title: Selective susceptibility to nanosecond pulsed electric field (nsPEF) across different human cell types.
abstract: 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 LD50spanning 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.
authors.affiliation: Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, Suite 300, Norfolk, VA, 23508, USA. egianulis@odu.edu.
authors.forename: Elena C
authors.identifier: 0000-0001-5490-1822
authors.initials: EC
authors.lastname: Gianulis
authors.affiliation: Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, Suite 300, Norfolk, VA, 23508, USA.
authors.forename: Chantelle
authors.initials: C
authors.lastname: Labib
authors.affiliation: Department of Biology, Faculty of Natural Sciences, Vytautas Magnus University, Kaunas, Lithuania.
authors.forename: Gintautas
authors.initials: G
authors.lastname: Saulis
authors.affiliation: Magnetic Field Institute, Vilnius Gediminas Technical University, Vilnius, Lithuania.
authors.forename: Vitalij
authors.initials: V
authors.lastname: Novickij
authors.affiliation: Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, Suite 300, Norfolk, VA, 23508, USA.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Pakhomova
authors.affiliation: Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, Suite 300, Norfolk, VA, 23508, USA.
authors.forename: Andrei G
authors.initials: AG
authors.lastname: Pakhomov
mesh_terms: D016923:Cell Death; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D048430:Cell Shape; D048429:Cell Size; D002470:Cell Survival; D004560:Electricity; D018274:Electroporation / Q000379:methods*; D006801:Humans; D013997:Time Factors
keywords: Cancer ablation; Cytotoxicity; Electroporation; Microsecond electric pulses; Nanosecond electric pulses