Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/81276
Título: | Ursolic acid impairs cellular lipid homeostasis and lysosomal membrane integrity in breast carcinoma cells |
Autor(es): | Fogde, Ditte L. 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 |
Palavras-chave: | Autophagy Cationic amphiphilic drugs Cell death Cancer Lysosomal membrane permeabilization Ursolic acid |
Data: | 14-Dez-2022 |
Editora: | Multidisciplinary Digital Publishing Institute (MDPI) |
Revista: | Cells |
Citação: | Fogde, D.L.; Xavier, C.P.R.; Balnytė, K.; Holland, L.K.K.; Stahl-Meyer, K.; Dinant, C.; Corcelle-Termeau, E.; Pereira-Wilson, C.; Maeda, K.; Jäättelä, M. Ursolic Acid Impairs Cellular Lipid Homeostasis and Lysosomal Membrane Integrity in Breast Carcinoma Cells. Cells 2022, 11, 4079. https://doi.org/10.3390/cells11244079 |
Resumo(s): | 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. |
Tipo: | Artigo |
Descrição: | The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cells11244079/s1, Figure S1: UA kills MCF7 cells partly through apoptosis; Figure S2: UA causes LC3 puncta formation in MCF7 and HCT15 cells; Figure S3: UA causes LMP prior to MOMP and alters lysosomal localization in HeLa cells; Figure S4: Additional lipidomics data; Table S1: List of resources; Table S2: Internal lipid and drug standards; Table S3: Precursor ion, fragment ion, and neutral loss for lipid identification; Table S4: All experiments. |
URI: | https://hdl.handle.net/1822/81276 |
DOI: | 10.3390/cells11244079 |
e-ISSN: | 2073-4409 |
Versão da editora: | https://www.mdpi.com/journal/cells |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series DBio - Artigos/Papers |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
---|---|---|---|---|
document_55989_1.pdf | 3,8 MB | Adobe PDF | Ver/Abrir |
Este trabalho está licenciado sob uma Licença Creative Commons