Antagonistic Effects of a 50 Hz Magnetic Field and Melatonin in the Proliferation and Differentiation of Hepatocarcinoma Cells

Cid, María Antonia; Úbeda, Alejandro; Hernández-Bule, María Luisa; Martínez, María Antonia; Trillo, María Ángeles

doi:10.1159/000343338

Cited by 18 publications

(16 citation statements)

References 72 publications

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“…Specifically, AFP, which is synthesized by transformed hepatocytes with high-grade malignancy, is known to be present in HepG2 cells [22]. In fact, all cells in the images taken from our HepG2 cultures expressed AFP to a greater or lesser extent.…”

Section: Resultsmentioning

confidence: 81%

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

2014

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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/mm2, 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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Section: Resultsmentioning

confidence: 81%

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

2014

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“…Interestingly, the exposure to weak, extremely low frequency magnetic fields could also affect cancer progression. However, the cytoproliferative and dedifferentiating effects exerted by magnetic fields were prevented after 10 nM melatonin treatment in HepG2 cells [173]. …”

Section: Protective Effects Of Melatonin On Hepatocarcinomamentioning

confidence: 99%

Effects of Melatonin on Liver Injuries and Diseases

Zhang

Meng

et al. 2017

IJMS

102

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Liver injuries and diseases are serious health problems worldwide. Various factors, such as chemical pollutants, drugs, and alcohol, could induce liver injuries. Liver diseases involve a wide range of liver pathologies, including hepatic steatosis, fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocarcinoma. Despite all the studies performed up to now, therapy choices for liver injuries and diseases are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries and diseases remains a priority. Melatonin is a well-known natural antioxidant, and has many bioactivities. There are numerous studies investigating the effects of melatonin on liver injuries and diseases, and melatonin could regulate various molecular pathways, such as inflammation, proliferation, apoptosis, metastasis, and autophagy in different pathophysiological situations. Melatonin could be used for preventing and treating liver injuries and diseases. Herein, we conduct a review summarizing the potential roles of melatonin in liver injuries and diseases, paying special attention to the mechanisms of action.

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“…In order to identify and characterize the cellular processes involved in the potential proliferative effects of ELF MF, a number of studies have investigated the in vitro response to those fields when administered in combination with different chemical species including antioxidants like melatonin or tamoxifen (14)(15)(16)(17)(18)(19), or radical-inducing agents like menadione (20) and tumor promoters like DMBA (21).…”

Section: Introductionmentioning

confidence: 99%

Influence of a 50 Hz magnetic field and of all-trans‑retinol on the proliferation of human cancer cell lines

Trillo

2012

Int J Oncol

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Abstract. In vitro exposure to power frequency magnetic fields (MF) has been reported to influence cell proliferation and differentiation. However, the nature of the response of different human cancer cell types to these fields has not been sufficiently characterized. The present work investigates the response of two proliferating human cell lines of neuroblastoma (NB69) and hepatocarcinoma (HepG2) to a 42 h, intermittent treatment with a weak, 100 µT, 50 Hz MF, alone or in combination with 0.5 µM all-trans-retinol (ROL), a retinoid currently applied in oncostatic therapies. In each experimental replicate the cell samples were submitted to one of the following treatment combinations: MF+/ROL+, MF+/ ROL-, MF-/ROL+ or MF-/ROL-. The proliferative response was determined by cell counting (Trypan blue exclusion), BrdU incorporation and by spectrophotometric analysis of total protein and DNA content. The results show that when administered separately, the two treatments, MF and ROL, significantly enhanced cell proliferation in both cell lines. In NB69 simultaneous administration of MF and ROL induced an additive effect on cell proliferation, associated to increased DNA content. By contrast, in HepG2 the ROL-induced cell proliferation and increased protein content were partially blocked by simultaneous exposure to MF. Taken together, these data show that both agents, a weak MF and ROL at a low concentration, induce proliferative responses in the two assayed human cell lines. However, significant differences were observed between the responses of the two cellular species to the combined treatment with ROL and MF, indicating that the mechanisms underlying the cellular response to each of the two agents can mutually interact in a manner that is cell type-specific.

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Antagonistic Effects of a 50 Hz Magnetic Field and Melatonin in the Proliferation and Differentiation of Hepatocarcinoma Cells

Cited by 18 publications

References 72 publications

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

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

Effects of Melatonin on Liver Injuries and Diseases

Influence of a 50 Hz magnetic field and of all-trans‑retinol on the proliferation of human cancer cell lines

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