjectVEGF
dc.titleEfficacy of melatonin, IL-25 and siIL-17B in tumorigenesis-associated properties of breast cancer cell linesen
dc.typeArtigo

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