Uncovering the anti-cancer mechanism of cucurbitacin D against colorectal cancer through network pharmacology and molecular docking

Colorectal cancer is a significant global health challenge due to chemoresistance, necessitating new treatments. Cucurbitacin D, with its anti-cancer properties, shows promise, but its effects on colorectal cancer are not well understood. We investigated the impact of cucurbitacin D on colorectal cancer cell lines using MTT assays and Annexin V/7-AAD staining followed by flow cytometry for apoptosis analysis. Public databases helped identify cucurbitacin D and colorectal cancer-related gene targets for network pharmacology analysis. Protein-protein interaction networks were constructed using STRING and analyzed in Cytoscape. Gene ontology and KEGG pathway enrichment analyses were performed using ClueGo. Molecular docking studies were conducted via Autodock Vina and visualized in Discovery Studio. Western blot assessed protein expression changes in key targets under cucurbitacin D. Cucurbitacin D dose-dependently reduced colorectal cancer cell viability and induced apoptosis. Network pharmacology pinpointed crucial targets like STAT3, AKT1, CCND1, and CASP3. Molecular docking confirmed strong interactions with these targets. Enrichment analysis highlighted involvement in the 'PI3K-AKT,' 'JAK-STAT,' and 'ErbB' signaling pathways. These findings suggest cucurbitacin D as a potential anti-colorectal cancer agent, demonstrating significant effects on cell viability and apoptosis, and engaging critical cancer-related pathways, making it a promising candidate for further colorectal cancer therapeutic research.