Abstract
Purpose
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).
Methods
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.
Results
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.
Conclusion
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.
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Data and material will be made available to all researchers upon request.
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Acknowledgements
The authors are grateful to the many patients and their families who have given permission to use their tissues in our studies. They thank Fabio Henrique Brasil da Costa for assistance with one of the experiments, and Lisa Nguyen, Blessy S. John, and Alvin Saldon for constructing the OMF delivering apparatuses used in all experiments.
Funding
This work was supported by a grant from the Translational Research Initiative of the Houston Methodist Research Institute to SAH and DSB; Funding from Kenneth R. Peak Foundation, John S. Dunn Foundation, Taub Foundation, Blanche Green Fund of the Pauline Sterne Wolff Memorial Foundation, Kelly Kicking Cancer Foundation, Methodist Hospital Foundation, Veralan Foundation, and many contributions in honor of Will McKone to DSB. The John S. Dunn Foundation also supports the Distinguished Professorship of MAS.
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Study design: SAH, MAS and KP; conduct of experiments: SH, MAS, and OBI; data analysis and presentation: SH, MAS, SAH and OBI; manuscript preparation: SAH, SH and OBI; interpretation of results and discussion: all authors.
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SAH, DSB, MAS and KP are listed as inventors on a U.S. patent application filed by Houston Methodist Hospital. The other authors declare no conflicts of interest.
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Informed consent for tumor tissue was obtained from the patients in accordance with an approved Houston Methodist Research Institute Institutional Review Board protocol.
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Helekar, S.A., Hambarde, S., Ijare, O.B. et al. Selective induction of rapid cytotoxic effect in glioblastoma cells by oscillating magnetic fields. J Cancer Res Clin Oncol 147, 3577–3589 (2021). https://doi.org/10.1007/s00432-021-03787-0
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DOI: https://doi.org/10.1007/s00432-021-03787-0