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Induction of Cell Death Mechanisms and Apoptosis by Nanosecond Pulsed Electric Fields (nsPEFs)
Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, IRP2, Norfolk, Virginia, 23508, USA
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; in revised form: 5 February 2013 / Accepted: 21 February 2013 / Published: 6 March 2013
(This article belongs to the Special Issue Apoptosis
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
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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.
Beebe SJ, Sain NM, Ren W. Induction of Cell Death Mechanisms and Apoptosis by Nanosecond Pulsed Electric Fields (nsPEFs). Cells. 2013; 2(1):136-162.
Beebe, Stephen J.; Sain, Nova M.; Ren, Wei. 2013. "Induction of Cell Death Mechanisms and Apoptosis by Nanosecond Pulsed Electric Fields (nsPEFs)." Cells 2, no. 1: 136-162.