EXTH-13. Inhibition of mitochondrial electron transport, induction of oxidative stress, and DNA damage by oncomagnetic device in GBM cancer cells

Abstract A new noninvasive cancer therapeutic device developed in our laboratory, called the Oncomagnetic device, involves repeated stimulation with oscillating magnetic fields (sOMF) produced by spinning permanent magnets. It is technologically and mechanistically distinct from the FDA-approved Optune device and provides a novel approach for treating CNS tumors. In 7 end-stage GBM patients, this device reversed the progression of recurrent tumors, resulting in a >30% reduction in their contrast-enhanced volumes within 4–8 weeks of treatment. Immune-competent mice with implanted mouse glioma cells in their brains also showed a marked decrease in tumor size, increased survival (p< 0.05, n = 9), and greater DNA damage (g-H2AX foci) in the implanted tumor after sOMF treatment. Normal mice exposed to sOMF for 4 months had no adverse effects on the brain and other organs. In vitro, sOMF inhibited mitochondrial ETC complex-1 and markedly increased reactive oxygen species (ROS) levels in GBM cells. Detection of g-H2AX and 53BP1 foci revealed that sOMF induced significant DNA damage in GBM cells and diffuse intrinsic pontine glioma (DIPG) cells but not in normal astroglial SVGp12 cells. GBM cells exposed to sOMF for four hours resulted in cell cycle arrest in the G1 phase and a 30-40% loss of surviving colonies, as detected by a clonogenic cell survival assay, whereas normal SVGp12 cells were unaffected. This loss of survival in GBM cells was rescued by the antioxidant Trolox. These results indicate that sOMF stimulation has high anticancer potency comparable to low-dose radiation therapy at the cellular level, with an underlying mechanism of action that is substantially different from that proposed for Optune® TTF.