Exploring the Mechanism of Brucea Javanica against Ovarian Cancer based on Network Pharmacology and the Influence of Luteolin on the PI3K/AKT Pathway.
AKT
Brucea javanica
Core targets
Luteolin
Molecular docking
Network pharmacology
Ovarian cancer
PI3K
Journal
Combinatorial chemistry & high throughput screening
ISSN: 1875-5402
Titre abrégé: Comb Chem High Throughput Screen
Pays: United Arab Emirates
ID NLM: 9810948
Informations de publication
Date de publication:
27 Jun 2023
27 Jun 2023
Historique:
received:
05
05
2023
revised:
18
06
2023
accepted:
21
06
2023
medline:
27
6
2023
pubmed:
27
6
2023
entrez:
27
6
2023
Statut:
aheadofprint
Résumé
Ovarian cancer (OC) is a commonly diagnosed female cancer around the world. The Chinese herbal medicine Brucea javanica has an anti-cancer effect. However, there is no relevant report on whether Brucea javanica is effective in treating OC, and the corresponding mechanism is also unknown. This study was projected to excavate the active components and underpinned molecular mechanisms of Brucea javanica in treating ovarian cancer (OC) through network pharmacology combined with in vitro experiments. The essential active components of Brucea javanica were selected using the TCMSP database. The OC-related targets were selected by GeneCards, intersecting targets were obtained by Venn Diagram. The core targets were obtained through the PPI network and Cytoscape, and the key pathway was gained through GO and KEGG enrichment analyses. Meanwhile, docking conformation was observed as reflected by molecular docking. MTT, colony formation assay and flow cytometer (FCM) analysis were performed to determine cell proliferation and apoptosis, respectively. Finally, Levels of various signaling proteins were evaluated by western blotting. Luteolin, β-sitosterol and their corresponding targets were selected as the essential active components of Brucea javanica. 76 intersecting targets were obtained by Venn Diagram. TP53, AKT1, and TNF were obtained through the PPI network and Cytoscape, and the key pathway PI3K/AKT was gained through GO and KEGG enrichment analyses. A good docking conformation was observed between luteolin and AKT1. Luteolin could hinder A2780 cell proliferation, induce cell apoptosis and enhance the inhibition of the PI3K/AKT pathway. It was verified in vitro that luteolin could hinder OC cell proliferation and activate the PI3K/AKT pathway to lead to apoptosis.
Sections du résumé
BACKGROUND
BACKGROUND
Ovarian cancer (OC) is a commonly diagnosed female cancer around the world. The Chinese herbal medicine Brucea javanica has an anti-cancer effect. However, there is no relevant report on whether Brucea javanica is effective in treating OC, and the corresponding mechanism is also unknown.
OBJECTIVE
OBJECTIVE
This study was projected to excavate the active components and underpinned molecular mechanisms of Brucea javanica in treating ovarian cancer (OC) through network pharmacology combined with in vitro experiments.
METHODS
METHODS
The essential active components of Brucea javanica were selected using the TCMSP database. The OC-related targets were selected by GeneCards, intersecting targets were obtained by Venn Diagram. The core targets were obtained through the PPI network and Cytoscape, and the key pathway was gained through GO and KEGG enrichment analyses. Meanwhile, docking conformation was observed as reflected by molecular docking. MTT, colony formation assay and flow cytometer (FCM) analysis were performed to determine cell proliferation and apoptosis, respectively. Finally, Levels of various signaling proteins were evaluated by western blotting.
RESULTS
RESULTS
Luteolin, β-sitosterol and their corresponding targets were selected as the essential active components of Brucea javanica. 76 intersecting targets were obtained by Venn Diagram. TP53, AKT1, and TNF were obtained through the PPI network and Cytoscape, and the key pathway PI3K/AKT was gained through GO and KEGG enrichment analyses. A good docking conformation was observed between luteolin and AKT1. Luteolin could hinder A2780 cell proliferation, induce cell apoptosis and enhance the inhibition of the PI3K/AKT pathway.
CONCLUSION
CONCLUSIONS
It was verified in vitro that luteolin could hinder OC cell proliferation and activate the PI3K/AKT pathway to lead to apoptosis.
Identifiants
pubmed: 37366364
pii: CCHTS-EPUB-132704
doi: 10.2174/1386207326666230627114111
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.