Effects of Fifty-Hertz Electromagnetic Fields on Granulocytic Differentiation of ATRA-Treated Acute Promyelocytic Leukemia NB4 Cells

Abstract

Background/Aims: Life on Earth is constantly exposed to electromagnetic fields (EMFs) and the effects induced by EMFs on biological systems have been extensively studied producing different and sometimes contradictory results. Extremely low-frequency electromagnetic fields (ELF-EMFs) have shown to play a role in regulating cell proliferation and differentiation, although how EMFs influence these processes remains unclear. Human acute promyelocytic leukemia (APL) cells are characterized by the arrest of differentiation at the promyelocytic stage due to epigenetic perturbations induced by PML/RARα fusion protein (Promyelocytic Leukemia protein - PML/Retinoic Acid Receptor alpha - RARα). Therapeutic administration of all-trans retinoic acid (ATRA) re-establishes the leukemogenic mechanism re-inducing the normal differentiation processes. Methods: We studied the effects of ELF-EMFs (50 Hz, 2 mT) on the ATRA-mediated granulocytic differentiation process of APL NB4 cells (a cell line established from the bone marrow of a patient affected by the acute promyelocytic leukemia) by monitoring cellular proliferation and morphology, nitrob lue tetrazolium (NBT) reduction and the expression of differentiation surface markers. Finally, we investigated mechanisms focusing on reactive oxygen species (ROS) generation and related molecular pathways. Results: ELF-EMF exposure decreases cellular proliferation potential and helps ATRA-treated NB4 cells to mature. Furthermore, the analysis of ROS production and the consequent extracellular signal regulated kinases (ERK1/2) phosphorylation suggest that a changed intracellular oxidative balance may influence the biological effects of ELF-EMFs. Conclusions: These results indicate that the exposure to ELF-EMF promotes ATRA-induced granulocytic differentiation of APL cells.

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

“…2020, 21, 2952 2 of 14 processes [9]. Further research has found that low-frequency magnetic fields (LF-MFs), namely, those with a frequency below 300 Hz, possess a variety of effects such as the regulation of immunity [10] and inflammation [11], suppression of angiogenesis [12], contribution to differentiation [13], and induced apoptosis [14]. Although many biological effects of magnetic fields have been reported, the mechanisms involved still remain unclear.Reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are one of the main causes of tumors and play an important role in the process of tumor progression, metastasis and apoptosis [15].…”

The effect of electromagnetic field on decreasing and increasing of the growth and proliferation rate of dermal fibroblast cell

“…It should be noted that, according to the results of previous studies, the frequency of the device in the present study was set at 50 Hz. 14,23 To conduct the experiments, three sets of coiled loops, each consisting of two loops (Figure 1, Zoom A), were made to generate an EMF. The coils were made from polytetrafluoroethylene, and the loops were 10 cm apart, separated by two glass Teflon.…”

“…The research by Provenzano et al showed that the 50-Hz sinusoidal frequency was one of the most effective frequencies to alter the growth and proliferation of Granulocytic cells. 14 Ma et al indicated that the growth and proliferation rate of bone-marrow stem cells under EMF of 3 mT sharply reduced after 3 days. 15 Liu et al studied the effect of the effective intensity on the growth of muscle cells in mice 16 and concluded that the intensity of 3 mT increased the growth and proliferation of muscle cells in mice.…”

“…Their findings revealed that cell growth and proliferation increased with enhancing the frequency. The research by Provenzano et al showed that the 50‐Hz sinusoidal frequency was one of the most effective frequencies to alter the growth and proliferation of Granulocytic cells 14 . Ma et al indicated that the growth and proliferation rate of bone‐marrow stem cells under EMF of 3 mT sharply reduced after 3 days 15 .…”

Fifty-Hertz low frequency magnetic field modifies sarcoplasmic reticulum function

“…In vitro studies, ELF MF have been reported to affect several basic cellular processes, such as cell proliferation [4], apoptosis [5], DNA and RNA synthesis [4,6], and gene transcription [7]. Since all these effects can be related more or less directly to the signal transduction pathways, Ca2+ as an intracellular critical second message has been of focus to scientists for many years [8][9][10][11][12].…”