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

Camellia nitidissima C.W.Chi (CNC), an ethnomedicine mainly distributed in Southern China's Guangxi Zhuang Autonomous Region, is known as “Panda in plants” and “Camellias Queen” due to its golden blossom. CNC has been applied as a traditional folk medicine in cancer therapy. This study utilized network pharmacology analysis combined with experimental validation to identify the substance basis and potential molecular mechanism of CNC against lung cancer. 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. 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. Workflow to study the molecular mechanism of CNC for the treatment of lung cancer. [Display omitted] •Network pharmacology analysis was applied to identify CNC treatment on lung cancer.•CNC inhibits lung cancer via multi-ingredients, multitargets and multi-pathways.•The key active ingredients of CNC exhibit high affinity with the potential targets.•CNC inhibits the proliferation of A549 and SK-MES-1 and promotes cell apoptosis and cycle arrest.•CNC promotes lung cell apoptosis and cell cycle arrest.•CNC