Publicação

Ursolic acid impairs cellular lipid homeostasis and lysosomal membrane integrity in breast carcinoma cells

Ver documento

Detalhes bibliográficos
Resumo:Cancer is one of the leading causes of death worldwide, thus the search for new cancer therapies is of utmost importance. Ursolic acid is a naturally occurring pentacyclic triterpene with a wide range of pharmacological activities including anti-inflammatory and anti-neoplastic effects. The latter has been assigned to its ability to promote apoptosis and inhibit cancer cell proliferation by poorly defined mechanisms. In this report, we identify lysosomes as the essential targets of the anti-cancer activity of ursolic acid. The treatment of MCF7 breast cancer cells with ursolic acid elevates lysosomal pH, alters the cellular lipid profile, and causes lysosomal membrane permeabilization and leakage of lysosomal enzymes into the cytosol. Lysosomal membrane permeabilization precedes the essential hallmarks of apoptosis placing it as an initial event in the cascade of effects induced by ursolic acid. The disruption of the lysosomal function impairs the autophagic pathway and likely partakes in the mechanism by which ursolic acid kills cancer cells. Furthermore, we find that combining treatment with ursolic acid and cationic amphiphilic drugs can significantly enhance the degree of lysosomal membrane permeabilization and cell death in breast cancer cells.
Autores principais:Fogde, Ditte L.
Outros Autores:Xavier, Cristina P. R.; Balnyte, Kristina; Holland, Lya K. K.; Stahl-Meyer, Kamilla; Dinant, Christoffel; Corcelle-Termeau, Elisabeth; Pereira-Wilson, Cristina; Maeda, Kenji; Jäättelä, Marja
Assunto:Autophagy Cationic amphiphilic drugs Cell death Cancer Lysosomal membrane permeabilization Ursolic acid
Ano:2022
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho

Registos relacionados

Registos relacionados