Response of neuroblastoma cells to RF currents as a function of the signal frequency
Abstract Background 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 ...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-09-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12885-019-6090-6 |
| _version_ | 1828446434429501440 |
|---|---|
| author | María Luisa Hernández-Bule Enrique Medel Clara Colastra Raquel Roldán Alejandro Úbeda |
| author_facet | María Luisa Hernández-Bule Enrique Medel Clara Colastra Raquel Roldán Alejandro Úbeda |
| author_sort | María Luisa Hernández-Bule |
| collection | DOAJ |
| description | Abstract Background 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/mm2 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. Methods 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. Results 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. Conclusion 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. |
| first_indexed | 2024-12-10T22:12:21Z |
| format | Article |
| id | doaj.art-fb70e1d72e12409784791ecd8f3106fc |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-10T22:12:21Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-fb70e1d72e12409784791ecd8f3106fc2022-12-22T01:31:35ZengBMCBMC Cancer1471-24072019-09-0119111410.1186/s12885-019-6090-6Response of neuroblastoma cells to RF currents as a function of the signal frequencyMaría Luisa Hernández-Bule0Enrique Medel1Clara Colastra2Raquel Roldán3Alejandro Úbeda4BEM-Research Service, Ramón y Cajal University Hospital – IRYCISBEM-Research Service, Ramón y Cajal University Hospital – IRYCISBEM-Research Service, Ramón y Cajal University Hospital – IRYCISBEM-Research Service, Ramón y Cajal University Hospital – IRYCISBEM-Research Service, Ramón y Cajal University Hospital – IRYCISAbstract Background 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/mm2 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. Methods 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. Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s12885-019-6090-6Electric currentsNB69Capacitive-resistive electric transferElectrothermal therapySubthermalCytostasis |
| spellingShingle | María Luisa Hernández-Bule Enrique Medel Clara Colastra Raquel Roldán Alejandro Úbeda Response of neuroblastoma cells to RF currents as a function of the signal frequency BMC Cancer Electric currents NB69 Capacitive-resistive electric transfer Electrothermal therapy Subthermal Cytostasis |
| title | Response of neuroblastoma cells to RF currents as a function of the signal frequency |
| title_full | Response of neuroblastoma cells to RF currents as a function of the signal frequency |
| title_fullStr | Response of neuroblastoma cells to RF currents as a function of the signal frequency |
| title_full_unstemmed | Response of neuroblastoma cells to RF currents as a function of the signal frequency |
| title_short | Response of neuroblastoma cells to RF currents as a function of the signal frequency |
| title_sort | response of neuroblastoma cells to rf currents as a function of the signal frequency |
| topic | Electric currents NB69 Capacitive-resistive electric transfer Electrothermal therapy Subthermal Cytostasis |
| url | http://link.springer.com/article/10.1186/s12885-019-6090-6 |
| work_keys_str_mv | AT marialuisahernandezbule responseofneuroblastomacellstorfcurrentsasafunctionofthesignalfrequency AT enriquemedel responseofneuroblastomacellstorfcurrentsasafunctionofthesignalfrequency AT claracolastra responseofneuroblastomacellstorfcurrentsasafunctionofthesignalfrequency AT raquelroldan responseofneuroblastomacellstorfcurrentsasafunctionofthesignalfrequency AT alejandroubeda responseofneuroblastomacellstorfcurrentsasafunctionofthesignalfrequency |