Stearyl palmitate a multi-target inhibitor against breast cancer: in-silico, in-vitro & in-vivo approach

Multi-target inhibitors are currently trending in the pharmaceutical research, as they possess increased efficacy and reduced toxicity. In this study multi-target inhibitors for breast cancer are explored from a curated list of natural products, i.e. 4,670 phytochemicals belonging to 360 medicinal plants. In-silico screening of phytochemicals using SeeSAR and AutoDock Vina resulted in identification of Stearyl Palmitate as a potential drug molecule that inhibits three drug targets, i.e. HER-2, MEK-1 and PARP-1 proteins. Molecular Dynamics Simulation for 100 ns each for these three protein-ligand complexes using Desmond, Maestro platform also confirmed the prediction of multi-target inhibition by Stearyl Palmitate. Further in-vitro MTT assay demonstrated that Stearyl Palmitate has a significant IC50 value of 40 mM against MCF-7 cells and >1000 mM against L929 cells. This confirmed that Stearyl Palmitate is having selective cytotoxicity towards breast cancer cells in comparison to non-cancerous cells. Fluorescence staining and flow cytometry analysis confirmed that, Stearyl Palmitate is inducing apoptosis in MCF-7 cells at IC50 concentration. Finally, in-vivo efficacy and toxicity studies were performed using zebrafishes (Danio rerio). It was observed that the fishes treated with IC50 concentration of Stearyl Palmitate demonstrated 2x folds reduction in tumour size, while double dose resulted in 4x folds reduction in tumour size. Stearyl Palmitate did not demonstrate any toxicity or side effects in the zebrafishes. It is concluded that, Stearyl Palmitate, a phytochemical reported to be present in Althea officinalis is a potential anti-breast cancer agent, with ability to inhibit multiple targets such as HER-2, MEK-1 and PARP-2 proteins.