Network pharmacology integrated with experimental validation revealed potential molecular mechanisms of Camellia nitidissima C. W. Chi in the treatment of lung cancer

This study utilized network pharmacology analysis combined with experimental validation to identify the substance basis and potential molecular mechanism of CNC against lung cancer. Materials and

These results comprehensively clarified the associated substance basis and underlying molecular mechanism of CNC against lung cancer, which would be contributed to develop promising anti-cancer pharmaceuticals or therapeutic approaches for lung cancer therapy.

The active ingredients of CNC were identified based on published literature. The associated potential targets of CNC in lung cancer treatment were predicted using integrated network pharmacology analysis and molecular docking. The underlying molecular mechanism of CNC in lung cancer were validated in human lung cancer cell lines.

A total of 30 active ingredients and 53 targets of CNC were screened. An enrichment analysis of Gene Ontology (GO) revealed that the effects of CNC in lung cancer mainly involve protein binding, regulation of cell proliferation and apoptosis, and signal transduction. KEGG pathways analysis suggested that CNC might exert cancer suppression effects mainly through pathways in cancer, PI3K/AKT signaling pathway. Molecular docking revealed that CNC has high affinity for binding of EGFR, SRC, AKT1, and CCND1 to the key active ingredients including luteolin, kaempferol, quercetin, eriodictyol and 3'4-O-dimethylcedrusin. In in vitro experiments, CNC played the inhibitory roles in lung cancer cells by inducing cell apoptosis, causing G0/G1 and S cell cycle arrest, increasing intracellular ROS levels, and promoting the apoptotic proteins Bax and Caspase-3. Meanwhile, CNC also regulated the expression of core proteins EGFR, SRC, and AKT.