Apoptosis-inducing effects of aqueous extract of Eleutherococcus senticosus on non-small cell lung cancer cell proliferation

Non-small cell lung cancer is a malignant tumor with high morbidity and mortality worldwide. Eleutherococcus senticosus can induce apoptosis in non-small cell lung cancer cells, but the mechanism remains unclear. This study aimed to elucidate the role of Eleutherococcus senticosus in inducing apoptosis in non-small cell lung cancer cells and analyze its potential active constituents, targets, and molecular mechanisms. The results of network pharmacology analysis showed that Eleutherococcus senticosus contained 49 active ingredients that induced apoptosis in non-small cell lung cancer cells, and these components could act on 66 apoptosis-related targets. Compared to the control group, Eleutherococcus senticosus significantly increased apoptosis in A549 cells with increasing concentration (p < 0.05). The results of transcriptome and metabolomic analyses showed that Eleutherococcus senticosus significantly changed 5836 genes and 418 metabolites in A549 cells (p < 0.05), with the most significant changes in 18 genes and 34 metabolites related to apoptosis. qRT-PCR and Western blot results showed that, after Eleutherococcus senticosus treatment, the mRNA and protein expression of EGFR, MAPK3, and ICAM1 significantly increased, while CTSK decreased (p < 0.01 or p < 0.001). Correlation analysis and molecular docking results indicated that calycanthoside and oleanolic acid can directly modify the expression levels of the transcription factors POU2F3, FOXS1, and TGIF2LY or indirectly influence the binding affinity of these transcription factors to the promoters of key target genes, ultimately leading to the activation of EGFR, MAPK3, ICAM1, and CTSK, which triggers apoptosis in non-small cell lung cancer cells.