Investigate the mechanisms of novel verticinone derivatives on lung cancer cell line (A549) by network pharmacology and transcriptome.

Bulb of Fritillaria ( Bèi Mǔ) has been wildly used in Chinese medicine for serval centuries since its significant therapeutic effects on respiratory diseases, such as cough, expectoration, pneumonia, and bronchial inflammation. Verticinone is the main active ingredient in bulbs of Fritillaria. The novel verticinone derivatives are synthesized by verticinone and different bile acids and showed promising anti-lung cancer properties. This study aims to compare the ability of three novel verticinone derivatives (HDCA-Ver, CDCA-Ver and DCA-Ver) inhibiting A549 and MDA-MB-231 cells proliferation in vitro, and to investigate the inhibiting mechanism of CDCA-Ver on lung cancer. CCK-8 observed the effect of CDCA-Ver, DCA-Ver and HDCA-Ver on A549 and MDA-MB-231 cells. Annexin-FITC/PI double, Hoechst 33258, and PI staining were used to evaluate the ability of CDCA-Ver inducing A549 cells apoptosis. Network pharmacology and transcriptomics were also performed to further analyze the molecular mechanisms of CDCA-Ver therapy for lung cancer. We found that CDCA-Ver, DCA-Ver and HDCA-Ver could significantly inhibit A549 and MDA-MB-231 cells proliferation. CDCA-Ver could significantly induce A549 cells apoptosis and G0/G1 cell cycle arrest. Network pharmacology demonstrates that the potential targets of CDCA-Ver mainly include "EGFR tyrosine kinase inhibitor resistance". According to transcriptome analysis, CDCA-Ver mainly activated "Metabolic pathways" and "Cell cycle" targets. This study could provide scientific basis for the application of CDCA-Ver.