An Open Question: Is Non-Ionizing Radiation a Tool for Controlling Apoptosis-Induced Proliferation?

Abstract

Non-ionizing radiation is commonly used in the clinical setting, despite its known ability to trigger oxidative stress and apoptosis, which can lead to damage and cell death. Although induction of cell death is typically considered harmful, apoptosis can also be beneficial in the right context. For example, cell death can serve as the signal for new tissue growth, such as in apoptosis-induced proliferation. Recent data has shown that exposure to non-ionizing radiation (such as weak static magnetic fields, weak radiofrequency magnetic fields, and weak electromagnetic fields) is able to modulate proliferation, both in cell culture and in living organisms (for example during tissue regeneration). This occurs via in vivo changes in the levels of reactive oxygen species (ROS), which are canonical activators of apoptosis. This review will describe the literature that highlights the tantalizing possibility that non-ionizing radiation could be used to manipulate apoptosis-induced proliferation to either promote growth (for regenerative medicine) or inhibit it (for cancer therapies). However, as uncontrolled growth can lead to tumorigenesis, much more research into this exciting and developing area is needed in order to realize its promise.

A 50 Hz magnetic field influences the viability of breast cancer cells 96 h after exposure

“…Notably, a small production of ROS can lead to an increase in cell proliferation while an excess of them would lead to cell damage and reduced proliferation [ 44 , 45 ]. ROS production in turn can act as a potent regulator of MAPKs signaling cascade [ 46 , 47 ]. A low intensity and/or short-term exposure to ELF-MF may lead to a slight increase in ROS levels that constitute a cellular proliferative stimulus if are mantained in a physiological range (e.g.…”

“…A low intensity and/or short-term exposure to ELF-MF may lead to a slight increase in ROS levels that constitute a cellular proliferative stimulus if are mantained in a physiological range (e.g. they are counteracted by the cellular antioxidant systems) [ 46 ]. Conversely, a higher increase in ROS associated with higher ELF-MF intensity and longer exposure time may lead to a ROS ammount that if it exceeds a critical threshold the cellular oxidative damage prevails decreasing cellular proliferation [ 46 ].…”

“…they are counteracted by the cellular antioxidant systems) [ 46 ]. Conversely, a higher increase in ROS associated with higher ELF-MF intensity and longer exposure time may lead to a ROS ammount that if it exceeds a critical threshold the cellular oxidative damage prevails decreasing cellular proliferation [ 46 ]. The effect on ROS production may be present even after 96 h of exposure except in MCF-7 cells.…”

Biophysics at the edge of life and death: Radical control of apoptotic mechanisms

“…These data demonstrate that many diverse cell types are responsive to MFs in physiologically meaningful ways. Thus, subatomic control of apoptosis and apoptosis-induced proliferation through quantum effects has been proposed as an exciting new avenue of therapeutic research (Hack et al, 2021). Likely the strongest benefit of this approach is the potential to tune applications of MFs to use some field strengths to remove unwanted cells and different field strengths to increase proliferation in regenerative or growth promoting settings.…”

Impact of weak radiofrequency and static magnetic fields on key signaling molecules, intracellular pH, membrane potential, and cell growth in HT-1080 fibrosarcoma cells

“…Singlet state allows for recombination which yields reduced ROS levels. On the other hand, triplet state allows for diffusion of radicals which yields increased ROS levels 28 . It has been shown that, in principle, applied weak magnetic fields can raise the yield of free radicals and abolish recombination between 10 and 40% 29 .…”