TMET-64. Effect of Oncomagnetic Field on the Cellular Metabolism of Diffuse Midline Gliomas

Abstract Diffuse midline glioma (DMG), also known as diffuse intrinsic pontine glioma (DIPG) is a malignant pediatric brain tumor that cannot be surgically resected due to its location in the brainstem. Currently available treatment options are ineffective, and the median overall survival is 8-12 months. Currently, radiotherapy is the mainstay of treatment which adds 3-4 months to survival, and there is a great need for novel therapies for the treatment of DMG patients. We have devised a new noninvasive wearable device known as the Oncomagnetic device (OMD) which generates spinning oscillatory magnetic fields (OMF). OMF produces anticancer effects by disrupting mitochondrial electron transport chain, generating elevated levels reactive oxygen species (ROS) and caspase-dependent cell death. We have previously shown that OMF treatment in GBM cells generates superoxide and H2O2. We have also observed ROS generation in DMG cells with OMF treatment. Here, we investigated the effect of OMF on the cellular metabolism of H3.3K27M mutant DMG cells. Patient-derived H3.3K27M mutant DMG (SF8628) cells were grown in DMEM media, supplemented with 10% FBS and L-glutamine, under humidified air with 5% CO2 at 37 °C. When confluent, cells in the treatment group were stimulated with OMF for 4 hours. Cells in both control and test groups were harvested and extracted in 5% perchloric acid. 1H NMR spectroscopic data were collected on the cell extracts for metabolomic analysis. We observed a 3-fold increase in the glutathione (GSH) levels and a 2-fold increase in protein synthesis in OMF-treated DMG cells compared to the control group. The increase in the GSH levels is in response to the ROS generation in the DMG cells due to OMF treatment. On the other hand, the increase in protein levels could be attributed to the response of DMG cells to OMF-induced DNA damage and apoptosis. In conclusion, OMF treatment in DMG cells leads to ROS generation and apoptotic changes, resulting in metabolic changes including GSH production and protein synthesis.