Luteolin inhibits A549 cells proliferation and migration by down-regulating androgen receptors.
A549 cancer cells
Androgen receptor
Luteolin
Yi Fei Qing Hua Granules
Journal
European journal of medical research
ISSN: 2047-783X
Titre abrégé: Eur J Med Res
Pays: England
ID NLM: 9517857
Informations de publication
Date de publication:
16 Sep 2023
16 Sep 2023
Historique:
received:
05
05
2023
accepted:
18
08
2023
medline:
18
9
2023
pubmed:
17
9
2023
entrez:
16
9
2023
Statut:
epublish
Résumé
Yi Fei Qing Hua Granules (YQG) is a traditional Chinese herbal medicine with the effects of inhibiting the proliferation of lung cancer cells. Luteolin is one of the active compounds of YQG. Luteolin is a common flavonoid extracted from natural herbs and it can promote cancer cells apoptosis has been reported. However, the underlying molecular mechanism and effects of luteolin on human lung cancer needs to be validated. Molecular docking, network pharmacology methods and quantitative structure-activity relationship (QSAR) model were used to identify the active components of YQG and their possible mechanisms of action. Western blot analysis was used to measure AR expression in A549 cells. Cell migration assays were used to detect A549 cells proliferation transfected by AR plasmid and AR mutation plasmid, respectively. TCMSP search results revealed that there are 182 active compounds in YQG, which correspond to 232 target genes. Sixty-one genes were overlapping genes in the 2 datasets of TCMSP and GeneCards. Through bioinformatics tagging of these overlapping genes, a total of 1,951 GO functional tagging analysis and 133 KEGG pathways were obtained. Through molecular docking technology and QSAR model verification, the multi-target active compound luteolin was screened out as one of the active components of YQG for in vitro verification. Androgen receptor (AR) was the hub protein with the highest docking score of luteolin. Western blot showed that luteolin could inhibit AR protein expression in lung cancer cell line A549. After the phosphorylation site of AR protein 877 was inactivated, the ability of luteolin to inhibit the proliferation of lung cancer cells was weakened. Luteolin significantly inhibited the growth of A549 xenogeneic tumors at day 25 and 28 and inhibited the expression of AR. In this study, we have explored luteolin as one of the active components of YQG, and may inhibit the proliferation and migration of A549 cells by decreasing the expression of AR and the regulation of phosphorylation at AR-binding sites.
Sections du résumé
BACKGROUND
BACKGROUND
Yi Fei Qing Hua Granules (YQG) is a traditional Chinese herbal medicine with the effects of inhibiting the proliferation of lung cancer cells. Luteolin is one of the active compounds of YQG. Luteolin is a common flavonoid extracted from natural herbs and it can promote cancer cells apoptosis has been reported. However, the underlying molecular mechanism and effects of luteolin on human lung cancer needs to be validated.
METHODS
METHODS
Molecular docking, network pharmacology methods and quantitative structure-activity relationship (QSAR) model were used to identify the active components of YQG and their possible mechanisms of action. Western blot analysis was used to measure AR expression in A549 cells. Cell migration assays were used to detect A549 cells proliferation transfected by AR plasmid and AR mutation plasmid, respectively.
RESULTS
RESULTS
TCMSP search results revealed that there are 182 active compounds in YQG, which correspond to 232 target genes. Sixty-one genes were overlapping genes in the 2 datasets of TCMSP and GeneCards. Through bioinformatics tagging of these overlapping genes, a total of 1,951 GO functional tagging analysis and 133 KEGG pathways were obtained. Through molecular docking technology and QSAR model verification, the multi-target active compound luteolin was screened out as one of the active components of YQG for in vitro verification. Androgen receptor (AR) was the hub protein with the highest docking score of luteolin. Western blot showed that luteolin could inhibit AR protein expression in lung cancer cell line A549. After the phosphorylation site of AR protein 877 was inactivated, the ability of luteolin to inhibit the proliferation of lung cancer cells was weakened. Luteolin significantly inhibited the growth of A549 xenogeneic tumors at day 25 and 28 and inhibited the expression of AR.
CONCLUSION
CONCLUSIONS
In this study, we have explored luteolin as one of the active components of YQG, and may inhibit the proliferation and migration of A549 cells by decreasing the expression of AR and the regulation of phosphorylation at AR-binding sites.
Identifiants
pubmed: 37716981
doi: 10.1186/s40001-023-01302-4
pii: 10.1186/s40001-023-01302-4
pmc: PMC10504720
doi:
Substances chimiques
Receptors, Androgen
0
Luteolin
KUX1ZNC9J2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
353Subventions
Organisme : the Natural Science Research Project of Jiading District, Shanghai
ID : JDKW-2021-0035
Organisme : the Health System of Jiading District, Shanghai
ID : 2019JDJYXX010
Organisme : the National Natural Science Foundation of China
ID : 81773157
Organisme : the Key Program of National Natural Science Foundation of China
ID : 81830052
Organisme : the Construction project of the Shanghai Key Laboratory of Molecular Imaging
ID : 18DZ2260400
Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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