Fluorinated chalcone arrests cell cycle progression in Triple-Negative Breast Cancer Cells by decreasing the expression of cyclin A, cyclin B1 and Cdc 2 protein

Abstract

Introduction: triple negative breast cancer (TNBC) represents around 20 % of all cases of breast cancer worldwide, being one of the most aggressive cancers, as it is are associated with advanced tumor grades, as well as with several alterations in the expression of genes involved in the regulation of cell proliferation and survival. Chalcones [(1,3-diaryl)-2-propen-1-one] are valuable organic compounds for drug development, which have shown anti-cancer activity against various tumor cells, including breast cancer, due to the fact that they modulate gene expression in various mechanisms associated with cell growth and proliferation. Objective. To identify genes that could be involved with the anti-cancer effect of fluorinated chalcone, using the MDA-MB-231 cell line as a model of this condition. Methodology. We synthesized the chalcone derivative (E)-3-(4-fluorophenyl)-1-(2-pyrazinyl)-prop-2-en-1-one, by the Claisen-Schmidt condensation method. Then, using a Next-Generation Sequencing (NGS) approach, we compared the transcriptomes of MDA-MB-231 cells treated vs. untreated, in order to identify the genes involved with the anti-cancer effect of fluorinated chalcone. Results. We found that this compound downregulates several target genes involved in the cell cycle progression, including: cyclin A, cyclin B1 and Cdc2 genes, in addition to increasing the genes expression that regulate this mechanism, such as: p21 and p27. Conclusion. This research indicates that fluorinated chalcone arrests cell cycle progression by regulating important genes involved in this mechanism.