Network Pharmacology, Molecular Docking, and Molecular Dynamics Studies to Predict the Molecular Mechanisms of Cyclocybe cylindracea Mushroom (Agaricomycetes) Active Compounds for the Treatment of Breast Cancer

The study aimed to elucidate the molecular mechanisms by which active compounds from the mushroom Cyclocybe cylindracea exert anti-breast cancer effects, using network pharmacology and computational simulation. We identified potential mushroom compounds from the literature for target protein prediction. Several online tools and databases were used to collect the data on mushroom ingredient-related targets and their potential breast cancer-related genetic targets. Protein-protein interaction (PPI) networks and pathway enrichment analyses were performed. Finally, molecular docking and dynamic simulations were used to validate the binding affinity of the compounds to their protein targets. As a result, five potential compounds were identified, corresponding to 440 predicted targets. PPI network revealed potential targets, including AKT1, TP53, MAPK1, ESR1, HSP90AA1, MAPK3, and TNF. Furthermore, the functional enrichment analysis showed that the core targets were mainly enriched in the microRNA cancer pathway, the MAPK pathway, and the PI3K/AKT signaling pathway. Molecular docking analysis demonstrated that the breast cancer-related targets AKT1, MAPK1, and MAPK3 exhibited stronger binding affinity with rosmarinic acid than the other selected compounds. Additionally, molecular dynamics simulation revealed good stability for the best MAPK1-rosmarinic acid complex. In conclusion, our findings suggest that the active compounds of C. cylindracea may have anticancer potential by interfering with multiple signaling pathways.