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Molecular Mechanisms Underlying Antiproliferative and Differentiating Responses of Hepatocarcinoma Cells to Subthermal Electric Stimulation

Capacitive Resistive Electric Transfer (CRET) therapy applies currents of 0.4–0.6 MHz to treatment of inflammatory and musculoskeletal injuries. Previous studies have shown that intermittent exposure to CRET currents at subthermal doses exert cytotoxic or antiproliferative effects in human neuroblas...

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Autores principales: Hernández-Bule, María Luisa, Trillo, María Ángeles, Úbeda, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885594/
https://www.ncbi.nlm.nih.gov/pubmed/24416255
http://dx.doi.org/10.1371/journal.pone.0084636
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author Hernández-Bule, María Luisa
Trillo, María Ángeles
Úbeda, Alejandro
author_facet Hernández-Bule, María Luisa
Trillo, María Ángeles
Úbeda, Alejandro
author_sort Hernández-Bule, María Luisa
collection PubMed
description Capacitive Resistive Electric Transfer (CRET) therapy applies currents of 0.4–0.6 MHz to treatment of inflammatory and musculoskeletal injuries. Previous studies have shown that intermittent exposure to CRET currents at subthermal doses exert cytotoxic or antiproliferative effects in human neuroblastoma or hepatocarcinoma cells, respectively. It has been proposed that such effects would be mediated by cell cycle arrest and by changes in the expression of cyclins and cyclin-dependent kinase inhibitors. The present work focuses on the study of the molecular mechanisms involved in CRET-induced cytostasis and investigates the possibility that the cellular response to the treatment extends to other phenomena, including induction of apoptosis and/or of changes in the differentiation stage of hepatocarcinoma cells. The obtained results show that the reported antiproliferative action of intermittent stimulation (5 m On/4 h Off) with 0.57 MHz, sine wave signal at a current density of 50 µA/mm(2), could be mediated by significant increase of the apoptotic rate as well as significant changes in the expression of proteins p53 and Bcl-2. The results also revealed a significantly decreased expression of alpha-fetoprotein in the treated samples, which, together with an increased concentration of albumin released into the medium by the stimulated cells, can be interpreted as evidence of a transient cytodifferentiating response elicited by the current. The fact that this type of electrical stimulation is capable of promoting both, differentiation and cell cycle arrest in human cancer cells, is of potential interest for a possible extension of the applications of CRET therapy towards the field of oncology.
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spelling pubmed-38855942014-01-10 Molecular Mechanisms Underlying Antiproliferative and Differentiating Responses of Hepatocarcinoma Cells to Subthermal Electric Stimulation Hernández-Bule, María Luisa Trillo, María Ángeles Úbeda, Alejandro PLoS One Research Article Capacitive Resistive Electric Transfer (CRET) therapy applies currents of 0.4–0.6 MHz to treatment of inflammatory and musculoskeletal injuries. Previous studies have shown that intermittent exposure to CRET currents at subthermal doses exert cytotoxic or antiproliferative effects in human neuroblastoma or hepatocarcinoma cells, respectively. It has been proposed that such effects would be mediated by cell cycle arrest and by changes in the expression of cyclins and cyclin-dependent kinase inhibitors. The present work focuses on the study of the molecular mechanisms involved in CRET-induced cytostasis and investigates the possibility that the cellular response to the treatment extends to other phenomena, including induction of apoptosis and/or of changes in the differentiation stage of hepatocarcinoma cells. The obtained results show that the reported antiproliferative action of intermittent stimulation (5 m On/4 h Off) with 0.57 MHz, sine wave signal at a current density of 50 µA/mm(2), could be mediated by significant increase of the apoptotic rate as well as significant changes in the expression of proteins p53 and Bcl-2. The results also revealed a significantly decreased expression of alpha-fetoprotein in the treated samples, which, together with an increased concentration of albumin released into the medium by the stimulated cells, can be interpreted as evidence of a transient cytodifferentiating response elicited by the current. The fact that this type of electrical stimulation is capable of promoting both, differentiation and cell cycle arrest in human cancer cells, is of potential interest for a possible extension of the applications of CRET therapy towards the field of oncology. Public Library of Science 2014-01-08 /pmc/articles/PMC3885594/ /pubmed/24416255 http://dx.doi.org/10.1371/journal.pone.0084636 Text en © 2014 Hernández-Bule et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hernández-Bule, María Luisa
Trillo, María Ángeles
Úbeda, Alejandro
Molecular Mechanisms Underlying Antiproliferative and Differentiating Responses of Hepatocarcinoma Cells to Subthermal Electric Stimulation
title Molecular Mechanisms Underlying Antiproliferative and Differentiating Responses of Hepatocarcinoma Cells to Subthermal Electric Stimulation
title_full Molecular Mechanisms Underlying Antiproliferative and Differentiating Responses of Hepatocarcinoma Cells to Subthermal Electric Stimulation
title_fullStr Molecular Mechanisms Underlying Antiproliferative and Differentiating Responses of Hepatocarcinoma Cells to Subthermal Electric Stimulation
title_full_unstemmed Molecular Mechanisms Underlying Antiproliferative and Differentiating Responses of Hepatocarcinoma Cells to Subthermal Electric Stimulation
title_short Molecular Mechanisms Underlying Antiproliferative and Differentiating Responses of Hepatocarcinoma Cells to Subthermal Electric Stimulation
title_sort molecular mechanisms underlying antiproliferative and differentiating responses of hepatocarcinoma cells to subthermal electric stimulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885594/
https://www.ncbi.nlm.nih.gov/pubmed/24416255
http://dx.doi.org/10.1371/journal.pone.0084636
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