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

Detalhes bibliográficos
Autor(a) principal: de Godoy, Bianca Lara Venâncio
Data de Publicação: 2023
Outros Autores: Moschetta-Pinheiro, Marina Gobbe, Chuffa, Luiz Gustavo de Almeida [UNESP], Pondé, Noam Falbel, Reiter, Russel J., Colombo, Jucimara, Zuccari, Debora Aparecida Pires de Campos [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.lfs.2023.121708
http://hdl.handle.net/11449/248758
Resumo: Aims: 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.
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spelling Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutationAlpelisibBreast CancerMDA-MB-453MelatoninPIK3CAT-47DAims: 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.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Faculdade de Medicina de São José do Rio PretoLaboratório de Investigação Molecular do Câncer (LIMC) Faculdade de Medicina de São José do Rio Preto – FAMERP, Av. Brigadeiro Faria Lima, 5416, SPPostgraduate Program in Health Sciences Faculdade de Medicina de São José do Rio Preto – FAMERP, Av. Brigadeiro Faria Lima, 5416, SPUniversidade Paulista – UNIP, SPDepartment of Structural and Functional Biology Anatomy Sector Instituto de Biociências de Botucatu – IBB/UNESP, SPIQVIA Biotech, SPDepartment of Cell Systems and Anatomy UT Health Long School of MedicineDepartment of Molecular Biology – FAMERP Collaborating Professor for Post-Graduate Program in Genetics – UNESP/IBILCE, SPDepartment of Structural and Functional Biology Anatomy Sector Instituto de Biociências de Botucatu – IBB/UNESP, SPDepartment of Molecular Biology – FAMERP Collaborating Professor for Post-Graduate Program in Genetics – UNESP/IBILCE, SPFaculdade de Medicina de São José do Rio Preto – FAMERPUniversidade Paulista – UNIPUniversidade Estadual Paulista (UNESP)IQVIA BiotechLong School of Medicinede Godoy, Bianca Lara VenâncioMoschetta-Pinheiro, Marina GobbeChuffa, Luiz Gustavo de Almeida [UNESP]Pondé, Noam FalbelReiter, Russel J.Colombo, JucimaraZuccari, Debora Aparecida Pires de Campos [UNESP]2023-07-29T13:52:54Z2023-07-29T13:52:54Z2023-07-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.lfs.2023.121708Life Sciences, v. 324.1879-06310024-3205http://hdl.handle.net/11449/24875810.1016/j.lfs.2023.1217082-s2.0-85154589591Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengLife Sciencesinfo:eu-repo/semantics/openAccess2023-07-29T13:52:54Zoai:repositorio.unesp.br:11449/248758Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-06T00:05:47.725511Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation
title Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation
spellingShingle Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation
de Godoy, Bianca Lara Venâncio
Alpelisib
Breast Cancer
MDA-MB-453
Melatonin
PIK3CA
T-47D
title_short Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation
title_full Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation
title_fullStr Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation
title_full_unstemmed Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation
title_sort Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation
author de Godoy, Bianca Lara Venâncio
author_facet de Godoy, Bianca Lara Venâncio
Moschetta-Pinheiro, Marina Gobbe
Chuffa, Luiz Gustavo de Almeida [UNESP]
Pondé, Noam Falbel
Reiter, Russel J.
Colombo, Jucimara
Zuccari, Debora Aparecida Pires de Campos [UNESP]
author_role author
author2 Moschetta-Pinheiro, Marina Gobbe
Chuffa, Luiz Gustavo de Almeida [UNESP]
Pondé, Noam Falbel
Reiter, Russel J.
Colombo, Jucimara
Zuccari, Debora Aparecida Pires de Campos [UNESP]
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Faculdade de Medicina de São José do Rio Preto – FAMERP
Universidade Paulista – UNIP
Universidade Estadual Paulista (UNESP)
IQVIA Biotech
Long School of Medicine
dc.contributor.author.fl_str_mv de Godoy, Bianca Lara Venâncio
Moschetta-Pinheiro, Marina Gobbe
Chuffa, Luiz Gustavo de Almeida [UNESP]
Pondé, Noam Falbel
Reiter, Russel J.
Colombo, Jucimara
Zuccari, Debora Aparecida Pires de Campos [UNESP]
dc.subject.por.fl_str_mv Alpelisib
Breast Cancer
MDA-MB-453
Melatonin
PIK3CA
T-47D
topic Alpelisib
Breast Cancer
MDA-MB-453
Melatonin
PIK3CA
T-47D
description Aims: 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.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-29T13:52:54Z
2023-07-29T13:52:54Z
2023-07-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.lfs.2023.121708
Life Sciences, v. 324.
1879-0631
0024-3205
http://hdl.handle.net/11449/248758
10.1016/j.lfs.2023.121708
2-s2.0-85154589591
url http://dx.doi.org/10.1016/j.lfs.2023.121708
http://hdl.handle.net/11449/248758
identifier_str_mv Life Sciences, v. 324.
1879-0631
0024-3205
10.1016/j.lfs.2023.121708
2-s2.0-85154589591
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Life Sciences
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
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