Irreversible electroporation and apoptosis in human liver cancer cells induced by nanosecond electric pulses

Abstract

The goal of this study was to assess the effect of nanosecond electric pulses on HepG2 human liver cancer cells. Electric pulses with a high strength of 10 kV/cm, duration of 500 ns and frequency of 1 Hz were applied to the cells. After delivery of electric pulses, apoptosis, intracellular calcium ion concentrations, transmembrane mitochondrial potentials, electropermeabilization and recovery from electropermeabilization in cells were investigated. The results showed that electric pulse treatment for 20 s and more could trigger apoptosis in cells. Real-time observation indicated an immediate increase in intracellular calcium ion concentration and a dramatic decrease in mitochondrial membrane potential in cells responding to electric pulses. In subsequent experiments, propidium iodide uptake in cells emerged after exposure to electric pulses, indicating electropermeabilization of the cell membrane. Furthermore, recovery from electropermeabilization was not observed even 4 h after the stimulation, demonstrating that irreversible electropermeabilization was induced by electric pulses. In conclusion, electric pulses with a high strength and nanosecond duration can damage cancer cells, accompanied by a series of intracellular changes, providing strong evidence for the application of electric pulses in cancer treatment.

Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma

“…Owing to its ultra-short duration and rise time, nsPEFs induce various biomedical effects that are clearly distinct from those of conventional electroporation. They have been reported to trigger various cellular responses, including phosphatidylserine translocation, cell membrane permeabilisation, and loss of mitochondrial membrane potential22232425. Besides, nsPEFs create little thermal effects when biological tissues or materials are treated2627.…”

Histological and Mathematical Analysis of the Irreversibly Electroporated Liver Tissue

“…The criterion of the ablation is that the local electric field strength exceeds a critical value. [23][24][25][26] Assuming the time-independent electrical conductivity of tissue, 8 this criterion results in a timeindependent ablation area. However, in an experiment, the ablated area increases as the time of electric shock increases, and this has been empirically modeled by a reduction in the critical electric field over time.…”

“…The highintensive electric energy produces irreversible structural changes in the cell membrane, which causes cells to undergo apoptotic pathways and consequently necrotic cell death. 7,8 This nonthermal mechanism of IRE is a big advantage, as compared to thermal ablation such as radiofrequency ablation, because the major blood vessel and nerve architecture as well as the extracellular matrix are preserved during IRE. [9][10][11][12][13] This enables IRE-induced lesions to be rapidly healed within 2 weeks after treatment.…”

High-frequency submicrosecond electroporator

“…[7,8] For larger molecules or non-reversible electroporation, the intensity of the electric field may be increased from several kV/cm to tens of kV/cm. [9] In each case, development of high-voltage generators (electroporators) which are capable of delivering adjustable energy pulses to the biological loads is required.…”