Induction of apoptosis and ferroptosis by a tumor suppressing magnetic field through ROS-mediated DNA damage

Abstract

Magnetic field (MF) is being used in antitumor treatment; however, the underlying biological mechanisms remain unclear. In this study, the potency and mechanism of a previously published tumor suppressing MF exposure protocol were further investigated. This protocol, characterized as a 50 Hz electromagnetic field modulated by static MF with time-average intensity of 5.1 mT, when applied for 2 h daily for over 3 consecutive days, selectively inhibited the growth of a broad spectrum of tumor cell lines including lung cancer, gastric cancer, pancreatic cancer and nephroblastoma. The level of intracellular reactive oxygen species (ROS) increased shortly after field exposure and persisted. Subsequently, pronounced DNA damage and activation of DNA repair pathways were identified both in vitro and in vivo. Furthermore, use of free radical scavenger alleviated DNA damage and partially reduced cell death. Finally, this field was found to inhibit cell proliferation, and simultaneously induced two types of programmed cell death, apoptosis and ferroptosis. In conclusion, this tumor suppressing MF could determine cell fate through ROS-induced DNA damage, inducing oxidative stress and activation of the DNA damage repair pathways, eventually lead to apoptosis and ferroptosis, as well as inhibition of tumor growth.

Melatonin Alleviates Acute Sleep Deprivation-Induced Memory Loss in Mice by Suppressing Hippocampal Ferroptosis

“…Excess active iron donates electrons, leading to ROS generation through the Fenton reaction, promoting lipid peroxidation and initiating ferroptosis (Dixon and Stockwell, 2014). Many researchers believe that ROS and MDA accumulation reflect the progress of cellular ferroptosis (Yamada et al, 2020;Yuan et al, 2020), while GPX4 and SOD are key antioxidant enzymes for scavenging excess ROS and MDA (Galaris et al, 2019). The role of GPX4 in ferroptosis is particularly important, studies reported that deletion of GPX4 in forebrain neurons promotes cognitive impairment and neurodegeneration (Hambright et al, 2017).…”

Non-Heating Alternating Magnetic Field Nanomechanical Stimulation of Biomolecule Structures via Magnetic Nanoparticles as the Basis for Future Low-Toxic Biomedical Applications

“…Experiments on cells and cell cultures showed the effectiveness of NMMA as a means of inducing apoptosis in cancer cells [ 36 , 37 , 41 , 42 ]. In addition, there is indirect evidence of the possible participation of drugs containing iron ions, or natural iron-containing proteins-ferritins, in the mechanisms of MF action in vivo [ 138 , 139 , 140 , 141 ]. Of course, for a reliable proof of the magnetomechanical origin of the effects observed in vivo, it is necessary to conduct targeted experiments with the introduction of optimally designed MNPs, with known magnetic characteristics and functional shells, into the body, as well as physically substantiated parameters of the activating AMF.…”

Serine-70 phosphorylated Bcl-2 prevents oxidative stress-induced DNA damage by modulating the mitochondrial redox metabolism

“…Given that ROS is implicated in S-phase progression ( 43 , 44 ), where DNA is prone to damage ( 45–47 ), it is tempting to speculate that S70pBcl2 is the key to preventing DNA damage by reducing ROS, subsequent ROS-dependent G1/S phase transition and Ri-DNA damage. In addition, it is noted that ROS and Ri-DNA damage are upstream signals to different types of cell death such as apoptosis, necroptosis, ferroptosis or even cellular senescence ( 11 , 12 , 37 , 48–52 ). Thus, it is likely that the protective redox sensing and modulating functions of S70pBcl2 may not only be affecting the conventional apoptosis but also other types of ROS- and Ri-DNA-mediated cell deaths.…”