Ursolic acid impairs cellular lipid homeostasis and lysosomal membrane integrity in breast carcinoma cells
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | https://hdl.handle.net/1822/81276 |
Resumo: | 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. |
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Ursolic acid impairs cellular lipid homeostasis and lysosomal membrane integrity in breast carcinoma cellsAutophagyCationic amphiphilic drugsCell deathCancerLysosomal membrane permeabilizationUrsolic acidScience & TechnologyThe 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.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.This work was supported by grants from the Danish National Research Foundation (DNRF125), European Research Council (AdG340751), Danish Cancer Society (R167-A11061) and, Novo Nordisk Foundation (NNF19OC0054296), to M.J., K.M. was supported by the Independent Research Fund Denmark (6108–00542B) and Novo Nordisk Foundation (NNF17OC0029432).info:eu-repo/semantics/publishedVersionMultidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoFogde, Ditte L.Xavier, Cristina P. R.Balnyte, KristinaHolland, Lya K. K.Stahl-Meyer, KamillaDinant, ChristoffelCorcelle-Termeau, ElisabethPereira-Wilson, CristinaMaeda, KenjiJäättelä, Marja2022-12-142022-12-14T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/81276engFogde, 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/cells112440792073-440910.3390/cells11244079https://www.mdpi.com/journal/cellsinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-30T01:25:34Zoai:repositorium.sdum.uminho.pt:1822/81276Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:23:17.093494Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Ursolic acid impairs cellular lipid homeostasis and lysosomal membrane integrity in breast carcinoma cells |
| title |
Ursolic acid impairs cellular lipid homeostasis and lysosomal membrane integrity in breast carcinoma cells |
| spellingShingle |
Ursolic acid impairs cellular lipid homeostasis and lysosomal membrane integrity in breast carcinoma cells Fogde, Ditte L. Autophagy Cationic amphiphilic drugs Cell death Cancer Lysosomal membrane permeabilization Ursolic acid Science & Technology |
| title_short |
Ursolic acid impairs cellular lipid homeostasis and lysosomal membrane integrity in breast carcinoma cells |
| title_full |
Ursolic acid impairs cellular lipid homeostasis and lysosomal membrane integrity in breast carcinoma cells |
| title_fullStr |
Ursolic acid impairs cellular lipid homeostasis and lysosomal membrane integrity in breast carcinoma cells |
| title_full_unstemmed |
Ursolic acid impairs cellular lipid homeostasis and lysosomal membrane integrity in breast carcinoma cells |
| title_sort |
Ursolic acid impairs cellular lipid homeostasis and lysosomal membrane integrity in breast carcinoma cells |
| author |
Fogde, Ditte L. |
| author_facet |
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 |
| author_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidade do Minho |
| dc.contributor.author.fl_str_mv |
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 |
| dc.subject.por.fl_str_mv |
Autophagy Cationic amphiphilic drugs Cell death Cancer Lysosomal membrane permeabilization Ursolic acid Science & Technology |
| topic |
Autophagy Cationic amphiphilic drugs Cell death Cancer Lysosomal membrane permeabilization Ursolic acid Science & Technology |
| description |
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. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-12-14 2022-12-14T00:00:00Z |
| 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 |
https://hdl.handle.net/1822/81276 |
| url |
https://hdl.handle.net/1822/81276 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
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 2073-4409 10.3390/cells11244079 https://www.mdpi.com/journal/cells |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
| publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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