Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , |
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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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) |
repository.mail.fl_str_mv |
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1808129581932085248 |