Electrically induced proliferation manipulation of tumor cells.
Lilia Hafner 2016 Technical University of Munich, Abstract
Based on the hypothesis of Bingelli and Weinstein  that the transmembrane potential of different cells varies depending on the function of their detected proliferation, we analyzed the opposite effect and demonstrated that proliferation of cells is affected by electric fields . Thus, it should be clarified whether long-term effects in human tumor cells can be achieved in this way and whether therapeutically useful results are possible.
To explore whether and how electric fields affect cellular metabolism, proliferation, and morphology of tumor cells, we electrically stimulated human breast cancer cells (MCF-7) with low frequency square wave pulses of 100Hz frequency and harmonic field pulses of 100Hz and 150kHz. Analysis of the division of MCF-7 cells exposed to the low-frequency pulsed electric fields showed that their proliferation was reduced by 20% compared with untreated cells. Metabolic measurements of tumor cells electrically stimulated with harmonic field pulses showed an inhibitory effect on cell metabolism (oxygen consumption) of the treated groups. To avoid electrochemically induced side effects during direct stimulation, we also investigated how the cells behaved during direct electrical stimulation compared to stimulation with capacitively coupled electric fields. Finite element simulation was used to estimate what field strengths occur at the cellular level. Furthermore, it was demonstrated that cell volume reduction during direct stimulation was not caused by cytotoxic effects or corrosive effects. In addition, cell membrane potential measurements revealed hyperpolarization of one half of the cell and simultaneous depolarization of the other half. The potential fluctuation of the membrane (hyperpolarization/depolarization) seems to have a great influence on the proliferation of tumor cells . Therefore, it can be assumed that the connection between the potential membrane fluctuation caused by the externally applied electric field and the cellular division activity is real. A relationship between ion channels, possible membrane variation induced by these channels, and possible tumor growth inhibition has not yet been established. It was also confirmed that acidosis in the extracellular area leads to inhibition of proliferation on the one hand and membrane depolarization on the other. This is probably caused by the intracellular pH-regulating mechanisms.
In addition, the use of Na+/H+
exchanger blocker (amiloride) was investigated. It causes a slight membrane yperpolarization in the context of increasing extracellular acidosis. The resulting inhibition of proliferation is more pronounced than in the control group (untreated cells). Consequently, it can be suggested that the relationship between extracellular acidosis, membrane depolarization, and inhibition of proliferation does exist. However, the hypothesis of Binggeli and Weinstein  confirms, however, the existence of a correlation between the
Hyperpolarization of the membrane and inhibition of proliferation.But this antithesis does not give us a sufficient understanding of the mechanism of action between depolarization/hyperpolarization and proliferation within extracellular acidosis. Presumably, there are some mechanisms in vivo that cannot be detected by studying in vitro cell cultures. examination of in vitro cell cultures cannot be detected.
Link to the study: https://mediatum.ub.tum.de/1286643