Researching new drug combinations with senolytic activity using senescent human lung fibroblasts MRC-5 cell line
Título alternativo
Pesquisa de novas combinações de medicamentos com atividade senolítica utilizando fibroblastos pulmonares humanos senescentes da linhagem celular MRC-5Autor
Godoy, Maria Carolina Ximenes de
Macedo, Juliana Alves
Gambero, Alessandra
Data de publicação
04/01/2024Tipo de conteúdo
ArtigoPrograma de Pós-Graduação
Ciências da SaúdeDireitos de acesso
Acesso abertoMetadados
Mostrar registro completoResumo
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.
Palavras-chave
DasatinibQuercetin
Ellagic acid
Resveratrol
Senotherapeutic
Cell senescence