Cytochalasin D as a potential MAPK family inhibitor for treating triple-negative breast cancer

Cytochalasin D, a potent fungal metabolite, has garnered considerable attention due to its diverse biological activities and potential pharmacological applications. Renowned for its ability to disrupt actin polymerisation, it has been extensively used to elucidate cytoskeletal mechanisms. Alongside, it has also earned interest as a cytotoxic agent in cancer therapy. In the current study, we have employed network pharmacology to identify the specific molecular targets in TNBC. Protein targets of cytochalasin D and related drugs (&gt;0.5 similarity score) were obtained from multiple databases. An intricate network was constructed using Cytoscape software highlighting the extensive interplay between the drugs and protein targets. Further analysis of the network revealed six proteins with high significance in cancer cell progression. Molecular docking and MD simulation data showed stable complexes of cytochalasin D when paired with the members of MAPK family. The findings were confirmed <i>in vitro</i> by western blot analysis. A reduction in protein expression was observed in case of all the four MAPKs making it safe to say that cytochalasin D is very likely an inhibitor of the MAPK family proteins, hence giving an insight about the molecular mechanism of the drug as a chemotherapeutic agent.