Investigating the potential hub genes and mechanisms of Artemisia annua L. against breast cancer based on network pharmacology and molecular docking

Abstract

Artemisia annua L. has been revealed to possess antitumor effect in various human cancers. However, the mechanism of A. annua treating breast cancer (BRCA) has not been clearly elucidated. In present study, the bioactive compounds and mechanism of A. annua in the treatment of BRCA were explored based on network pharmacology and molecular docking. TCMSP database was used to predict the active components and components targets of A. annua. The targets of BRCA were collected through TTD, GeneCards, OMIM, PharmGKB and DisGeNET database. The analysis of GO and KEGG enrichment was conducted for intersection targets. Protein–Protein interaction (PPI) network was constructed using the STRING online database. Candidate core targets were screened using the gene expression analysis and survival analysis. Molecular docking analysis was conducted to verify whether the bioactive compounds had a definite affinity with candidate core targets. Finally, MTT and RT-qPCR experiments of MCF-7 cells and MDA-MB-231 cells were carried out to verify the results of network pharmacology.The quercetin, luteolin, kaempferol were selected as hub compounds of A. annua against BRCA. After the conduction of topological analysis, survival analysis, and gene expression analysis for the potential targets of A. annua against BRCA, 4 candidate hub targets (BICR5, CCNA2, E2F1 and FOS) were identified. Molecular docking results demonstrated that 3 hub components of A. annua had strong binding efficiency with the 4 candidate hub targets. The enrichment analysis of KEGG pathway revealed that A. annua exerted anti-BRCA effects via p53 signaling pathway, etc. After treated with total flavonoids of A. annua (ATF) for 48 h, mRNA expression levels of BICR5, CCNA2, E2F1 and FOS were significantly down-regulated in both MCF-7 cells and MDA-MB-231 cells. The present study reveals the mechanism of A. annua against BRCA through multiple targets, multiple ingredients and multiple signal pathways, and provides more references for its clinical application.