Calculated plasma membrane voltage induced by applying electric pulses using capacitive coupling

Robinson, Vance S.; Garner, Allen L.; Loveless, Amanda M.; Neculaes, V.B.

doi:10.1088/2057-1976/aa630a

Cited by 12 publications

(8 citation statements)

References 65 publications

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“…There have been recent studies of PEF using indirect contact of electrodes demonstrating the calculation of electric field effect and the induction of biological effects. 27 – 29 Nevertheless, the electric fields of conducting these experiments are at high intensities (>1,000 V/cm) and near the verge of electric breakdown, which can be a danger of causing electric current to flow through the body. This paper presents the first demonstration of a combination of low-dose curcumin and non-invasive low intensity PEF with contactless electrodes in the cancer treatment of PANC-1 cells.…”

Section: Introductionmentioning

confidence: 99%

Enhanced anticancer effects of low-dose curcumin with non-invasive pulsed electric field on PANC-1 cells

Lin

Hsieh

et al. 2018

OTT

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BackgroundPulsed electric field (PEF) has been considered as a cell permeability enhancing agent for cancer treatment. Nevertheless, application of PEF for conventional electrochemo-therapy is usually at high intensity, and contact or even invasive electrodes are typically used, which may cause unwanted side effects. In this study, a non-invasive way of applying low intensity, non-contact PEF was adopted to study its combination effect with herb, curcumin, against pancreatic cancer cells and the mechanism involved.MethodsThe pancreatic cancer PANC-1 cells were treated with curcumin and PEF alone or in combination, and MTT assay was used to determine the viability of PANC-1 cells. Apoptosis and uptake of curcumin were analyzed by microscopy and flow cytometry. Western blot was further performed to evaluate the expression of apoptotic proteins.ResultsOur results demonstrated that PEF synergized with curcumin to inhibit the proliferation of PANC-1 cells in a field strength- and dose-dependent manner and caused apoptotic death of PANC-1 cells. The apoptotic induction of combination treatment was characterized by an increase in Bax/Bcl-2 ratio, and cleavage of caspase-8, -9, and -3. Moreover, the increase of curcumin uptake via electro-endocytosis was clearly observed in the cells following the exposure of PEF.ConclusionWe show for the first time that a non-contact approach using low intensity electric field in a pulsed waveform could enhance the anticancer effect of low-dose curcumin on PANC-1 cells through triggering both extrinsic and intrinsic pathways. The findings highlight the potential of this alternative treatment, non-invasive electric field and curcumin, to increase therapeutic efficacy with minimum cytotoxicity and side effects, which may provide a new aspect of cancer treatment in combination of PEF and other anticancer agents.

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Section: Introductionmentioning

confidence: 99%

Enhanced anticancer effects of low-dose curcumin with non-invasive pulsed electric field on PANC-1 cells

Lin

Hsieh

et al. 2018

OTT

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“…Furthermore, the high-frequency component of PEF was proposed to penetrate through cytomembrane and to affect intermembrane organelles, such as mitochondria and nucleus [ 19 , 20 , 45 – 47 ]. Recent calculations have also shown a little change of membrane voltage could be induced by non-invasive high strength PEF (> 1000 V/cm) [ 27 ], but the bio-effects induced by non-invasive low strength PEF alone or combined with natural agents remain unknown. Here, we suggested that the synergistic reactions triggered by combination treatment could intensify the disturbance of mitochondria and enhance the depolarization of MMP due to the application of PEF.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the electroporation by means of direct contact of the cells with electrodes [ 19 , 22 ] may result in undesirable leakage current and could be dangerous for therapy [ 23 , 24 ]. Recently, high intensity PEF exposure using indirect contact with electrodes was calculated and shown to induce biological effects [ 25 – 27 ]; nevertheless, the electric intensities employed in these studies (> 1000 V/cm) are too high and on the verge of dielectric breakdown, which is hazardous if electric current travels through the body [ 28 ]. Hence, we first propose that anti-cancer treatment with non-invasive low strength pulsed electric field (PEF) would be more suitable for patients.…”

Section: Introductionmentioning

confidence: 99%

Application of non-invasive low strength pulsed electric field to EGCG treatment synergistically enhanced the inhibition effect on PANC-1 cells

Hsieh

Chen

et al. 2017

PLoS ONE

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Traditional therapies for pancreatic cancer are usually expensive and likely to cause side effects, and most patients have the risk of recurrence and suffering pain. Here, we investigated combination treatment of epigallocatechin-3-gallate (EGCG) and non-invasive low strength pulsed electric field (PEF) on the human pancreatic cell line PANC-1. Cells were cultured in various concentrations of EGCG and exposed to trains of PEF. The results showed that the low strength PEF alone or single treatment with low concentration of EGCG did not obviously affect the cell proliferation and migration in PANC-1. However, the EGCG-induced inhibitions of cell viability and migration ability in PANC-1 were dramatically enhanced by the further exposure of low strength PEF (60 V/cm). In particular, the same combination treatment caused less inhibition of cell viability in non-malignant HEK293 cells. We also found the combination treatment significantly decreased the ratio of Bcl-2/Bax protein and increased caspase activity in PANC-1 cells, resulting in the promotion of apoptotic responses, evidenced by chromatin condensation. The findings of the present study reveal the synergistic reactions in the combination treatment may severely disturb mitochondria, enhance the intrinsic pathway transduction, and effectively induce apoptosis; moreover, the migration and invasion of PANC-1 cancer cells were also significantly suppressed. Since normal cells are less sensitive to this combination treatment, and the non-invasive PEF could be modified to focus on a specific location, this treatment may serve as a promising method for anti-cancer therapy.

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“…There are two models of electrical stimulation: conductive coupling and capacitive coupling [18]. In our experimental design, we adopted capacitive coupling model to investigate the externally applied LIPEF in combination with anticancer agents on pancreatic cancer.…”

Section: Experimental Setup Of Lipefmentioning

confidence: 99%

Application of non-invasive low-intensity pulsed electric field with thermal cycling-hyperthermia for synergistically enhanced anticancer effect of chlorogenic acid on PANC-1 cells

Kuo

Lin

et al. 2020

PLoS ONE

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Most existing cancer treatments involve high-cost chemotherapy and radiotherapy, with major side effects, prompting effort to develop alternative treatment modalities. It was reported that the combination of thermal-cycling hyperthermia (TC-HT) and phenolic compound exhibited a moderate cytotoxic effect against human pancreatic cancer PANC-1 cells. In this study, we investigate the efficacy of triple combination in PANC-1 cancer cells by adopting low-intensity pulsed electric field (LIPEF) to couple with TC-HT and CGA (chlorogenic acid). The study finds that this triple combination can significantly impede the proliferation of PANC-1 cells, with only about 20% viable cells left after 24h, whereas being nontoxic to normal cells. The synergistic activity against the PANC-1 cells was achieved by inducing G2/M phase arrest and apoptosis, which were associated with up-regulation of p53 and coupled with increased expression of downstream proteins p21 and Bax. Further mechanism investigations revealed that the cytotoxic activity could be related to mitochondrial apoptosis, characterized by the reduced level of Bcl-2, mitochondrial dysfunction, and sequential activation of caspase-9 and PARP. Also, we found that the triple treatment led to the increase of intracellular reactive oxygen species (ROS) production. Notably, the triple treatment-induced cytotoxic effects and the elevated expression of p53 and p21 proteins as well as the increased Bax/Bcl-2 ratio, all could be alleviated by the ROS scavenger, N-acetyl-cysteine (NAC). These findings indicate that the combination of CGA, TC-HT, and LIPEF may be a promising modality for cancer treatment, as it can induce p53-dependent cell cycle arrest and apoptosis through accumulation of ROS in PANC-1 cells.

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Calculated plasma membrane voltage induced by applying electric pulses using capacitive coupling

Cited by 12 publications

References 65 publications

Enhanced anticancer effects of low-dose curcumin with non-invasive pulsed electric field on PANC-1 cells

Enhanced anticancer effects of low-dose curcumin with non-invasive pulsed electric field on PANC-1 cells

Application of non-invasive low strength pulsed electric field to EGCG treatment synergistically enhanced the inhibition effect on PANC-1 cells

Application of non-invasive low-intensity pulsed electric field with thermal cycling-hyperthermia for synergistically enhanced anticancer effect of chlorogenic acid on PANC-1 cells

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