Cold atmospheric plasma induces accumulation of lysosomes and caspase-independent cell death in U373MG glioblastoma multiforme cells
Conway, Gillian E. (Technological University Dublin. School of Food Science & Environmental Health)
He, Zhonglei (Technological University Dublin. Environmental Sustainability & Health Institute)
Hutanu, Ana Lacramioara (Trinity College Dublin. School of Biochemistry & Immunology)
Cribaro, eorge Paul (Universitat Autònoma de Barcelona. Institut de Neurociències)
Manaloto, Eline (Technological University Dublin. Environmental Sustainability & Health Institute)
Casey, Alan (FOCAS Research Institute)
Traynor, Damien (FOCAS Research Institute)
Milosavljevic, Vladimir (Technological University Dublin. School of Physics & Clinical & Optometric Sciences)
Howe, Orla (FOCAS Research Institute)
Barcia, Carlos (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Murray, James T. (Trinity College Dublin. School of Biochemistry & Immunology)
Cullen, Patrick J. (University of Sydney. School of Chemical and Biomolecular Engineering)
Curtin, James (FOCAS Research Institute)

Data:	2019
Resum:	Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma treated cells that stained positive with acridine orange. Western immunoblotting confirmed that autophagy is not activated following plasma treatment. Acridine orange intensity correlates closely with the lysosomal marker Lyso TrackerTM Deep Red. Further investigation using isosurface visualisation of confocal imaging confirmed that lysosomal accumulation occurs in plasma treated cells. The accumulation of lysosomes was associated with concomitant cell death following plasma treatment. In conclusion, we observed rapid accumulation of acidic vesicles and cell death following CAP treatment in GBM cells. We found no evidence that either apoptosis or autophagy, however, determined that a rapid accumulation of late stage endosomes/lysosomes precedes membrane permeabilisation, mitochondrial membrane depolarisation and caspase independent cell death.
Ajuts:	Ministerio de Economía y Competitividad SAF2015-64123-P
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Apoptosis ; CNS cancer
Publicat a:	Scientific reports, Vol. 9 (2019) , art. 12891, ISSN 2045-2322

DOI: 10.1038/s41598-019-49013-3
PMID: 31501494

12 p, 2.3 MB

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