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

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.