The cytotoxic potential of sinapic acid on luminal A breast cancer; a computational and experimental pharmacology approach

Breast cancer is a highly concerning and prevalent disease that impacts a significant proportion of women worldwide, whose repeated exposure to therapies leads to resistance for drugs; making it alarming to identify novel chemotherapeutic agents. Sinapic acid is a phenolic acid that occurs naturally and is known to exhibit cytotoxic action in a variety of cancer cell types. In the present study, we utilized cell cytotoxicity assays to assess the cytotoxic potential of sinapic acid on various breast cancer subtypes. In addition, we assessed the cell migration rate, cell apoptosis, and cell cycle phases. Moreover, we utilized multiple system biology tools to predict the potential targets, and molecular docking was performed on the hub targets followed by molecular dynamic (MD) simulations. Cytotoxicity assay was performed on cell lines MCF7, T47D, MDA-MB-468, and SKBR3 at different time exposures of 24, 48, and 96 h. Our results revealed sinapic acid to be potent on MCF7 and T47D cell lines. The cell cycle analysis and cell apoptotic assays revealed sinapic acid to cause cell death by apoptosis majorly in the G0/G1 phase. Computational biology revealed <i>KIF18B</i> and <i>VKORC1</i> to possess the highest binding affinity of −6.5 and −7.5 kcal/mol; displayed stable trajectories on MD run. The cytotoxicity of sinapic acid on luminal A cell lines may be due to the modulation of <i>VKORC1</i> and <i>KIF18B</i> with major cell death in the G0/G1 phase. However, the mechanism has been proposed <i>via in silico</i> tools, which need further validation using wet lab protocols. Communicated by Ramaswamy H. Sarma