TMS-Like Magnetic Fields Modulate Metabolic Activity of Hepatic and Colorectal Cancer Cells

Abstract

Transcranial magnetic stimulation (TMS) is a widely available technology employing relatively strong (up to 4 T) pulsed (up to 300 Hz) magnetic fields for diagnostics of brain functions and treatment of various brain disorders. The current paradigm implies that the magnetic induction of Eddy currents in the brain neurons is the leading biological mechanism of TMS. At the same time, it is almost unknown how the TMS-like magnetic fields act on nonneuronal cells. Here, we explored the effects of TMS-like repetitive magnetic stimulation (RMS) on metabolic activity of human colorectal cancer (CRC) and hepatocellular carcinoma (HCC) cells. The HCT116 (CRC) and HuH7 (HCC) <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vitro</i> cell cultures were treated using a TMS device “Magstim Rapid <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ” with an air-cooled “Magstim” figure-eight coil (AFC70). Five intermittent RMS (iRMS) and two burst RMS (bRMS) experimental protocols were applied to the monolayers of the cells as a single treatment session. The activity of succinate dehydrogenase, an enzyme essential for energy production in mitochondria, was measured by 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric viability assay in 24 h post-stimulation. Compared to untreated control, in HCT116 cells, a low-frequency iRMS treatment ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$f $ </tex-math></inline-formula> = 1 Hz, 600 pulses, <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$B $ </tex-math></inline-formula> = 0.8 T) induced a statistically significant decrease in metabolic activity (viability), while the high-frequency iRMS and bRMS increased it. In HuH7 cells, all tested RMS protocols either did not change or stimulated the metabolic activity (viability) of the cells, in comparison to the untreated control. The analysis of correlations revealed the almost opposite trends in CRC and HCC cells response to the frequency, temporal patterns, and magnetic field flux density considered as the parameters of the experimental RMS. Our findings demonstrate the tumor type- and stimulation protocol-specific effects of the repurposed TMS technology on colorectal and liver cancer cells. The underlying mechanism of these differences requires further study. The current results indicate that TMS-like magnetic fields may have new potential applications as an adjuvant anticancer treatment modality.