Little strokes fell big oaks: The use of weak magnetic fields and reactive oxygen species to fight cancer

Abstract

The increase in early-stage cancers, particularly gastrointestinal, breast and kidney cancers, has been linked to lifestyle changes such as consumption of processed foods and physical inactivity, which contribute to obesity and diabetes - major cancer risk factors. Conventional treatments such as chemotherapy and radiation often lead to severe long-term side effects, including secondary cancers and tissue damage, highlighting the need for new, safer and more effective therapies, especially for young patients. Weak electromagnetic fields (WEMF) offer a promising non-invasive approach to cancer treatment. While WEMF have been used therapeutically for musculoskeletal disorders for decades, their role in oncology is still emerging. WEMFs affect multiple cellular processes through mechanisms such as the radical pair mechanism (RPM), which alters reactive oxygen species (ROS) levels, mitochondrial function, and glycolysis, among others. This review explores the potential of WEMF in conjunction with reactive oxygen species as a cancer therapy, highlighting WEMFs selective targeting of cancer cells and its non-ionizing nature, which could reduce collateral damage compared to conventional treatments. In addition, synchronization of WEMF with circadian rhythms may further enhance its therapeutic efficacy, as has been demonstrated in other cancer therapies.

Keywords: Cancer therapy; Circadian rhythm; Hypoxia; Public health; ROS; Radical pair mechanism; Weak magnetic fields.

Fig. 1

The radical pair mechanism (RPM) in the context of cellular flavoproteins. FAD in its excited state forms a radical pair (RP, [FADH•A•]) by donating an electron (e^-) to an acceptor molecule (A). The resulting unpaired electrons of each radical, FAD• and A•, remain spin correlated despite the spatial separation and can therefore assemble in two states, a singlet state where the spins (circled arrows) of the electrons are opposing (blue), or a triplet state where the spins align in parallel (red). These states oscillate between each other at a high frequency (singlet-triplet interconversion). The presence of a weak magnetic field alters the spin recombination dynamics of this interconversion, affecting the amounts of singlet (H₂O₂) or triplet (superoxide) product formation and, thus, the resulting H₂O₂/O₂^•- ratio. Accordingly, cellular H₂O₂/O₂^•- ratios can be manipulated by WEMF of specific intensities, which have to match the spin energy levels of electrons. ROS-dependent signaling pathways, such as those involved in cellular bioenergetics, consequently respond to WEMF-induced changes in cellular ROS partitioning. In case of avian magnetoreception, the most agreed acceptors are tryptophan residues located in the CRY proteins [45] or superoxide [46]. In mammalian cells flavin-superoxide radical pairs were demonstrated to be responsible for WEMF induced effects [[47], [48], [49]]. Circled arrows indicate the spins of the electrons in the singlet ground and excited states of FAD and the singlet and triplet states of RP, respectively.

Fig. 2

Timed application of weak magnetic fields to tumor cells may optimize therapeutic outcomes. Circadian rhythms in tumor cells are important because they influence cellular redox states and metabolic processes. Treatments such as radiation or chemotherapy, when administered according to the circadian clock - referred to as chronotherapy - can produce different results depending on the time of day. Weak electromagnetic fields can modify the oscillation of the circadian clock, e.g. they can enhance the oscillation when applied during the day (A), while the same treatment applied during the early night completely stops these oscillations (B). This modulation of circadian rhythms can affect drug metabolism, mitochondrial respiration, and ROS production leading to cell death or potentially enhance the efficacy of chemotherapeutic agents. Thus, timing treatments according to circadian rhythms may optimize therapeutic outcomes while minimizing adverse effects.

Fig. 3

The orientation of a radiofrequency (RF) to a static electromagnetic field impacts cellular metabolism and reactive oxygen species (ROS) production. When a low-intensity static magnetic field (e.g., 50 μT) is combined with a radiofrequency (RF) signal at Zeeman resonance (1.4 MHz), the orientation of the RF affects cellular metabolism in two distinct ways: (A) When the RF is aligned parallel to the static field, mitochondrial respiration increases, leading to higher production of reactive oxygen species (ROS). Elevated ROS can cause DNA damage, which may result in cell death or enhance the efficacy of chemotherapeutic drugs that induce DNA damage. (B) When the RF is oriented perpendicular to the static field, mitochondrial respiration remains unchanged, but glycolysis increases. This indicates a metabolic shift towards anaerobic energy production.