High Intensity Microsecond-Electric Pulses Modulate Cell Death in MDA-MB-231 Cells Treated with Resveratrol

In this study, we investigated the potential of high-intensity microsecond electrical pulses (EPs) to augment intracellular delivery and enhanced uptake of Resveratrol (Resv), a natural polyphenol, as a novel therapeutic agent in the treatment of Triple Negative Breast Cancer (TNBC). For this purpose, MDA-MB-231, human TNBC cells were used. Resv exhibits potent anticancer properties, including the inhibition of tumor initiation, promotion, and progression, by modulating key molecular pathways involved in cell growth and apoptosis. Its multifaceted mechanisms of action make it a promising anticancer agent, especially for TNBC, characterized for its aggressive nature and high mortality rates, posing significant challenges in oncology. Conventional treatment modalities often are refractive, due to the absence of the most common hormone receptors, leading to increased recurrence and metastasis. Our approach leverages the bioelectrical modulation capacity of EPs to transiently permeabilize the TNBC cell membranes, thereby enhancing the uptake of Resv, a natural compound with limited bioavailability. Utilizing the MDA-MB-231 TNBC cell line, the impact of varying EP parameters (8 pulses at electric field of 2500 V/cm to 5000 V/cm, 10µs, 1 Hz) on cell viability and intracellular reactive oxygen species (ROS) were explored. Results indicated cell survival, as low as 11%, at 48 h with 5000 V/cm pulses, while it was 15% for 2500 V/cm (control at 100%). The ROS levels were enhanced to 350% (control at 100%). The consequent apoptotic activity due to ROS underscore the potential of this novel bioelectrical modulation technique in improving the outcomes of TNBC treatments. This research contributes to the emerging field of electrical pulse modulation in enhanced drug delivery and offers a promising avenue for addressing the limitations of current TNBC therapeutic strategies.