Related Experiment Video
Updated: May 9, 2026
Monitoring Electroporation-Induced Changes in Action Potential Generation in Genetically Engineered Tet-On Spiking HEK cells
Published on: September 6, 2024
Nanosecond pulsed electric fields induce poly(ADP-ribose) formation and non-apoptotic cell death in HeLa S3 cells
Keiko Morotomi-Yano1, Hidenori Akiyama, Ken-ichi Yano
1Institute of Pulsed Power Science, Kumamoto University, Kumamoto 860-8555, Japan.
Abstract:
Nanosecond pulsed electric fields (nsPEFs) have recently gained attention as effective cancer therapy owing to their potency for cell death induction. Previous studies have shown that apoptosis is a predominant mode of nsPEF-induced cell death in several cell lines, such as Jurkat cells. In this study, we analyzed molecular mechanisms for cell death induced by nsPEFs. When nsPEFs were applied to Jurkat cells, apoptosis was readily induced. Next, we used HeLa S3 cells and analyzed apoptotic events. Contrary to our expectation, nsPEF-exposed HeLa S3 cells exhibited no molecular signs of apoptosis execution. Instead, nsPEFs induced the formation of poly(ADP-ribose) (PAR), a hallmark of necrosis. PAR formation occurred concurrently with a decrease in cell viability, supporting implications of nsPEF-induced PAR formation for cell death. Necrotic PAR formation is known to be catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1), and PARP-1 in apoptotic cells is inactivated by caspase-mediated proteolysis. Consistently, we observed intact and cleaved forms of PARP-1 in nsPEF-exposed and UV-irradiated cells, respectively. Taken together, nsPEFs induce two distinct modes of cell death in a cell type-specific manner, and HeLa S3 cells show PAR-associated non-apoptotic cell death in response to nsPEFs.
Insights
Nanosecond pulsed electric fields (nsPEFs) induce distinct cell death pathways. While Jurkat cells undergo apoptosis, HeLa S3 cells exhibit PAR-associated necrosis, revealing cell-type-specific responses to nsPEFs.
Area of Science:
- Biophysics
- Cell Biology
- Cancer Research
Background:
- Nanosecond pulsed electric fields (nsPEFs) are emerging as a promising cancer therapy due to their cell death-inducing capabilities.
- Previous research indicated apoptosis as the primary cell death mechanism in response to nsPEFs in various cell lines, including Jurkat cells.
Purpose of the Study:
- To investigate the molecular mechanisms underlying nsPEF-induced cell death.
- To determine if nsPEFs trigger similar cell death pathways across different cell types.
Main Methods:
- Exposure of Jurkat and HeLa S3 cells to nsPEFs.
- Analysis of molecular markers for apoptosis and necrosis.
- Assessment of poly(ADP-ribose) (PAR) formation and poly(ADP-ribose) polymerase-1 (PARP-1) activity.
- Comparison with UV-irradiation-induced apoptosis.
Main Results:
- Jurkat cells readily underwent apoptosis upon nsPEF exposure.
- HeLa S3 cells did not show molecular signs of apoptosis but exhibited significant PAR formation, a marker of necrosis.
- PAR formation in HeLa S3 cells correlated with decreased cell viability.
- PARP-1 remained intact in nsPEF-treated HeLa S3 cells, unlike the cleaved form observed in UV-irradiated apoptotic cells.
Conclusions:
- nsPEFs induce cell death through distinct mechanisms in a cell type-specific manner.
- HeLa S3 cells undergo non-apoptotic, PAR-associated cell death in response to nsPEFs.
- This study highlights the differential cellular responses to nsPEF treatment, impacting potential therapeutic applications.
