Response of neuroblastoma cells to RF currents as a function of the signal frequency

• Published in: BMC cancer Vol. 19; no. 1; p. 889
• Main Authors: Hernández-Bule, María Luisa, Medel, Enrique, Colastra, Clara, Roldán, Raquel, Úbeda, Alejandro
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05-09-2019; BioMed Central; BMC
• Subjects: Alzheimer's disease; Apoptosis; Apoptosis - radiation effects; BAX protein; bcl-2-Associated X Protein - metabolism; Cancer; Cancer research; Cancer therapies; Capacitive-resistive electric transfer; Care and treatment; Caspase; Caspase 3 - metabolism; Caspase-3; Cell activation; Cell cycle; Cell Cycle Checkpoints - radiation effects; Cell death; Cell differentiation; Cell Line, Tumor; Cell proliferation; Cell Proliferation - radiation effects; Cell Survival - radiation effects; Cell viability; Cyclin D1; Cyclin D1 - metabolism; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Cytostasis; Electric currents; Electrothermal therapy; Epidermal growth factors; ErbB Receptors - metabolism; Fever; Flavonoids - pharmacology; Flow cytometry; Fluorescent antibody technique; Humans; Hyperthermia; Immunofluorescence; Kinases; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - radiation effects; NB69; Neural Crest - radiation effects; Neuroblastoma; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neuroblastoma - radiotherapy; Neuroblastoma cells; Oncology; p53 Protein; Proteins; Pulsed Radiofrequency Treatment - methods; Regeneration; Risk factors; Signal Transduction - radiation effects; Statistical analysis; Subthermal; Tumor proteins; Tumor Suppressor Protein p53 - metabolism; United States > US; Spain; NB69; Cytostasis; Electric currents; Electrothermal therapy; Subthermal; Apoptosis; Capacitive-resistive electric transfer
• DOI: 10.1186/s12885-019-6090-6
• EISSN: 1471-2407

Capacitive-resistive electric transfer (CRET) is a non-invasive therapeutic strategy that applies radiofrequency electric currents within the 400-600 kHz range to tissue repair and regeneration. Previous studies by our group have shown that 48 h of intermittent exposure to a 570 kHz CRET signal at a subthermal density of 50 μA/mm
causes significant changes in the expression and activation of cell cycle control proteins, leading to cycle arrest in human cancer cell cultures. The present study investigates the relevance of the signal frequency in the response of the human neuroblastoma cell line NB69 to subthermal electric treatment with four different signal frequency currents within the 350-650 kHz range.
Trypan blue assay, flow cytometry, immunofluorescence and immunoblot were used to study the effects of subthermal CRET currents on cell viability, cell cycle progression and the expression of several marker proteins involved in NB69 cell death and proliferation.
The results reveal that among the frequencies tested, only a 448 kHz signal elicited both proapoptotic and antiproliferative, statistically significant responses. The apoptotic effect would be due, at least in part, to significant changes induced by the 448 kHz signal in the expression of p53, Bax and caspase-3. The cytostatic response was preceded by alterations in the kinetics of the cell cycle and in the expression of proteins p-ERK1/2, cyclin D1 and p27, which is consistent with a potential involvement of the EGF receptor in electrically induced changes in the ERK1/2 pathway. This receives additional support from results indicating that the proapototic and antiproliferative responses to CRET can be transiently blocked when the electric stimulus is applied in the presence of PD98059, a chemical inhibitor of the ERK1/2 pathway.
The understanding of the mechanisms underlying the ability of slowing down cancer cell growth through electrically-induced changes in the expression of proteins involved in the control of cell proliferation and apoptosis might afford new insights in the field of oncology.