Quantitative Proteomic Assessment of Key Proteins Regulated by Electrical Pulse-mediated Galloflavin Delivery in Triple-Negative Breast Cancer Cells

Abstract

Triple-negative breast cancer (TNBC) is the most lethal subset of breast cancers, lacking targeted therapies. There is a critical need to identify alternative treatments for TNBC. Towards this, in this research, we investigated the anticancer effects of Galloflavin (GF), an LDHB inhibitor, in reducing the proliferation of MDA-MB-231, the human triple-negative breast cancer cells. To enhance the uptake of GF, we applied electrical pulses (EP) with GF and studied its protein profile characteristics and viability. We used GF at a concentration of 100μM with 800V/cm, 100μs, and eight electrical pulses to treat these cells. Label-free, high throughput, quantitative proteomics results indicated that 172 proteins were significantly downregulated, while 222 proteins were significantly upregulated. The upregulated proteins include Cytochrome C Oxidase Assembly Factor and Mitochondrial Ribosomal proteins. Key downregulated proteins include LDHB, and ENO1 in EP+GF treatments, compared to GF only, indicating the effect of EP+GF combination in reducing the proliferation of the TNBC cells. These results pave the path for additional therapy for TNBC and the various pathways the TNBC cells proceeded with Electrochemotherapy.