Selective susceptibility to nanosecond pulsed electric field (nsPEF) across different human cell types

Tumor ablation by nanosecond pulsed electric fields (nsPEF) is an emerging therapeutic modality. We compared nsPEF cytotoxicity for human cell lines of cancerous (IMR-32, Hep G2, HT-1080, and HPAF-II) and non-cancerous origin (BJ and MRC-5) under strictly controlled and identical conditions. Adheren...

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Published in:Cellular and molecular life sciences : CMLS 2017-05, Vol.74 (9), p.1741-1754
Main Authors: Gianulis, Elena C., Labib, Chantelle, Saulis, Gintautas, Novickij, Vitalij, Pakhomova, Olga N., Pakhomov, Andrei G.
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cancer
Cell Biology
Cell Death
Cell Line
Cell Membrane - metabolism
Cell Membrane Permeability
Cell morphology
Cell Nucleus - metabolism
Cell Proliferation
Cell Shape
Cell Size
Cell Survival
Cytotoxicity
Electric fields
Electricity
Electroporation - methods
Humans
Life Sciences
Metabolism
Original Article
Time Factors
Tumors
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Summary:Tumor ablation by nanosecond pulsed electric fields (nsPEF) is an emerging therapeutic modality. We compared nsPEF cytotoxicity for human cell lines of cancerous (IMR-32, Hep G2, HT-1080, and HPAF-II) and non-cancerous origin (BJ and MRC-5) under strictly controlled and identical conditions. Adherent cells were uniformly treated by 300-ns PEF (0–2000 pulses, 1.8 kV/cm, 50 Hz) on indium tin oxide-covered glass coverslips, using the same media and serum. Cell survival plotted against the number of pulses displayed three distinct regions (initial resistivity, logarithmic survival decline, and residual resistivity) for all tested cell types, but with differences in LD 50 spanning as much as nearly 80-fold. The non-cancerous cells were less sensitive than IMR-32 neuroblastoma cells but more vulnerable than the other cancers tested. The cytotoxic efficiency showed no apparent correlation with cell or nuclear size, cell morphology, metabolism level, or the extent of membrane disruption by nsPEF. Increasing pulse duration to 9 µs (0.75 kV/cm, 5 Hz) produced a different selectivity pattern, suggesting that manipulation of PEF parameters can, at least for certain cancers, overcome their resistance to nsPEF ablation. Identifying mechanisms and cell markers of differential nsPEF susceptibility will critically contribute to the proper choice and outcome of nsPEF ablation therapies.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-016-2434-4