Pulsed Low-Frequency Magnetic Fields Induce Tumor Membrane Disruption and Altered Cell Viability.

Author: Ashdown CP1, Johns SC2, Aminov E3, Unanian M4, Connacher W3, Friend J3, Fuster MM5
Affiliation:
1VA San Diego Healthcare System, San Diego, California; Division of Biological Sciences, University of California, San Diego, La Jolla, California.
2VA San Diego Healthcare System, San Diego, California; Veterans Medical Research Foundation, San Diego, California.
3Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, California.
4School of Electrical Engineering, Columbia University, New York, New York.
5VA San Diego Healthcare System, San Diego, California; Veterans Medical Research Foundation, San Diego, California; Department of Medicine, Division of Pulmonary & Critical Care, University of California, San Diego, La Jolla, California; Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California. Electronic address: mfuster@ucsd.edu.
Conference/Journal: Biophys J.
Date published: 2020 Feb 18
Other: Pages: S0006-3495(20)30134-X , Special Notes: doi: 10.1016/j.bpj.2020.02.013. [Epub ahead of print] , Word Count: 277


Tumor cells express a unique cell surface glycocalyx with upregulation of sulfated glycosaminoglycans and charged glycoproteins. Little is known about how electromagnetic fields interact with this layer, particularly with regard to harnessing unique properties for therapeutic benefit. We applied a pulsed 20-millitesla (mT) magnetic field with rate of rise (dB/dt) in the msec range to cultured tumor cells to assess whether this affects membrane integrity as measured using cytolytic assays. A 10-min exposure of A549 human lung cancer cells to sequential 50- and 385-Hz oscillating magnetic fields was sufficient to induce intracellular protease release, suggesting altered membrane integrity after the field exposure. Heparinase treatment, which digests anionic sulfated glycan polymers, before exposure rendered cells insensitive to this effect. We further examined a non-neoplastic human primary cell line (lung lymphatic endothelial cells) as a typical normal host cell from the lung cancer microenvironment and found no effect of field exposure on membrane integrity. The field exposure was also sufficient to alter proliferation of tumor cells in culture, but not that of normal lymphatic cells. Pulsed magnetic field exposure of human breast cancer cells that express a sialic-acid rich glycocalyx also induced protease release, and this was partially abrogated by sialidase pretreatment, which removes cell surface anionic sialic acid. Scanning electron microscopy showed that field exposure may induce unique membrane "rippling" along with nanoscale pores on A549 cells. These effects were caused by a short exposure to pulsed 20-mT magnetic fields, and future work may examine greater magnitude effects. The proof of concept herein points to a mechanistic basis for possible applications of pulsed magnetic fields in novel anticancer strategies.

Published by Elsevier Inc.

PMID: 32142642 DOI: 10.1016/j.bpj.2020.02.013

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