Activation of autophagy in response to nanosecond pulsed electric field exposure

Ullery, Jody C.; Tarango, Melissa; Roth, Caleb C.; Ibey, Bennett L.

doi:10.1016/j.bbrc.2015.01.131

Cited by 28 publications

(26 citation statements)

References 24 publications

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“…Indeed, although autophagy was not investigated, our results show that ATP secretion correlates with IRE1 activation by nsPEF in CT26 cells. Moreover, nsPEF can induce autophagy, as shown by Ullery et al, in both human lymphoma U937 and Chinese Hamster Ovarian-K1 (CHO-K1) cells [96].…”

Section: Discussionmentioning

confidence: 87%

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

Rossi

Pakhomova

Mollica

et al. 2019

Cancers

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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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Section: Discussionmentioning

confidence: 87%

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

Rossi

Pakhomova

Mollica

et al. 2019

Cancers

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“…These morphological changes are closely associated with cell death and have been identified as markers of both apoptosis [8] , [16] or necrosis [8] , [16] . In addition to these phenomena, molecular/biochemical events such as the influx of calcium [17] , [18] , [19] , [20] , the activation of the inositol triphosphate (IP 3 ) pathway [21] , [22] , [23] , the creation of reactive oxygen species (ROS) [24] , [25] , [26] and the induction of autophagy [27] have also been reported as being associated with nsEP exposure.…”

Section: Introductionmentioning

confidence: 99%

Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress

Roth

Glickman

Martens³

et al. 2017

Biochemistry and Biophysics Reports

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BackgroundExposure of cells to very short (<1 µs) electric pulses in the megavolt/meter range have been shown to cause a multitude of effects, both physical and molecular in nature. Physically, nanosecond electrical pulses (nsEP) can cause disruption of the plasma membrane, cellular swelling, shrinking and blebbing. Molecularly, nsEP have been shown to activate signaling pathways, produce oxidative stress, stimulate hormone secretion and induce both apoptotic and necrotic death. We hypothesize that studying the genetic response of primary human dermal fibroblasts exposed to nsEP, will gain insight into the molecular mechanism(s) either activated directly by nsEP, or indirectly through electrophysiology interactions.MethodsMicroarray analysis in conjunction with quantitative real time polymerase chain reaction (qRT-PCR) was used to screen and validate genes selectively upregulated in response to nsEP exposure.ResultsExpression profiles of 486 genes were found to be significantly changed by nsEP exposure. 50% of the top 20 responding genes coded for proteins located in two distinct cellular locations, the plasma membrane and the nucleus. Further analysis of five of the top 20 upregulated genes indicated that the HDFa cells’ response to nsEP exposure included many elements of a mechanical stress response.ConclusionsWe found that several genes, some of which are mechanosensitive, were selectively upregulated due to nsEP exposure. This genetic response appears to be a primary response to the stimuli and not a secondary response to cellular swelling.General significanceThis work provides strong evidence that cells exposed to nsEP interpret the insult as a mechanical stress.

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“…In addition, previous studies have shown that nsPEF has extensive biological effects in colon cancer [26][27], ovarian cancer [28][29], oral cancer [30][31][32], pancreatic cancer [33], and brosarcoma [34]. In addition to inducing tumour cell apoptosis, nsPEF modulates tumour cell proliferation, invasion and metastasis, the tumour microenvironment, angiogenesis, and other tumour characteristics [35][36][37][38][39][40].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Nanosecond Pulsed Electric Field on Hepatic Veins—A Mid-Term Investigation

Dong¹,

Lu²,

Huang³

et al. 2020

Preprint

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Background: Nanosecond pulsed electric field (nsPEF) is a novel ablative technique for treating tumours of the liver, kidneys, and other organs. This study investigated the effect of nsPEF on hepatic veins of different diameters and evaluated the feasibility and safety of using nsPEF to ablate tissues in porcine livers.Methods: A total of 15 pigs were included in the study. B-mode ultrasonography was used to guide two-needle nsPEF electrodes inserted adjacent to the left, middle, and right hepatic veins. The animals were followed up at 1 hour and at 1, 3, 7, and 14 days post treatment. Results: During and after the procedure of nsPEF treatment, electrocardiographs (ECGs) detected no cardiovascular events, and B-mode ultrasonography found no hepatic venous thrombosis formation. Follow-up at 1 hour to 7 days post treatment revealed complete ablation of the perivascular tissue within the ablated area. There was no apparent structural damage to the hepatic veins of different diameters, but there appeared to be red blood cells and residual inflammatory cell infiltration in the subendothelial layer from 1 hour to 7 days post treatment. Follow-up blood biochemical tests showed transient damage to the liver and myocardial function, and immediate recovery, which is consistent with the pathological changes.Conclusion: NsPEF achieved complete liver tissue ablation while causing little damage to the hepatic veins. Thus, nsPEF could be used to ablate central tumour lesions that are located nearing the major hepatic veins, thereby avoiding some of the limitations of conventional surgical therapies and thermal ablations.

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Activation of autophagy in response to nanosecond pulsed electric field exposure

Cited by 28 publications

References 24 publications

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

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

Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress

The Effect of Nanosecond Pulsed Electric Field on Hepatic Veins—A Mid-Term Investigation

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