System biology mediated assessment of molecular mechanism for sinapic acid against breast cancer: via network pharmacology and molecular dynamic simulation

Abstract

Sinapic acid is a hydroxycinnamic acid widespread in the plant kingdom, known to be a potent anti-oxidant used for the treatment of cancer, infections, oxidative stress, and inflammation. However, the mode of action for its chemotherapeutic properties has yet not been unleashed. Hence, we aimed to identify potential targets to propose a possible molecular mechanism for sinapic acid against breast cancer. We utilized multiple system biology tools and databases like DisGeNET, DIGEP-Pred, Cytoscape, STRING, AutoDock 4.2, AutoDock vina, Schrodinger, and gromacs to predict a probable molecular mechanism for sinapic acid against breast cancer. Targets for the disease breast cancer, were identified via DisGeNET database which were further matched with proteins predicted to be modulated by sinapic acid. In addition, KEGG pathway analysis was used to identify pathways; a protein-pathway network was constructed via Cytoscape. Molecular docking was performed using three different algorithms followed by molecular dynamic simulations and MMPBSA analysis. Moreover, cluster analysis and gene ontology (GO) analysis were performed. A total of 6776 targets were identified for breast cancer; 95.38% of genes predicted to be modulated by sinapic acid were common with genes of breast cancer. The ‘Pathways in cancer’ was predicted to be modulated by most umber of proteins. Further, PRKCA, CASP8, and CTNNB1 were predicted to be the top 3 hub genes. In addition, molecular docking studies revealed CYP3A4, CYP1A1, and SIRT1 to be the lead proteins identified from AutoDock 4.2, AutoDock Vina, and Schrodinger suite Glide respectively. Molecular dynamic simulation and MMPBSA were performed for the complex of sinapic acid with above mentioned proteins which revealed a stable complex throughout simulation. The predictions revealed that the mechanism of sinapic acid in breast cancer may be due to regulation of multiple proteins like CTNNB1, PRKCA, CASP8, SIRT1, and cytochrome enzymes (CYP1A1 & CYP3A4); the majorly regulated pathway was predicted to be ‘Pathways in cancer’. This indicates the rationale for sinapic acid to be used in the treatment of breast cancer. However, these are predictions and need to be validated and looked upon in-depth to confirm the exact mechanism of sinapic acid in the treatment of breast cancer; this is future scope as well as a drawback of the current study.