DNAR-03. ONCOMAGNETIC TREATMENT KILLS GLIOMA CELLS BY INHIBITING MITOCHONDRIAL ELECTRON TRANSPORT AND BY INDUCING OXIDATIVE STRESS AND DNA DAMAGE

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 Optune® device approved by the FDA and provides a novel approach for CNS tumor treatment. In 7 end-stage GBM patients, this device reversed the progression of recurrent tumors causing >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 marked reduction in tumor size, increased survival (p< 0.05, n = 9) and greater DNA damage (γ-H2AX foci) in 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-I and markedly increased reactive oxygen species (ROS) levels in GBM cells. Detection of γ-H2AX and 53BP1 foci showed that sOMF caused 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 4 h caused cell cycle arrest in the G1 phase and 30% - 40% loss of surviving colonies detected by clonogenic cell survival assay, while normal SVGp12 cells were not affected. 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.