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Article

Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells

1
School of Food Science and Environmental Health, Technological University Dublin, D01 HV58 Dublin, Ireland
2
Environmental Sustainability and Health Institute (ESHI) and FOCAS Research Institute, Technological University Dublin, D08 CKP1 Dublin, Ireland
3
In-Vitro Toxicology Group, Institute of Life Science, Swansea University Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, UK
4
Institut de Neurociències, Department of Biochemistry and Molecular Biology, School of Medicine, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
5
School of Biological Sciences and Health Sciences, Technological University Dublin, D08 NF82 Dublin, Ireland
*
Authors to whom correspondence should be addressed.
Academic Editor: Paulo Santos
Pharmaceuticals 2021, 14(2), 91; https://doi.org/10.3390/ph14020091
Received: 16 December 2020 / Revised: 19 January 2021 / Accepted: 20 January 2021 / Published: 26 January 2021
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants)
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. View Full-Text
Keywords: ursolic acid; cell death; migration; lysosomes; nutraceuticals ursolic acid; cell death; migration; lysosomes; nutraceuticals
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MDPI and ACS Style

Conway, G.E.; Zizyte, D.; Mondala, J.R.M.; He, Z.; Lynam, L.; Lecourt, M.; Barcia, C.; Howe, O.; Curtin, J.F. Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells. Pharmaceuticals 2021, 14, 91. https://doi.org/10.3390/ph14020091

AMA Style

Conway GE, Zizyte D, Mondala JRM, He Z, Lynam L, Lecourt M, Barcia C, Howe O, Curtin JF. Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells. Pharmaceuticals. 2021; 14(2):91. https://doi.org/10.3390/ph14020091

Chicago/Turabian Style

Conway, Gillian E., Deimante Zizyte, Julie R.M. Mondala, Zhonglei He, Lorna Lynam, Mathilde Lecourt, Carlos Barcia, Orla Howe, and James F. Curtin 2021. "Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells" Pharmaceuticals 14, no. 2: 91. https://doi.org/10.3390/ph14020091

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