Identification of molecular targets of Trigonelline for treating breast cancer through network pharmacology and bioinformatics-based prediction.

Breast cancer, a highly prevalent and fatal cancer that affects the female population worldwide, stands as a significant health challenge. Despite the abundance of chemotherapy drugs, the adverse side effects associated with them have initiated an investigation into natural plant-based compounds. Trigonelline, an alkaloid found in Trigonella foenum-graecum, was previously reported for its anticancer properties by the researchers. In this present study, we have identified the molecular targets of Trigonelline in breast cancer and predicted its drug-like properties and toxicity. By analyzing breast cancer targets from databases including TTD, TCGA, Gene cards, and Trigonelline targets obtained from CTD, we identified 14 specific targets of Trigonelline in the context of breast cancer. The protein-protein interaction (PPI) network of the 14 Trigonelline targets provided insights into the complex relationships between different genes and targets. Heatmap analysis demonstrated the expression patterns of these 14 genes at the protein and RNA levels in breast cancer cells and breast tissues. Notably, four genes, namely EGF, BAX, EGFR, and MTOR, were enriched in the breast cancer pathway. At the same time, PARP1, DDIT3, BAX, and TNF were associated with the apoptosis pathway according to KEGG pathway enrichment analyses. Molecular docking studies between Trigonelline and target proteins from the Protein Data Bank (PDB) revealed favorable binding affinity. Furthermore, mutation analysis of target genes within a dataset of 1918 samples from cBioPortal revealed the absence of mutations. Remarkably, Trigonelline also exhibited binding affinity towards two mutant proteins, and based on these findings, we predicted that Trigonelline could be utilized to target breast cancer genes and their mutants through network pharmacology. Additionally, this was supported by molecular dynamic simulation studies. As our study is preliminary, further validation through in vitro and in vivo studies is essential to confirm the efficacy of Trigonelline in breast cancer treatment.