Cellular stress response to extremely low‐frequency electromagnetic fields (ELF‐EMF): An explanation for controversial effects of ELF‐EMF on apoptosis

Impaired apoptosis is one of the hallmarks of cancer, and almost all of the non‐surgical approaches of eradicating tumour cells somehow promote induction of apoptosis. Indeed, numerous studies have stated that non‐ionizing non‐thermal extremely low‐frequency magnetic fields (ELF‐MF) can modulate the induction of apoptosis in exposed cells; however, much controversy exists in observations. When cells are exposed to ELF‐EMF alone, very low or no statistically significant changes in apoptosis are observed. Contrarily, exposure to ELF‐EMF in the presence of a co‐stressor, including a chemotherapeutic agent or ionizing radiation, can either potentiate or inhibit apoptotic effects of the co‐stressor. In our idea, the main point neglected in interpreting these discrepancies is “the cellular stress responses” of cells following ELF‐EMF exposure and its interplay with apoptosis. The main purpose of the current review was to outline the triangle of ELF‐EMF, the cellular stress response of cells and apoptosis and to interpret and unify discrepancies in results based on it. Therefore, initially, we will describe studies performed on identifying the effect of ELF‐EMF on induction/inhibition of apoptosis and enumerate proposed pathways through which ELF‐EMF exposure may affect apoptosis; then, we will explain cellular stress response and cues for its induction in response to ELF‐EMF exposure; and finally, we will explain why such controversies have been observed by different investigators. The outcome of cancer cells exposure to ELF‐EMF, as cellular stress response, is closely related to ER stress, NF‐κB inflammatory, Heat Shock Protein, Sirtuin, and DNA repair responses. The controversial evidence of ELF‐EMF‐induced apoptosis or autophagy in cancer cells has been hypothetically described by the way these cellular feedback happen.