Analysis of Pathways in Triple-Negative Breast Cancer Cells Treated with the Combination of Electrochemotherapy and Cisplatin

More than 2 million new cases and over 600,000 breast cancer deaths were reported in 2018 worldwide. Out of these, 15 to 20% are Triple Negative Breast Cancer (TNBC), which lack all the three most commonly administered receptors, namely ER, PR, and Her2 amplification. Hence, TNBC is difficult to treat; and it has the highest five-year recurrence rate among breast cancer types. Currently, TNBC patients are treated with platinum-based chemotherapeutics, such as cisplatin. With the aggressive and metastatic nature of TNBC cells, it demands immediate, alternate treatments. Electrochemotherapy is a proven drug delivery practice in molecular medicine. The combination of electrical pulses (EP)with Cisplatin (CsP)is studied using Label-free quantitative proteomics to better understand action pathways. Cisplatin alone and cisplatin combined with Electroporation (EP+CsP) on MDA-MB-231, human TNBC cells were used for this purpose. The results indicate that EP + CsP significantly upregulated Mitochondrial ribosomes and significantly downregulated ribosomes and ubiquitin-mediated proteolysis. A total of 12 proteins were found downregulated among both ribosomes and ubiquitin-mediated proteolysis. A total of 29 proteins were upregulated among Ribosomes. Mitochondrial ribosomes upregulation indicates the DNA damage was done by cisplatin, and proteasome inhibitors are proven to function as novel anticancer compounds.