Selective induction of rapid cytotoxic effect in glioblastoma cells by oscillating magnetic fields.

Abstract

The mechanisms underlying anticancer effects of electromagnetic fields are poorly understood. An alternating electric field-generating therapeutic device called Optune™ device has been approved for the treatment of glioblastoma (GBM). We have developed a new device that generates oscillating magnetic fields (OMF) by rapid rotation of strong permanent magnets in specially designed patterns of frequency and timing and have used it to treat an end-stage recurrent GBM patient under an expanded access/compassionate use treatment protocol. Here, we ask whether OMF causes selective cytotoxic effects in GBM and whether it is through generation of reactive oxygen species (ROS). We stimulated patient derived GBM cells, lung cancer cells, normal human cortical neurons, astrocytes, and bronchial epithelial cells using OMF generators (oncoscillators) of our Oncomagnetic Device and compared the results to those obtained under unstimulated or sham-stimulated control conditions. Quantitative fluorescence microscopy was used to assess cell morphology, viability, and ROS production mechanisms. We find that OMF induces highly selective cell death of patient derived GBM cells associated with activation of caspase 3, while leaving normal tissue cells undamaged. The cytotoxic effect of OMF is also seen in pulmonary cancer cells. The underlying mechanism is a marked increase in ROS in the mitochondria, possibly in part through perturbation of the electron flow in the respiratory chain. Rotating magnetic fields produced by a new noninvasive device selectively kill cultured human glioblastoma and non-small cell lung cancer cells by raising intracellular reactive oxygen species, but not normal human tissue cells.