In silico Identification of Differentially Expressed Genes in Triple Negative Breast Cancer and Evaluation of Anticancer Mechanism and Modulation of Gene Expression by Degalactotigonin in MDA MB 231 Cell line

Abstract

Triple-negative breast cancer (TNBC) is a complex and heterogeneous disease newlinecharacterized by the lack of three characteristic receptors: human epidermal growth factor newlinereceptor 2, estrogen receptor, and progesterone receptor. Compared with other breast newlinecancer subtypes, TNBC tends to be more aggressive, have a higher prevalence, and newlineaffect young women. Currently, TNBC has no clinically accepted tailor-made therapeutic newlinetargets and candidate biomarker-ready targets are needed. In this study, integrated newlinebioinformatics and in vitro studies were performed to discover key candidate genes newlinespecific to TNBC. This study was conducted in four different phases. Phase I of the study newlineused an in silico approach to compare the gene expression profiles of normal and triplenegative newlinebreast cancer samples. This was accomplished by comparing TNBC gene newlineexpression profiles to paired normal gene expression profiles from the gene expression newlineomnibus and to look for upregulated and down regulated genes. Further molecular newlinedocking studies assisted us in identifying the key genes that would interact with the newlinecompound Degalactotigonin by modulating genes involved in the cell cycle, apoptosis, newlineand cancer progression pathways. newlineIn phase II of the study, we attempted to investigate anticancer mechanism, antiproliferative, newlineand anti-metastatic effect of Degalactotigonin in Triple Negative Breast newlineCancer cell line (MDA MB 231) and compared with the standard chemotherapeutic drug newlineEtoposide. The results of phase II confirmed that degalactotigonin can suppress cell newlineproliferation and migration of MDA-MB-231 cells, and it was clear from the results that newlinedegalactotigonin and etoposide synergistically inhibited cell growth in MDA-MB-231 cells newlinemore efficiently than either alone. In phase III of the study, we assessed various newlineparameters to determine the mode of cell death caused by the synergistic effect of newlinedegalactotigonin and etoposide. It induced cell death via apoptosis, which was triggered newlineby ROS.