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Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells
Pharmaceuticals, Volume: 14, Issue: 2, Start page: 91
Swansea University Author:
Gill Conway
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DOI (Published version): 10.3390/ph14020091
Abstract
Ursolic acid (UA) is a bioactive compound which has demonstrated therapeutic efficacy in a variety of cancer cell lines. UA activates various signalling pathways in Glioblastoma multiforme (GBM) and offers a promising starting point in drug discovery; however, understanding the relationship between...
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ISSN: | 1424-8247 |
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MDPI AG
2021
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v2 65440 2024-01-10 Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells e33e0ee5a076ad91fe6615117caa1800 0000-0002-5991-0960 Gill Conway Gill Conway true false 2024-01-10 BMS Ursolic acid (UA) is a bioactive compound which has demonstrated therapeutic efficacy in a variety of cancer cell lines. UA activates various signalling pathways in Glioblastoma multiforme (GBM) and offers a promising starting point in drug discovery; however, understanding the relationship between cell death and migration has yet to be elucidated. UA induces a dose dependent cytotoxic response demonstrated by flow cytometry and biochemical cytotoxicity assays. Inhibitor and fluorescent probe studies demonstrate that UA induces a caspase independent, JNK dependent, mechanism of cell death. Migration studies established that UA inhibits GBM collective cell migration in a time dependent manner that is independent of the JNK signalling pathway. Cytotoxicity induced by UA results in the formation of acidic vesicle organelles (AVOs), speculating the activation of autophagy. However, inhibitor and spectrophotometric analysis demonstrated that autophagy was not responsible for the formation of the AVOs. Confocal microscopy and isosurface visualisation determined co-localisation of lysosomes with the previously identified AVOs, thus providing evidence that lysosomes are likely to be playing a role in UA induced cell death. Collectively, our data identify that UA rapidly induces a lysosomal associated mechanism of cell death in addition to UA acting as an inhibitor of GBM collective cell migration. Journal Article Pharmaceuticals 14 2 91 MDPI AG 1424-8247 ursolic acid; cell death; migration; lysosomes; nutraceuticals 26 1 2021 2021-01-26 10.3390/ph14020091 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University This work is supported by the Irish Research Council IRCSET grant (G.E.C), Spanish Ministry of Economy and Competitiveness and European Regional Development Fund Grant number SAF2015-64123-P (C.B. and G.P.C). 2024-03-23T11:58:18.7988938 2024-01-10T15:29:02.3974706 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Gill Conway 0000-0002-5991-0960 1 Deimante Zizyte 2 Julie Rose Mae Mondala 0000-0002-9656-311x 3 Zhonglei He 4 Lorna Lynam 5 Mathilde Lecourt 0000-0003-3552-2100 6 Carlos Barcia 7 Orla Howe 0000-0002-5150-022x 8 James F. Curtin 0000-0002-9320-9254 9 65440__29810__bb3b8fa851224543855cbf413c5552a4.pdf 65440.VOR.pdf 2024-03-23T11:57:02.3420532 Output 3245866 application/pdf Version of Record true © 2021 by the authors.This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. true eng https://creativecommons.org/licenses/by/4.0/ |
title |
Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells |
spellingShingle |
Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells Gill Conway |
title_short |
Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells |
title_full |
Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells |
title_fullStr |
Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells |
title_full_unstemmed |
Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells |
title_sort |
Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells |
author_id_str_mv |
e33e0ee5a076ad91fe6615117caa1800 |
author_id_fullname_str_mv |
e33e0ee5a076ad91fe6615117caa1800_***_Gill Conway |
author |
Gill Conway |
author2 |
Gill Conway Deimante Zizyte Julie Rose Mae Mondala Zhonglei He Lorna Lynam Mathilde Lecourt Carlos Barcia Orla Howe James F. Curtin |
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Journal article |
container_title |
Pharmaceuticals |
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14 |
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91 |
publishDate |
2021 |
institution |
Swansea University |
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1424-8247 |
doi_str_mv |
10.3390/ph14020091 |
publisher |
MDPI AG |
college_str |
Faculty of Medicine, Health and Life Sciences |
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Faculty of Medicine, Health and Life Sciences |
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Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science |
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Ursolic acid (UA) is a bioactive compound which has demonstrated therapeutic efficacy in a variety of cancer cell lines. UA activates various signalling pathways in Glioblastoma multiforme (GBM) and offers a promising starting point in drug discovery; however, understanding the relationship between cell death and migration has yet to be elucidated. UA induces a dose dependent cytotoxic response demonstrated by flow cytometry and biochemical cytotoxicity assays. Inhibitor and fluorescent probe studies demonstrate that UA induces a caspase independent, JNK dependent, mechanism of cell death. Migration studies established that UA inhibits GBM collective cell migration in a time dependent manner that is independent of the JNK signalling pathway. Cytotoxicity induced by UA results in the formation of acidic vesicle organelles (AVOs), speculating the activation of autophagy. However, inhibitor and spectrophotometric analysis demonstrated that autophagy was not responsible for the formation of the AVOs. Confocal microscopy and isosurface visualisation determined co-localisation of lysosomes with the previously identified AVOs, thus providing evidence that lysosomes are likely to be playing a role in UA induced cell death. Collectively, our data identify that UA rapidly induces a lysosomal associated mechanism of cell death in addition to UA acting as an inhibitor of GBM collective cell migration. |
published_date |
2021-01-26T11:58:15Z |
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11.021648 |