Power frequency magnetic field promotes a more malignant phenotype in neuroblastoma cells via redox-related mechanisms

Abstract

In accordance with the classification of the International Agency for Research on Cancer, extremely low frequency magnetic fields (ELF-MF) are suspected to promote malignant progression by providing survival advantage to cancer cells through the activation of critical cytoprotective pathways. Among these, the major antioxidative and detoxification defence systems might be targeted by ELF-MF by conferring cells significant resistance against clinically-relevant cytotoxic agents. We investigated whether the hyperproliferation that is induced in SH-SY5Y human neuroblastoma cells by a 50 Hz, 1 mT ELF magnetic field was supported by improved defence towards reactive oxygen species (ROS) and xenobiotics, as well as by reduced vulnerability against both H2O2 and anti-tumor ROS-generating drug doxorubicin. ELF-MF induced a proliferative and survival advantage by activating key redox-responsive antioxidative and detoxification cytoprotective pathways that are associated with a more aggressive behavior of neuroblastoma cells. This was coupled with the upregulation of the major sirtuins, as well as with increased signaling activity of the erythroid 2-related nuclear transcription factor 2 (NRF2). Interestingly, we also showed that the exposure to 50 Hz MF as low as 100 µT may still be able to alter behavior and responses of cancer cells to clinically-relevant drugs.

50‐Hz MF does not affect global DNA methylation of SH‐SY5Y cells treated with the neurotoxin MPP+

“…Even though the possible association of ELF‐MF exposure with neurodegenerative diseases is still a matter of debate, experimental studies identifying the potential etiopathogenetic mechanisms elicited by ELF are still few. In this context, a key role of ELF in prompting neuronal damage has been assigned to redox imbalance, extensively documented in neuronal experimental systems, including SH‐SY5Y cells [Di Loreto et al, ; Luukkonen et al, ; Consales et al, ; Mattsson and Simkó, Falone et al, ]. We previously demonstrated that 50‐Hz MF (1 mT) triggers oxidative stress, protein carbonylation, and neuronal cell death, and sensitizes SH‐SY5Y cells to the PD MPP + neurotoxin in vitro [Benassi et al, ], thus highlighting a possible detrimental effect elicited by ELF in predisposing neurons to degeneration.…”

The antitumor effect of static and extremely low frequency magnetic fields against nephroblastoma and neuroblastoma

“…In most occasions, the goals were to study the epidemiology of low intensity ELF MF [Kesari et al, ; Höytö et al, ]. Continuous exposure, low intensity ELF MF seems to induce hyperproliferation of neuroblastoma cells [Trillo et al, ; Falone et al, ], supporting the IARC definition of EMF/MF as potential carcinogens. A 75 Hz, 2 mT MF lowered the proliferation rate of neuroblastoma SH‐SY5Y cells [Osera et al, ].…”

Case-Control Study on Occupational Exposure to Extremely Low-Frequency Electromagnetic Fields and the Association with Meningioma

“…In a recent study ELF-EMF promoted a more malignant phenotype in neuroblastoma cells [ 27 ]. ELF-EMF induced a proliferative and survival advantage by activating key redox-responsive antioxidative and detoxification cytoprotective pathways associated with a more aggressive behaviour of neuroblastoma cells.…”