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Cells 2013, 2(1), 136-162; doi:10.3390/cells2010136
Review

Induction of Cell Death Mechanisms and Apoptosis by Nanosecond Pulsed Electric Fields (nsPEFs)

1,* , 1
 and
2
1 Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, IRP2, Norfolk, Virginia, 23508, USA 2 Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, Chinese Academy of Sciences, 1 Beichen West Road, Beijing 100101, China
* Author to whom correspondence should be addressed.
Received: 24 December 2012 / Revised: 5 February 2013 / Accepted: 21 February 2013 / Published: 6 March 2013
(This article belongs to the Special Issue Apoptosis)
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Abstract

Pulse power technology using nanosecond pulsed electric fields (nsPEFs) offers a new stimulus to modulate cell functions or induce cell death for cancer cell ablation. New data and a literature review demonstrate fundamental and basic cellular mechanisms when nsPEFs interact with cellular targets. NsPEFs supra-electroporate cells creating large numbers of nanopores in all cell membranes. While nsPEFs have multiple cellular targets, these studies show that nsPEF-induced dissipation of ΔΨm closely parallels deterioration in cell viability. Increases in intracellular Ca2+ alone were not sufficient for cell death; however, cell death depended of the presence of Ca2+. When both events occur, cell death ensues. Further, direct evidence supports the hypothesis that pulse rise-fall times or high frequency components of nsPEFs are important for decreasing ΔΨm and cell viability. Evidence indicates in Jurkat cells that cytochrome c release from mitochondria is caspase-independent indicating an absence of extrinsic apoptosis and that cell death can be caspase-dependent and –independent. The Ca2+ dependence of nsPEF-induced dissipation of ΔΨm suggests that nanoporation of inner mitochondria membranes is less likely and effects on a Ca2+-dependent protein(s) or the membrane in which it is embedded are more likely a target for nsPEF-induced cell death. The mitochondria permeability transition pore (mPTP) complex is a likely candidate. Data demonstrate that nsPEFs can bypass cancer mutations that evade apoptosis through mechanisms at either the DISC or the apoptosome.
Keywords: apoptosis; caspase-dependent; caspase-independent; Jurkat clones; APAF-1; FADD; N1-S1 hepatocellular carcinoma cells; Ca2+ mobilization; mitochondria membrane potential; mitochondria permeability transition pore; cytochrome c; electroporation; nanopores  3-10 apoptosis; caspase-dependent; caspase-independent; Jurkat clones; APAF-1; FADD; N1-S1 hepatocellular carcinoma cells; Ca2+ mobilization; mitochondria membrane potential; mitochondria permeability transition pore; cytochrome c; electroporation; nanopores  3-10
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Beebe, S.J.; Sain, N.M.; Ren, W. Induction of Cell Death Mechanisms and Apoptosis by Nanosecond Pulsed Electric Fields (nsPEFs). Cells 2013, 2, 136-162.

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