Sharpe Martyn A, Baskin David S, Pichumani Kumar, Ijare Omkar B, Helekar Santosh A
Kenneth R. Peak Center for Brain and Pituitary Tumor Treatment and Research, Houston Methodist Hospital, Houston, TX, United States.
Department of Neurosurgery, Houston Methodist Hospital, Houston, TX, United States.
Front Oncol. 2021 Nov 10;11:768758. doi: 10.3389/fonc.2021.768758. eCollection 2021.
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 (O) by isolated rat liver mitochondria, normal human astrocytes, and several patient derived brain tumor cells, and O generation/consumption by plant cells with an O electrode. We also investigated glucose metabolism in tumor cells using H and C 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.
电磁场（EMF）会提高细胞内活性氧（ROS）的水平，而ROS对癌细胞可能具有毒性。由于弱磁场会影响氧化还原活性自由基电子对中的自旋态配对，我们推测它们会破坏线粒体电子传递链（ETC）中的电子流动。我们通过研究一种新型非侵入性设备产生的振荡磁场（sOMF）的作用来验证这一假设，该设备包含以特定频率和时间模式旋转的永久磁铁。我们通过用氧电极测量分离的大鼠肝脏线粒体、正常人类星形胶质细胞和几种患者来源的脑肿瘤细胞的氧气（O）消耗，以及植物细胞的O生成/消耗，来研究sOMF对ETC的影响。我们还使用氢和碳核磁共振研究肿瘤细胞中的葡萄糖代谢，并使用MitoTracker™荧光显微镜和Caspase 3激活荧光探针评估导致细胞死亡的线粒体改变。我们发现，具有适当场强、频率和开/关模式的sOMF能完全阻止分离的、正在呼吸的大鼠肝脏线粒体以及患者来源的胶质母细胞瘤（GBM）、脑膜瘤和弥漫性内生脑桥胶质瘤（DIPG）细胞中的电子传递，并可导致线粒体完整性丧失。这些变化与癌细胞中线粒体碳通量的减少以及即使在细胞周期的非分裂阶段癌细胞的死亡相关。我们的研究结果表明，旋转磁场通过选择性破坏固定的ETC复合物中的电子流动，可能对GBM和DIPG等脑癌具有治疗效果。
