Rotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells

Electromagnetic fields (EMF) raise intracellular levels of reactive oxygen species (ROS) that can be toxic to cancer cells. Because weak magnetic fields influence spin state pairing in redox-active radical electron pairs, we hypothesize that they disrupt electron flow in the mitochondrial electron t...

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Autores principales:	Martyn A. Sharpe, David S. Baskin, Kumar Pichumani, Omkar B. Ijare, Santosh A. Helekar
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	radical pair mechanism cancer oxygen consumption electron transport chain diffuse intrinsic pontine glioma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/94fb975157344b4393de38b79e10c8c6
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spelling	oai:doaj.org-article:94fb975157344b4393de38b79e10c8c62021-11-10T06:31:00ZRotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells2234-943X10.3389/fonc.2021.768758https://doaj.org/article/94fb975157344b4393de38b79e10c8c62021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.768758/fullhttps://doaj.org/toc/2234-943XElectromagnetic fields (EMF) raise intracellular levels of reactive oxygen species (ROS) that can be toxic to cancer cells. Because weak magnetic fields influence spin state pairing in redox-active radical electron pairs, we hypothesize that they disrupt electron flow in the mitochondrial electron transport chain (ETC). We tested this hypothesis by studying the effects of oscillating magnetic fields (sOMF) produced by a new noninvasive device involving permanent magnets spinning with specific frequency and timing patterns. We studied the effects of sOMF on ETC by measuring the consumption of oxygen (O2) by isolated rat liver mitochondria, normal human astrocytes, and several patient derived brain tumor cells, and O2 generation/consumption by plant cells with an O2 electrode. We also investigated glucose metabolism in tumor cells using 1H and 13C nuclear magnetic resonance and assessed mitochondrial alterations leading to cell death by using fluorescence microscopy with MitoTracker™ and a fluorescent probe for Caspase 3 activation. We show that sOMF of appropriate field strength, frequency, and on/off profiles completely arrest electron transport in isolated, respiring, rat liver mitochondria and patient derived glioblastoma (GBM), meningioma and diffuse intrinsic pontine glioma (DIPG) cells and can induce loss of mitochondrial integrity. These changes correlate with a decrease in mitochondrial carbon flux in cancer cells and with cancer cell death even in the non-dividing phase of the cell cycle. Our findings suggest that rotating magnetic fields could be therapeutically efficacious in brain cancers such as GBM and DIPG through selective disruption of the electron flow in immobile ETC complexes.Martyn A. SharpeMartyn A. SharpeMartyn A. SharpeDavid S. BaskinDavid S. BaskinDavid S. BaskinDavid S. BaskinKumar PichumaniKumar PichumaniKumar PichumaniKumar PichumaniOmkar B. IjareOmkar B. IjareOmkar B. IjareSantosh A. HelekarSantosh A. HelekarSantosh A. HelekarSantosh A. HelekarFrontiers Media S.A.articleradical pair mechanismcanceroxygen consumptionelectron transport chaindiffuse intrinsic pontine gliomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	radical pair mechanism cancer oxygen consumption electron transport chain diffuse intrinsic pontine glioma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	radical pair mechanism cancer oxygen consumption electron transport chain diffuse intrinsic pontine glioma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Martyn A. Sharpe Martyn A. Sharpe Martyn A. Sharpe David S. Baskin David S. Baskin David S. Baskin David S. Baskin Kumar Pichumani Kumar Pichumani Kumar Pichumani Kumar Pichumani Omkar B. Ijare Omkar B. Ijare Omkar B. Ijare Santosh A. Helekar Santosh A. Helekar Santosh A. Helekar Santosh A. Helekar Rotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells
description	Electromagnetic fields (EMF) raise intracellular levels of reactive oxygen species (ROS) that can be toxic to cancer cells. Because weak magnetic fields influence spin state pairing in redox-active radical electron pairs, we hypothesize that they disrupt electron flow in the mitochondrial electron transport chain (ETC). We tested this hypothesis by studying the effects of oscillating magnetic fields (sOMF) produced by a new noninvasive device involving permanent magnets spinning with specific frequency and timing patterns. We studied the effects of sOMF on ETC by measuring the consumption of oxygen (O2) by isolated rat liver mitochondria, normal human astrocytes, and several patient derived brain tumor cells, and O2 generation/consumption by plant cells with an O2 electrode. We also investigated glucose metabolism in tumor cells using 1H and 13C nuclear magnetic resonance and assessed mitochondrial alterations leading to cell death by using fluorescence microscopy with MitoTracker™ and a fluorescent probe for Caspase 3 activation. We show that sOMF of appropriate field strength, frequency, and on/off profiles completely arrest electron transport in isolated, respiring, rat liver mitochondria and patient derived glioblastoma (GBM), meningioma and diffuse intrinsic pontine glioma (DIPG) cells and can induce loss of mitochondrial integrity. These changes correlate with a decrease in mitochondrial carbon flux in cancer cells and with cancer cell death even in the non-dividing phase of the cell cycle. Our findings suggest that rotating magnetic fields could be therapeutically efficacious in brain cancers such as GBM and DIPG through selective disruption of the electron flow in immobile ETC complexes.
format	article
author	Martyn A. Sharpe Martyn A. Sharpe Martyn A. Sharpe David S. Baskin David S. Baskin David S. Baskin David S. Baskin Kumar Pichumani Kumar Pichumani Kumar Pichumani Kumar Pichumani Omkar B. Ijare Omkar B. Ijare Omkar B. Ijare Santosh A. Helekar Santosh A. Helekar Santosh A. Helekar Santosh A. Helekar
author_facet	Martyn A. Sharpe Martyn A. Sharpe Martyn A. Sharpe David S. Baskin David S. Baskin David S. Baskin David S. Baskin Kumar Pichumani Kumar Pichumani Kumar Pichumani Kumar Pichumani Omkar B. Ijare Omkar B. Ijare Omkar B. Ijare Santosh A. Helekar Santosh A. Helekar Santosh A. Helekar Santosh A. Helekar
author_sort	Martyn A. Sharpe
title	Rotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells
title_short	Rotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells
title_full	Rotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells
title_fullStr	Rotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells
title_full_unstemmed	Rotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells
title_sort	rotating magnetic fields inhibit mitochondrial respiration, promote oxidative stress and produce loss of mitochondrial integrity in cancer cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/94fb975157344b4393de38b79e10c8c6
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Rotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells

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