Cold Atmospheric Plasma induces accumulation of lysosomes and caspase-independent cell death in U373MG glioblastoma multiforme cells

Gillian E. Conway, Zhonglei He, Ana Lacramioara Hutanu, George Paul Cribaro, Eline Manaloto, Alan Casey, Damien Traynor, Vladimir Milosavljevic, Orla Howe, Carlos Barcia, James T. Murray, Patrick J. Cullen, James F. Curtin

Research output: Contribution to journalArticleResearch

6 Citations (Scopus)

Abstract

© 2019, The Author(s). 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.
Original languageEnglish
Article number12891
Pages (from-to)12891
Number of pages12
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 9 Sep 2019

Keywords

  • 3-METHYLADENINE
  • ADJUVANT TEMOZOLOMIDE
  • APOPTOSIS
  • AUTOPHAGY
  • MEMBRANE PERMEABILIZATION
  • MOLECULAR-MECHANISMS
  • NOMENCLATURE COMMITTEE
  • OXIDATIVE STRESS
  • RADIOTHERAPY
  • RECOMMENDATIONS

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