Effect of changing the alternating electric current frequency on the viability of human liver cancer cell line (HEPG2)

Different effects of alternating electric currents (AC) on biological materials have been observed depending on the frequency used. Extremely low frequencies (less than 1 KHz) produce electro-endocytosis at 500 Hz because of membrane depolarization. Intermediate frequencies coincide with tiny particle alignments and cell rotations (also known as the pearl chain effect), thus leading to the tumor-treating fields at 100–300 KHz. High frequencies (i.e., above several MHz) cause tissue heating to predominate due to the dielectric losses. This study investigates how exposure to a wide range of AC electric field frequencies affects the permeability and viability of hepatocellular carcinoma HEPG2 cells. With two silver/silver chloride electrodes, the cells were exposed to a square pulse with a magnitude of 0.4 V/cm at various frequencies between 1 Hz and 1 MHz. A dielectric properties measurement, flow cytometry analysis, fluorescent microscopy, and a polymerase chain reaction (PCR) gene expression analysis were performed. The results showed that all the exposed groups experienced a great reduction in the normal cells, with a clear increase in necrosis and apoptosis compared to the control group. It was noticed that the anti-tumoral effect of the examined frequency range was maximum at 10 KHz and 100 KHz. The permeability was increased in the groups exposed to frequencies above 1 kHz. The viability and permeability results were correlated to the electric relative permittivity, electric conductivity, and gene expression of cyclins A, B, and E.