Optimization of electrode material and geometry to enhance TTFields-like anticancer effects in MCF-7 breast cancer cells

Abstract

Abstract Breast cancer is the most frequently diagnosed malignancy and a leading cause of cancer-related mortality among women worldwide. Tumor treating fields (TTFields) are a non-invasive anticancer modality based on low-intensity, intermediate-frequency alternating electric fields. In the present study, a conductive electrode-based TTFields-like in vitro exposure system was used to investigate how electrode material and geometry influence biological responses in breast cancer cells. Specifically, we examined the effects of electrode material (silver, gold, and stainless steel), surface area (0.5 and 1 cm 2 ), and number of electrodes (two or four) on the response of human breast cancer cells (MCF-7) to TTFields-like exposure generated using conductive metallic electrodes (150 kHz, 2 V/cm). Cells were exposed once for 15 min using conductive plate electrodes in direct contact with the culture medium. Treatment outcomes were assessed using flow cytometric analysis of cell viability and apoptosis, quantitative PCR analysis of apoptotic regulators, measurement of total antioxidant capacity (TAC), and inductively coupled plasma mass spectrometry (ICP-MS) to quantify metal ion accumulation. Increasing electrode surface area produced a greater reduction in viable tumor cells than increasing electrode number across all materials. Silver electrodes induced the strongest cytotoxic and apoptotic effects, accompanied by a significant increase in the BAX/BCL-2 ratio, indicating activation of the mitochondrial apoptotic pathway. Notably, silver electrodes caused smaller reductions in TAC compared with gold and stainless-steel electrodes under equivalent conditions, despite detectable metal ion accumulation. These findings demonstrate that electrode material and surface area are critical determinants of cellular response to TTFields-like exposure, highlighting a balance between anticancer efficacy and oxidative stress in vitro.