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: | Biblioteca Digital de Teses e Dissertações da 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 |
PCAM_5d04ecbe227a48589f145c3159d92e2d |
---|---|
oai_identifier_str |
oai:repositorio.sis.puc-campinas.edu.br:123456789/17228 |
network_acronym_str |
PCAM |
network_name_str |
Biblioteca Digital de Teses e Dissertações da PUC_CAMPINAS |
repository_id_str |
4886 |
spelling |
Godoy, Maria Carolina Ximenes deMacedo, Juliana AlvesGambero, AlessandraPontifícia Universidade Católica de Campinas (PUC-Campinas)2024-03-27T13:14:18Z2024-03-27T13:14:18Z2024-01-04http://repositorio.sis.puc-campinas.edu.br/xmlui/handle/123456789/17228472314747067740982648455169067347165708428659026Therapeutically 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.engPharmaceuticalsdasatinibquercetinellagic acidresveratrolsenotherapeuticcell senescenceResearching 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-5info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_CAMPINASinstname:Pontifícia Universidade Católica de Campinas (PUC-CAMPINAS)instacron:PUC_CAMPEscola de Ciências da VidaCiências da SaúdeOnlineNão se aplicaLICENSElicense.txtlicense.txttext/plain; charset=utf-80http://repositorio.sis.puc-campinas.edu.br/xmlui/bitstream/123456789/17228/2/license.txtd41d8cd98f00b204e9800998ecf8427eMD52ORIGINALGambero, Alessandra - Researching new drug combinations.pdfGambero, Alessandra - Researching new drug combinations.pdfapplication/pdf2516591http://repositorio.sis.puc-campinas.edu.br/xmlui/bitstream/123456789/17228/1/Gambero%2c%20Alessandra%20-%20Researching%20new%20drug%20combinations.pdf827f2a0751f2e6fdf12db65d2828e3c9MD51123456789/172282024-03-27 10:14:19.117oai:repositorio.sis.puc-campinas.edu.br:123456789/17228Biblioteca Digital de Teses e Dissertaçõeshttp://tede.bibliotecadigital.puc-campinas.edu.br:8080/jspui/http://tede.bibliotecadigital.puc-campinas.edu.br:8080/oai/requestsbi.bibliotecadigital@puc-campinas.edu.b||sbi.bibliotecadigital@puc-campinas.edu.bropendoar:48862024-03-27T13:14:19Biblioteca Digital de Teses e Dissertações da PUC_CAMPINAS - Pontifícia Universidade Católica de Campinas (PUC-CAMPINAS)false |
dc.title.pt_BR.fl_str_mv |
Researching new drug combinations with senolytic activity using senescent human lung fibroblasts MRC-5 cell line |
dc.title.alternative.pt_BR.fl_str_mv |
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.institution.pt_BR.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.accessioned.fl_str_mv |
2024-03-27T13:14:18Z |
dc.date.available.fl_str_mv |
2024-03-27T13:14:18Z |
dc.date.issued.fl_str_mv |
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 |
dc.identifier.lattes.pt_BR.fl_str_mv |
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.publisher.none.fl_str_mv |
Pharmaceuticals |
publisher.none.fl_str_mv |
Pharmaceuticals |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da 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 |
Biblioteca Digital de Teses e Dissertações da PUC_CAMPINAS |
collection |
Biblioteca Digital de Teses e Dissertações da PUC_CAMPINAS |
bitstream.url.fl_str_mv |
http://repositorio.sis.puc-campinas.edu.br/xmlui/bitstream/123456789/17228/2/license.txt http://repositorio.sis.puc-campinas.edu.br/xmlui/bitstream/123456789/17228/1/Gambero%2c%20Alessandra%20-%20Researching%20new%20drug%20combinations.pdf |
bitstream.checksum.fl_str_mv |
d41d8cd98f00b204e9800998ecf8427e 827f2a0751f2e6fdf12db65d2828e3c9 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da PUC_CAMPINAS - Pontifícia Universidade Católica de Campinas (PUC-CAMPINAS) |
repository.mail.fl_str_mv |
sbi.bibliotecadigital@puc-campinas.edu.b||sbi.bibliotecadigital@puc-campinas.edu.br |
_version_ |
1796790721360953344 |