Researching new drug combinations with senolytic activity using senescent human lung fibroblasts MRC-5 cell line
Autor(a) principal: | |
---|---|
Data de Publicação: | 2024 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional PUC-Campinas |
Texto Completo: | http://repositorio.sis.puc-campinas.edu.br/xmlui/handle/123456789/17228 |
Resumo: | Therapeutically targeting senescent cells seems to be an interesting perspective in treating chronic lung diseases, which are often associated with human aging. The combination of the drug dasatinib and the polyphenol quercetin is used in clinical trials as a senolytic, and the first results point to the relief of physical dysfunction in patients with idiopathic pulmonary fibrosis. In this work, we tested new combinations of drugs and polyphenols, looking for senolytic activity using human lung fibroblasts (MRC-5 cell line) with induced senescence. We researched drugs, such as azithromycin, rapamycin, metformin, FK-506, aspirin, and dasatinib combined with nine natural polyphenols, namely caffeic acid, chlorogenic acid, ellagic acid, ferulic acid, gallic acid, epicatechin, hesperidin, quercetin, and resveratrol. We found new effective senolytic combinations with dasatinib and ellagic acid and dasatinib and resveratrol. Both drug combinations increased apoptosis, reduced BCL-2 expression, and increased caspase activity in senescent MRC-5 cells. Ellagic acid senolytic activity was more potent than quercetin, and resveratrol counteracted inflammatory cytokine release during senolysis in vitro. In conclusion, dasatinib and ellagic acid and dasatinib and resveratrol present in vitro senolytic potential like that observed for the combination in clinical trials of dasatinib and quercetin, and maybe they could be future alternatives in the senotherapeutic field. |
id |
PUC_CAMP-5_5d04ecbe227a48589f145c3159d92e2d |
---|---|
oai_identifier_str |
oai:repositorio.sis.puc-campinas.edu.br:123456789/17228 |
network_acronym_str |
PUC_CAMP-5 |
network_name_str |
Repositório Institucional PUC-Campinas |
repository_id_str |
|
spelling |
Researching new drug combinations with senolytic activity using senescent human lung fibroblasts MRC-5 cell linePesquisa de novas combinações de medicamentos com atividade senolítica utilizando fibroblastos pulmonares humanos senescentes da linhagem celular MRC-5dasatinibquercetinellagic acidresveratrolsenotherapeuticcell senescenceTherapeutically targeting senescent cells seems to be an interesting perspective in treating chronic lung diseases, which are often associated with human aging. The combination of the drug dasatinib and the polyphenol quercetin is used in clinical trials as a senolytic, and the first results point to the relief of physical dysfunction in patients with idiopathic pulmonary fibrosis. In this work, we tested new combinations of drugs and polyphenols, looking for senolytic activity using human lung fibroblasts (MRC-5 cell line) with induced senescence. We researched drugs, such as azithromycin, rapamycin, metformin, FK-506, aspirin, and dasatinib combined with nine natural polyphenols, namely caffeic acid, chlorogenic acid, ellagic acid, ferulic acid, gallic acid, epicatechin, hesperidin, quercetin, and resveratrol. We found new effective senolytic combinations with dasatinib and ellagic acid and dasatinib and resveratrol. Both drug combinations increased apoptosis, reduced BCL-2 expression, and increased caspase activity in senescent MRC-5 cells. Ellagic acid senolytic activity was more potent than quercetin, and resveratrol counteracted inflammatory cytokine release during senolysis in vitro. In conclusion, dasatinib and ellagic acid and dasatinib and resveratrol present in vitro senolytic potential like that observed for the combination in clinical trials of dasatinib and quercetin, and maybe they could be future alternatives in the senotherapeutic field.PharmaceuticalsPontifícia Universidade Católica de Campinas (PUC-Campinas)Godoy, Maria Carolina Ximenes deMacedo, Juliana AlvesGambero, Alessandra2024-03-27T13:14:18Z2024-03-27T13:14:18Z2024-01-04info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://repositorio.sis.puc-campinas.edu.br/xmlui/handle/123456789/17228472314747067740982648455169067347165708428659026enginfo:eu-repo/semantics/openAccessreponame:Repositório Institucional PUC-Campinasinstname:Pontifícia Universidade Católica de Campinas (PUC-CAMPINAS)instacron:PUC_CAMP2024-03-27T13:14:19Zoai:repositorio.sis.puc-campinas.edu.br:123456789/17228Repositório InstitucionalPRIhttps://repositorio.sis.puc-campinas.edu.br/oai/requestsbi.bibliotecadigital@puc-campinas.edu.bropendoar:2024-03-27T13:14:19Repositório Institucional PUC-Campinas - Pontifícia Universidade Católica de Campinas (PUC-CAMPINAS)false |
dc.title.none.fl_str_mv |
Researching new drug combinations with senolytic activity using senescent human lung fibroblasts MRC-5 cell line Pesquisa de novas combinações de medicamentos com atividade senolítica utilizando fibroblastos pulmonares humanos senescentes da linhagem celular MRC-5 |
title |
Researching new drug combinations with senolytic activity using senescent human lung fibroblasts MRC-5 cell line |
spellingShingle |
Researching new drug combinations with senolytic activity using senescent human lung fibroblasts MRC-5 cell line Godoy, Maria Carolina Ximenes de dasatinib quercetin ellagic acid resveratrol senotherapeutic cell senescence |
title_short |
Researching new drug combinations with senolytic activity using senescent human lung fibroblasts MRC-5 cell line |
title_full |
Researching new drug combinations with senolytic activity using senescent human lung fibroblasts MRC-5 cell line |
title_fullStr |
Researching new drug combinations with senolytic activity using senescent human lung fibroblasts MRC-5 cell line |
title_full_unstemmed |
Researching new drug combinations with senolytic activity using senescent human lung fibroblasts MRC-5 cell line |
title_sort |
Researching new drug combinations with senolytic activity using senescent human lung fibroblasts MRC-5 cell line |
author |
Godoy, Maria Carolina Ximenes de |
author_facet |
Godoy, Maria Carolina Ximenes de Macedo, Juliana Alves Gambero, Alessandra |
author_role |
author |
author2 |
Macedo, Juliana Alves Gambero, Alessandra |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Pontifícia Universidade Católica de Campinas (PUC-Campinas) |
dc.contributor.author.fl_str_mv |
Godoy, Maria Carolina Ximenes de Macedo, Juliana Alves Gambero, Alessandra |
dc.subject.por.fl_str_mv |
dasatinib quercetin ellagic acid resveratrol senotherapeutic cell senescence |
topic |
dasatinib quercetin ellagic acid resveratrol senotherapeutic cell senescence |
description |
Therapeutically targeting senescent cells seems to be an interesting perspective in treating chronic lung diseases, which are often associated with human aging. The combination of the drug dasatinib and the polyphenol quercetin is used in clinical trials as a senolytic, and the first results point to the relief of physical dysfunction in patients with idiopathic pulmonary fibrosis. In this work, we tested new combinations of drugs and polyphenols, looking for senolytic activity using human lung fibroblasts (MRC-5 cell line) with induced senescence. We researched drugs, such as azithromycin, rapamycin, metformin, FK-506, aspirin, and dasatinib combined with nine natural polyphenols, namely caffeic acid, chlorogenic acid, ellagic acid, ferulic acid, gallic acid, epicatechin, hesperidin, quercetin, and resveratrol. We found new effective senolytic combinations with dasatinib and ellagic acid and dasatinib and resveratrol. Both drug combinations increased apoptosis, reduced BCL-2 expression, and increased caspase activity in senescent MRC-5 cells. Ellagic acid senolytic activity was more potent than quercetin, and resveratrol counteracted inflammatory cytokine release during senolysis in vitro. In conclusion, dasatinib and ellagic acid and dasatinib and resveratrol present in vitro senolytic potential like that observed for the combination in clinical trials of dasatinib and quercetin, and maybe they could be future alternatives in the senotherapeutic field. |
publishDate |
2024 |
dc.date.none.fl_str_mv |
2024-03-27T13:14:18Z 2024-03-27T13:14:18Z 2024-01-04 |
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://repositorio.sis.puc-campinas.edu.br/xmlui/handle/123456789/17228 4723147470677409 8264845516906734 7165708428659026 |
url |
http://repositorio.sis.puc-campinas.edu.br/xmlui/handle/123456789/17228 |
identifier_str_mv |
4723147470677409 8264845516906734 7165708428659026 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Pharmaceuticals |
publisher.none.fl_str_mv |
Pharmaceuticals |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional PUC-Campinas instname:Pontifícia Universidade Católica de Campinas (PUC-CAMPINAS) instacron:PUC_CAMP |
instname_str |
Pontifícia Universidade Católica de Campinas (PUC-CAMPINAS) |
instacron_str |
PUC_CAMP |
institution |
PUC_CAMP |
reponame_str |
Repositório Institucional PUC-Campinas |
collection |
Repositório Institucional PUC-Campinas |
repository.name.fl_str_mv |
Repositório Institucional PUC-Campinas - Pontifícia Universidade Católica de Campinas (PUC-CAMPINAS) |
repository.mail.fl_str_mv |
sbi.bibliotecadigital@puc-campinas.edu.br |
_version_ |
1798415785421438976 |