Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells
Conway, Gillian E. (In-Vitro Toxicology Group, Institute of Life Science, Swansea University Medical School)
Zizyte, Deimante (School of Food Science and Environmental Health, Technological University Dublin)
Mondala, Julie Rose Mae (School of Food Science and Environmental Health, Technological University Dublin)
He, Zhonglei (Environmental Sustainability and Health Institute (ESHI) and FOCAS Research Institute, Technological University Dublin)
Lynam, Lorna (School of Food Science and Environmental Health, Technological University Dublin)
Lecourt, Mathilde (School of Food Science and Environmental Health, Technological University Dublin)
Barcia, Carlos (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Howe, Orla (School of Biological Sciences and Health Sciences, Technological University Dublin)
Curtin, James (Dublin Institute of Technology. School of Food Science and Environmental Health)

Fecha:	2021
Resumen:	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. https://doi. org/10. 13039/5011000033295https://doi. org/10. 13039/5011000033293https://doi. org/10. 13039/5011000033296https://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329_https://doi. org/10. 13039/501100003329_https://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329 $h ttps://doi. org/10. 13039/501100003329ahttps://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329Mhttps://doi. org/10. 13039/501100003329ihttps://doi. org/10. 13039/501100003329nhttps://doi. org/10. 13039/501100003329ihttps://doi. org/10. 13039/501100003329shttps://doi. org/10. 13039/501100003329thttps://doi. org/10. 13039/501100003329ehttps://doi. org/10. 13039/501100003329rhttps://doi. org/10. 13039/501100003329ihttps://doi. org/10. 13039/501100003329ohttps://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329dhttps://doi. org/10. 13039/501100003329ehttps://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329Ehttps://doi. org/10. 13039/501100003329chttps://doi. org/10. 13039/501100003329ohttps://doi. org/10. 13039/501100003329nhttps://doi. org/10. 13039/501100003329ohttps://doi. org/10. 13039/501100003329mhttps://doi. org/10. 13039/501100003329íhttps://doi. org/10. 13039/501100003329ahttps://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329yhttps://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329Chttps://doi. org/10. 13039/501100003329ohttps://doi. org/10. 13039/501100003329mhttps://doi. org/10. 13039/501100003329phttps://doi. org/10. 13039/501100003329ehttps://doi. org/10. 13039/501100003329thttps://doi. org/10. 13039/501100003329ihttps://doi. org/10. 13039/501100003329thttps://doi. org/10. 13039/501100003329ihttps://doi. org/10. 13039/501100003329vhttps://doi. org/10. 13039/501100003329ihttps://doi. org/10. 13039/501100003329dhttps://doi. org/10. 13039/501100003329ahttps://doi. org/10. 13039/501100003329dhttps://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329 $h ttps://doi. org/10. 13039/501100003329dhttps://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329 $h ttps://doi. org/10. 13039/501100003329fhttps://doi. org/10. 13039/501100003329 https://doi. org/10. 13039/501100003329Shttps://doi. org/10. 13039/501100003329Ahttps://doi. org/10. 13039/501100003329Fhttps://doi. org/10. 13039/5011000033292https://doi. org/10. 13039/5011000033290https://doi. org/10. 13039/5011000033291https://doi. org/10. 13039/5011000033295https://doi. org/10. 13039/501100003329-https://doi. org/10. 13039/5011000033296https://doi. org/10. 13039/5011000033294https://doi. org/10. 13039/5011000033291https://doi. org/10. 13039/5011000033292https://doi. org/10. 13039/5011000033293https://doi. org/10. 13039/501100003329-https://doi. org/10. 13039/501100003329Phttps://doi. org/10. 13039/501100003329.
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Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Ursolic acid ; Cell death ; Migration ; Lysosomes ; Nutraceuticals
Publicado en:	Pharmaceuticals, Vol. 14 (january 2021) , ISSN 1424-8247

DOI: 10.3390/ph14020091
PMID: 33530486

16 p, 3.1 MB

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