Research Paper Volume 12, Issue 4 pp 3662—3681
Induction of apoptosis and ferroptosis by a tumor suppressing magnetic field through ROS-mediated DNA damage
- 1 Department of Central Laboratory, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China
Received: October 22, 2019 Accepted: January 27, 2020 Published: February 18, 2020
https://doi.org/10.18632/aging.102836How to Cite
Copyright © 2020 Yuan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
AC: alternating current; DDP: cisplatin; DCF-DA: 2’,7’-dichlorofluorescein diacetate; DC: direct current; DSB: double strand break; ELF-EMF: extremely low frequency electromagnetic field; EdU: 5-ethynyl-2'-deoxyuridine; Fer-1: ferrostatin-1; 5-FU: 5-fluorouracil; Hz: Hertz; HR: homologous recombination; MF: magnetic field; MDA: malondialdehyde; mT: militesla; NAC: N-acetyl-cysteine; NADPH: nicotinamide adenine dinucleotide phosphate; NHEJ: nonhomologous end-joining; PTX: paclitaxel; PARP: poly ADP-ribose polymerase; PCD: programmed cell death; ROS: reactive oxygen species; SSB: single strand break; SMF: static magnetic field; VCR: vincristine.