Response of Human Malignant Glioma Cells to Asymmetric Bipolar Electrical Impulses

Abstract

Electric and electromagnetic pulses have been shown to enhance the endocytosis rate, with all-or-nothing responses beyond a field strength threshold and linear responses as a function of field strength and treatment duration utilizing bipolar symmetrical and monopolar pulses, respectively. Malignant glioma (MG) is resistant to chemotherapy. The present study looked for a new electrical impulse that can aid electrochemotherapy to deliver anticancer drugs while using less electrical energy. Bipolar asymmetric electric pulses were applied to U251MG cells suspended in physiologically conductive media in the presence of molecular probes, including Bleomycin. The delivered electric pulses with a pulse duration range of 180-500 µs and a frequency range of 100-400 Hz had a low field intensity ranging from 1.5 V/cm to 7.3 V/cm. Spectrophotometric and spectrofluorometric measurements were used to investigate the impact of these variables on cancer cell survival and the molecular probe uptake induced by the electric pulses. An all-or-nothing response was observed above a specified threshold of electric field intensity of 4 V/cm. This threshold was unaffected by changes in repetition frequency or pulse duration. It was not a temperature effect that caused the molecular probe uptake to increase. When bipolar asymmetric electric pulses were applied just before electroporation, the effectiveness of the cytotoxic impact of bleomycin was increased from 80%, when employing electroporation pulses alone, to 100%.

Keywords

• electroendocytosis
• asymmetric bipolar electrical impulses
• receptor-mediated endocytosis
• spectrofluorometry
• u251mg cells