In vitro exposure to 0.57-MHz electric currents exerts cytostatic effects in HepG2 human hepatocarcinoma cells

Hernández-Bule, María Luisa; Trillo, María Ángeles; Cid, María Antonia; Leal, José M.; Úbeda, Alejandro

doi:10.3892/ijo.30.3.583

Cited by 19 publications

(65 citation statements)

References 27 publications

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“…It was found that the electrically induced hyperthermic stimuli decreased cellular proliferation, possibly due to blocking of the cell cycle in a fraction of the cell population (Hernández-Bule et al 2007). Correspondingly to this, it is speculated that cell proliferation of HSC-4 cells was inhibited by 0.25 mM Asc6Palm owing to cell cycle arrest, rather than lethal effects on treated cells.…”

Section: Discussionmentioning

confidence: 99%

“…CRet system is used for a non-invasive electro-thermal therapy, based on the application of electric currents in the frequency range of 0.45 MHz, which can produce the electric stimulus and thermal effects synergistically in tissues (Hernández-Bule et al 2007). Sub-confluent HSC-4 cells were seeded at 8,000 cells per well of a 24-well culture plate (Becton, Dickinson and Company, NJ, USA) in 500 lL MEM-10% FBS and incubated for 48 h at 37°C in a 95% humidified air and 5% CO 2 .…”

Section: Cell Culturementioning

confidence: 99%

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Anticancer effects of 6-o-palmitoyl-ascorbate combined with a capacitive-resistive electric transfer hyperthermic apparatus as compared with ascorbate in relation to ascorbyl radical generation

et al. 2011

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The aim of the present study is to determine the anti-proliferative activity of 6-o-palmitoyl-L-ascorbic acid (Asc6Palm) that is a lipophilic derivative of L-ascorbic acid (Asc), on human tongue squamous carcinoma HSC-4 cells by combined use of hyperthermia in comparison to Asc. Asc6Palm or Asc were administered to HSC-4 cells for 1 h, to which hyperthermia at 42°C was applied for initial 15 min. After further 1-72 h incubation at 37°C, cell proliferation was determined with Crystal Violet staining. Ascorbyl radical (AscR) in HSC-4 cell suspension was measured by electron spin resonance (ESR), and cell morphology was observed with scanning electron microscopy (SEM). At 37°C, 4 mM Asc or 0.35 mM Asc6Palm were enough to suppress proliferation of HSC-4 cells. By combined use of hyperthermia at 42°C, cell proliferation was decreased when compared to 37°C. After Asc of 4 mM was incubated with HSC-4 cell suspensions at 37°C or 42°C for 0-180 min, the signal intensity of ascorbyl radical (AscR) by ESR was not different regardless of the presence or absence of cells at 37°C, whereas AscR signal was enlarged in the presence of HSC-4 cells at 42°C. It was suggested that oxidation of Asc occurred rapidly in HSC-4 cells by hyperthermia, and thereby enhanced the anti-proliferative activity. By SEM observation, the surface of HSC-4 cells treated with Asc6Palm revealed distinct morphological changes. Thus, the combined regimen of Asc6Palm and hyperthermia is expected to exert a marked antitumor activity.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Anticancer effects of 6-o-palmitoyl-ascorbate combined with a capacitive-resistive electric transfer hyperthermic apparatus as compared with ascorbate in relation to ascorbyl radical generation

et al. 2011

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“…The 50 μA/mm 2 current density used in these in vitro experiments is within the range of thermal treatments applied to patients. However, in our experimental conditions such doses do not cause temperature increase of the cells due to the configuration of the exposure setup and to the electric properties to the culture medium (8). This represents a significant methodological advantage, allowing us to study the cellular response to the electric stimulus alone, without increasing the temperature of the medium, which could act as a confounding factor.…”

Section: Introductionmentioning

confidence: 99%

“…This represents a significant methodological advantage, allowing us to study the cellular response to the electric stimulus alone, without increasing the temperature of the medium, which could act as a confounding factor. We have reported that such treatment can induce statistically significant responses, at the cellular and molecular levels, in neuroblastoma (NB69) and hepatocarcinoma (HepG2) cell lines from human origin, when exposed during the exponential growth phase (8,17). In NB69 cells the electric stimulus caused increased rate of necrosis followed by decreased cell proliferation, this response being attributable to alterations in cell cycle progression (17).…”

Section: Introductionmentioning

confidence: 99%

“…This therapy has proved effective in restoring damaged tissues including muscle, tendon or vessels (8). Additionally, preliminary tests conducted in cancer patients suffering from glioblastoma multiforme have shown that CRet treatment induced necrosis and decreased tumor growth, which was interpreted as indicative of an oncostatic ability of the therapy (9,10).…”

Section: Introductionmentioning

confidence: 99%

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Cytostatic response of HepG2 to 0.57 MHz electric currents mediated by changes in cell cycle control proteins

Hernández-Bule

Cid²,

Trillo³

et al. 2010

Int J Oncol

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Abstract. The capacitive-resistive electric transfer (CRet) therapy is a non-invasive technique that applies electrical currents of 0.4-0.6 MHz to the treatment of musculoskeletal injuries. Although this therapy has proved effective in clinical studies, its interaction mechanisms at the cellular level still are insufficiently investigated. Results from previous studies have shown that the application of CRet currents at subthermal doses causes alterations in cell cycle progression and decreased proliferation in hepatocarcinoma (HepG2) and neuroblastoma (NB69) human cell lines. The aim of the present study was to investigate the antiproliferative response of HepG2 to CRet currents. The results showed that 24-h intermittent treatment with 50 μA/mm 2 current density induced in HepG2 statistically significant changes in expression and activation of cell cycle control proteins p27Kip1 and cyclins D1, A and B1. The chronology of these changes is coherent with that of the alterations reported in the cell cycle of HepG2 when exposed to the same electric treatment. We propose that the antiproliferative effect exerted by the electric stimulus would be primarily mediated by changes in the expression and activation of proteins intervening in cell cycle regulation, which are among the targets of emerging chemical therapies. The capability to arrest the cell cycle through electrically-induced changes in cell cycle control proteins might open new possibilities in the field of oncology.

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In vitro stimulation with radiofrequency currents promotes proliferation and migration in human keratinocytes and fibroblasts

Hernández-Bule

Toledano-Macías

Naranjo

et al. 2021

Electromagnetic Biology and Medicine

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Capacitive-resistive electric transfer (CRET) therapies have been proposed as strategies for regeneration of cutaneous tissue lesions. Previous studies by our group have shown that intermittent stimulation with 448 kHz CRET currents at subthermal densities promotes in vitro proliferation of human stem cells involved in tissue regeneration. The present study investigates the effects of the in vitro exposure to these radiofrequency (RF) currents on the proliferation and migration of keratinocytes and fibroblasts, the main cell types involved in skin regeneration. The effects of the electric stimulation on cell proliferation and migration were studied through XTT and wound closure assays, respectively. The CRET effects on the expression and location of proteins involved in proliferation and migration were assessed by immunoblot and immunofluorescence. The obtained results reveal that electrostimulation promotes proliferation and/or migration in keratinocytes and fibroblasts. These effects would be mediated by changes observed in the expression and location of intercellular adhesion proteins such as β-catenin and E-cadherin, of proteins involved in cell-to-substrate adhesion such as vinculin, p-FAK and the metalloproteinase MMP-9, and of other proteins that control both processes: MAP kinases p-p38, p-JUNK and p-ERK1/2. These responses could represent a mechanism underlying the promotion of normotrophic wound regeneration induced by CRET. Indeed, electric stimulation would favor completion of granulation tissue formation prior to the closure of the outer tissue layers, thus preventing abnormal wound cicatrization or chronification.

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In vitro exposure to 0.57-MHz electric currents exerts cytostatic effects in HepG2 human hepatocarcinoma cells

Cited by 19 publications

References 27 publications

Anticancer effects of 6-o-palmitoyl-ascorbate combined with a capacitive-resistive electric transfer hyperthermic apparatus as compared with ascorbate in relation to ascorbyl radical generation

Anticancer effects of 6-o-palmitoyl-ascorbate combined with a capacitive-resistive electric transfer hyperthermic apparatus as compared with ascorbate in relation to ascorbyl radical generation

Cytostatic response of HepG2 to 0.57 MHz electric currents mediated by changes in cell cycle control proteins

In vitro stimulation with radiofrequency currents promotes proliferation and migration in human keratinocytes and fibroblasts

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