Abstract
Electromagnetic fields (EMF) raise intracellular levels of reactive oxygen species (ROS) that can be toxic to cancer cells. Because weak magnetic fields influence spin state pairing in redox-active radical electron pairs, we hypothesize that they disrupt electron flow in the mitochondrial electron transport chain (ETC). We tested this hypothesis by studying the effects of oscillating magnetic fields (sOMF) produced by a new noninvasive device involving permanent magnets spinning with specific frequency and timing patterns. We studied the effects of sOMF on ETC by measuring the consumption of oxygen (O2) by isolated rat liver mitochondria, normal human astrocytes, and several patient derived brain tumor cells, and O2 generation/consumption by plant cells with an O2 electrode. We also investigated glucose metabolism in tumor cells using 1H and 13C nuclear magnetic resonance and assessed mitochondrial alterations leading to cell death by using fluorescence microscopy with MitoTracker™ and a fluorescent probe for Caspase 3 activation. We show that sOMF of appropriate field strength, frequency, and on/off profiles completely arrest electron transport in isolated, respiring, rat liver mitochondria and patient derived glioblastoma (GBM), meningioma and diffuse intrinsic pontine glioma (DIPG) cells and can induce loss of mitochondrial integrity. These changes correlate with a decrease in mitochondrial carbon flux in cancer cells and with cancer cell death even in the non-dividing phase of the cell cycle. Our findings suggest that rotating magnetic fields could be therapeutically efficacious in brain cancers such as GBM and DIPG through selective disruption of the electron flow in immobile ETC complexes.
Highlights
Electromagnetic fields (EMF) are known to produce anticancer effects in vitro and in vivo [1]
In a recent publication we have shown that oncomagnetic studying the effects of oscillating magnetic fields (sOMF) have a differential effect on cancer cells, when compared with cells derived from normal tissues [2]. sOMF stimulation of GBM and lung cancer cells causes death, and cell death is associated with mitochondrial superoxide generation, oxidation of the glutathione, an increasing GSSG/GSH ratio and the activation of the apoptotic caspase-3/7 cascade
We have previously demonstrated that sOMF treatment of cells generates superoxide/hydrogen peroxide in the mitochondrial matrix [2], and Succinate Dehydrogenase (SDH) is a site of mitochondrial superoxide generation [23, 33]
Summary
Electromagnetic fields (EMF) are known to produce anticancer effects in vitro and in vivo [1]. Pairing of electrons in bimolecular reactions and electron transfer processes with free radical intermediates, termed as the radical pair mechanism (RPM), is perturbed by magnetic fields in the milliTesla (mT) and microTesla (μT) ranges [3,4,5,6]. This perturbation is due to a quantum mechanical phenomenon in which the spin of an electron tends to align itself with the axis of a magnet. The singlettriplet interconversion rate of an electron is strongly influenced by an externally applied magnetic field and the magnetic fields of its neighboring atomic nuclei (hyperfine interactions)
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