Cell Death Induced by Nanosecond Pulsed Electric Fields and its Dependence on Pulse Duration

Objective. To evaluate the effects of nanosecond pulsed electric fields (nsPEFs) with different pulse durations in cell vitality, apoptosis, and proliferation of TPC-1 cells, optimize pulse parameters and expand the application range of nsPEFs. Methods. The pulse duration of 0, 300 ns, 500 ns, and 900 ns is generated with nsPEF generator. CCK-8 was used to investigate the effect of nsPEFs on the viability of TPC-1 cells. Flow cytometry was used to evaluate the apoptosis of TPC-1 after pulse treatment. The effect of nsPEFs on the proliferation ability of TPC-1 cells was detected by 5-ethy-nyl-2 ′ -deoxyuridine. The morphological changes of TPC-1 cells after pulse treatment were observed by transmission electron microscopy. Results. NsPEFs with 900 ns pulse duration can significantly affect the viability of TPC-1 cells and inhibit the proliferation ability of TPC-1 cells. In addition, nsPEFs can also induce apoptosis of TPC-1 cells. Conclusion. NsPEFs with longer pulse duration can significantly affect the biological behavior of TPC-1 cells, such as cell viability and proliferation ability, and can also induce cell apoptosis, thereby inhibiting cell growth.

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Towards Solid Tumor Treatment by Nanosecond Pulsed Electric Fields

Technology in Cancer Research & Treatment ◽

10.1177/153303460900800406 ◽

2009 ◽

Vol 8 (4) ◽

pp. 289-306 ◽

Cited By ~ 38

Author(s):

Axel T. Esser ◽

Kyle C. Smith ◽

T. R. Gowrishankar ◽

James C. Weaver

Keyword(s):

Cell Death ◽

Electric Field ◽

Spatial Scale ◽

Electric Fields ◽

Solid Tumor ◽

Irreversible Electroporation ◽

Pulsed Electric Fields ◽

Underlying Mechanism ◽

Tumor Ablation ◽

Nanosecond Pulsed Electric Fields

Local and drug-free solid tumor ablation by large nanosecond pulsed electric fields leads to supra-electroporation of all cellular membranes and has been observed to trigger nonthermal cell death by apoptosis. To establish pore-based effects as the underlying mechanism inducing apoptosis, we use a multicellular system model (spatial scale 100 μm) that has irregularly shaped liver cells and a multiscale liver tissue model (spatial scale 200 mm). Pore histograms for the multicellular model demonstrate the presence of only nanometer-sized pores due to nanosecond electric field pulses. The number of pores in the plasma membrane is such that the average tissue conductance during nanosecond electric field pulses is even higher than for longer irreversible electroporation pulses. It is shown, however, that these nanometer-sized pores, although numerous, only significantly change the permeability of the cellular membranes to small ions, but not to larger molecules. Tumor ablation by nanosecond pulsed electric fields causes small to moderate temperature increases. Thus, the underlying mechanism(s) that trigger cell death by apoptosis must be non-thermal electrical interactions, presumably leading to different ionic and molecular transport than for much longer irreversible electroporation pulses.

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Different involvement of extracellular calcium in two modes of cell death induced by nanosecond pulsed electric fields

Archives of Biochemistry and Biophysics ◽

10.1016/j.abb.2014.05.020 ◽

2014 ◽

Vol 555-556 ◽

pp. 47-54 ◽

Cited By ~ 35

Author(s):

Keiko Morotomi-Yano ◽

Hidenori Akiyama ◽

Ken-ichi Yano

Keyword(s):

Cell Death ◽

Electric Fields ◽

Pulsed Electric Fields ◽

Extracellular Calcium ◽

Nanosecond Pulsed Electric Fields

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Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied by Immunogenic Cell Death in Murine Models of Lymphoma and Colorectal Cancer

Cancers ◽

10.3390/cancers11122034 ◽

2019 ◽

Vol 11 (12) ◽

pp. 2034 ◽

Cited By ~ 4

Author(s):

Alessandra Rossi ◽

Olga N. Pakhomova ◽

Peter A. Mollica ◽

Maura Casciola ◽

Uma Mangalanathan ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Cell Death ◽

Er Stress ◽

Cell Lines ◽

Electric Fields ◽

Pulsed Electric Fields ◽

Immunogenic Cell Death ◽

Cancer Cell Death ◽

Cell Plasma ◽

Nanosecond Pulsed Electric Fields

Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of immunogenic cell death (ICD) rely on endoplasmic reticulum (ER) stress for the trafficking of danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric fields (nsPEF), an emerging new modality for tumor ablation, cause the activation of the ER-resident stress sensor PERK in both CT-26 colon carcinoma and EL-4 lymphoma cells. PERK activation correlates with sustained CRT exposure on the cell plasma membrane and apoptosis induction in both nsPEF-treated cell lines. Our results show that, in CT-26 cells, the activity of caspase-3/7 was increased fourteen-fold as compared with four-fold in EL-4 cells. Moreover, while nsPEF treatments induced the release of the ICD hallmark HMGB1 in both cell lines, extracellular ATP was detected only in CT-26. Finally, in vaccination assays, CT-26 cells treated with nsPEF or doxorubicin equally impaired the growth of tumors at challenge sites eliciting a protective anticancer immune response in 78% and 80% of the animals, respectively. As compared to CT-26, both nsPEF- and mitoxantrone-treated EL-4 cells had a less pronounced effect and protected 50% and 20% of the animals, respectively. These results support our conclusion that nsPEF induce ER stress, accompanied by bona fide ICD.

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