Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation

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dc.contributor.authorde Godoy, Bianca Lara Venâncio
dc.contributor.authorMoschetta-Pinheiro, Marina Gobbe
dc.contributor.authorChuffa, Luiz Gustavo de Almeida [UNESP]
dc.contributor.authorPondé, Noam Falbel
dc.contributor.authorReiter, Russel J.
dc.contributor.authorColombo, Jucimara
dc.contributor.authorZuccari, Debora Aparecida Pires de Campos [UNESP]
dc.contributor.institutionFaculdade de Medicina de São José do Rio Preto – FAMERP
dc.contributor.institutionUniversidade Paulista – UNIP
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionIQVIA Biotech
dc.contributor.institutionLong School of Medicine
dc.date.accessioned2023-07-29T13:52:54Z
dc.date.available2023-07-29T13:52:54Z
dc.date.issued2023-07-01
dc.description.abstractAims: Breast cancer (BC) presents high mortality rate and about 25–46 % have mutation in the PIK3CA gene. Alpelisib is a PI3K inhibitor that acts on p110α, which is a subunit of the PI3K protein. The melatonin shown important anti-neoplastic effects and may increase the effectiveness of chemotherapy. This study evaluated the synergistic action of Alpelisib and Melatonin in BC lines carrying the H1047R mutation in PIK3CA, relative to the cellular dynamics and the PI3K/AKT/mTOR pathway. Main methods: MDA-MB-468 (triple-ernegative), MDA-MB-453 (H1047R PIK3CA, HER2+) and T-47D cells (H1047R PIK3CA, ER+/PR+) were divided into four treatment groups: control; Melatonin (1 mM); Alpelisib (1 μM); and Alpelisib (1 μM) + Melatonin (1 mM). Cell viability and migration were investigated using the MTT assay and Transwell assay, respectively. Protein expression of PI3K, p-AKT, mTOR, HIF-1α, and caspase-3, was verified using immunocytochemistry. Key findings: MTT assay revealed that MDA-MB-453 and T-47D showed reduction in cell viability in all groups, especially in the MDA-MB-453 treated with Melatonin + Alpelisib. MDA-MB-468 presents reduction in cell migration only with Melatonin, while in the lines with mutation, the treatment of Melatonin + Alpelisib caused inhibition of cell migration. PI3K, p-AKT, mTOR and HIF-1α were inhibited after treatment with Melatonin + Alpelisib in MDA-MB-453 and T-47D lines. The expression of caspase-3 increased in all groups in MDA-MB-453 and T-47D cells, being the increase more pronounced in the Melatonin + Alpelisib group. Significance: These results indicate that the combined use of Melatonin and Alpelisib may be more effective in inhibiting BC in women carrying the PIK3CA gene mutation than either treatment alone.en
dc.description.affiliationLaboratório de Investigação Molecular do Câncer (LIMC) Faculdade de Medicina de São José do Rio Preto – FAMERP, Av. Brigadeiro Faria Lima, 5416, SP
dc.description.affiliationPostgraduate Program in Health Sciences Faculdade de Medicina de São José do Rio Preto – FAMERP, Av. Brigadeiro Faria Lima, 5416, SP
dc.description.affiliationUniversidade Paulista – UNIP, SP
dc.description.affiliationDepartment of Structural and Functional Biology Anatomy Sector Instituto de Biociências de Botucatu – IBB/UNESP, SP
dc.description.affiliationIQVIA Biotech, SP
dc.description.affiliationDepartment of Cell Systems and Anatomy UT Health Long School of Medicine
dc.description.affiliationDepartment of Molecular Biology – FAMERP Collaborating Professor for Post-Graduate Program in Genetics – UNESP/IBILCE, SP
dc.description.affiliationUnespDepartment of Structural and Functional Biology Anatomy Sector Instituto de Biociências de Botucatu – IBB/UNESP, SP
dc.description.affiliationUnespDepartment of Molecular Biology – FAMERP Collaborating Professor for Post-Graduate Program in Genetics – UNESP/IBILCE, SP
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFaculdade de Medicina de São José do Rio Preto
dc.identifierhttp://dx.doi.org/10.1016/j.lfs.2023.121708
dc.identifier.citationLife Sciences, v. 324.
dc.identifier.doi10.1016/j.lfs.2023.121708
dc.identifier.issn1879-0631
dc.identifier.issn0024-3205
dc.identifier.scopus2-s2.0-85154589591
dc.identifier.urihttp://hdl.handle.net/11449/248758
dc.language.isoeng
dc.relation.ispartofLife Sciences
dc.sourceScopus
dc.subjectAlpelisib
dc.subjectBreast Cancer
dc.subjectMDA-MB-453
dc.subjectMelatonin
dc.subjectPIK3CA
dc.subjectT-47D
dc.titleSynergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutationen
dc.typeArtigo

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