Inhibition of mitochondrial <scp>NADH</scp> :ubiquinone oxidoreductase by spinning oscillating magnetic fields causes toxicity in cancer cells

A newly developed noninvasive Oncomagnetic device (OMD) causes selective cytotoxicity in glioblastoma and diffuse intrinsic pontine glioma cells, providing a novel, non-toxic approach to anticancer therapy. Here, we report results in cultured glioma cells and in a syngeneic mouse model indicating that the immediate intracellular target mechanism of action of the spinning oscillating magnetic field (sOMF) produced by this device is reactive oxygen species-dependent persistent inhibition of mitochondrial complex I. Steps downstream of this mechanism involve the production of oxidative stress, DNA damage, G1 phase cell cycle arrest, and caspase-dependent apoptosis. We also show that sOMF does not produce these effects in normal human astrocytes and astroglial cells. These data provide a rationale for safe clinical use of OMD.