REPURPOSING METFORMIN WITH ELECTRICAL PULSES FOR TRIPLE-NEGATIVE BREAST CANCER APPLICATIONS: NOVEL IN-VITRO STUDIES

Triple Negative Breast Cancer (TNBC) is an aberrant type of breast cancer subset that lacks traditional biomarkers (e.g., estrogen receptor (ER), progesterone receptor (PR)) and shows no upregulation in HER2 protein (human epidermal growth factor receptor 2). It is particularly aggressive due to the absence of three key receptors (ER, PR, and HER2 protein), resulting in limited treatment options and a higher risk of metastasis, recurrence, and mortality. Thus, there is a need for alternative therapies. Towards this, we studied the antiproliferation characteristics of electrical pulse-mediated therapy using Metformin, a commonly used Type-2 diabetes drug, alone and in combination with Cisplatin. This research demonstrates the novel repurposing of

Metformin, an affordable, FDA-approved, and widely used anti-diabetic drug, on MDA-MB-231 and MDA-MB-468 human TNBC cells. For the first time, we explore the impact of combining Metformin with electrical pulses (EP+Met) on these aggressive cell lines, optimizing electrical parameters and utilizing key in-vitro cell viability and metabolic assays. Our study integrates high-throughput, label-free quantitative proteomics, cell viability, and ROS analysis alongside advanced computational tools, such as Cytoscape (STRING) protein-protein interaction, GOrilla, and KEGG pathway analysis, to identify and analyze differentially expressed proteins, ensuring robust and reliable insights.