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The cytotoxic synergy of nanosecond electric pulses and low temperature leads to apoptosis
- Source :
- Scientific Reports
- Publication Year :
- 2016
- Publisher :
- Nature Publishing Group, 2016.
-
Abstract
- Electroporation by nanosecond electric pulses (nsEP) is an emerging modality for tumor ablation. Here we show the efficient induction of apoptosis even by a non-toxic nsEP exposure when it is followed by a 30-min chilling on ice. This chilling itself had no impact on the survival of U-937 or HPAF-II cells, but caused more than 75% lethality in nsEP-treated cells (300 ns, 1.8-7 kV/cm, 50-700 pulses). The cell death was largely delayed by 5-23 hr and was accompanied by a 5-fold activation of caspase 3/7 (compared to nsEP without chilling) and more than 60% cleavage of poly-ADP ribose polymerase (compared to less than 5% in controls or after nsEP or chilling applied separately). When nsEP caused a transient permeabilization of 83% of cells to propidium iodide, cells placed at 37 °C resealed in 10 min, whereas 60% of cells placed on ice remained propidium-permeable even in 30 min. The delayed membrane resealing caused cell swelling, which could be blocked by an isosmotic addition of a pore-impermeable solute (sucrose). However, the block of swelling did not prevent the delayed cell death by apoptosis. The potent enhancement of nsEP cytotoxicity by subsequent non-damaging chilling may find applications in tumor ablation therapies.
- Subjects :
- 0301 basic medicine
Programmed cell death
Cell Membrane Permeability
Poly (ADP-Ribose) Polymerase-1
Apoptosis
Caspase 3
Biology
Article
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Line, Tumor
Humans
Cytotoxic T cell
Propidium iodide
Cytotoxicity
Cell Size
Caspase 7
Multidisciplinary
Electroporation
Cell Membrane
Cell biology
Cold Temperature
Enzyme Activation
030104 developmental biology
chemistry
Cell culture
030220 oncology & carcinogenesis
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....d9751a54c6677a076364f0499bfe187f
- Full Text :
- https://doi.org/10.1038/srep36835