Berberine reverses epithelial-mesenchymal transition and modulates histone methylation in osteosarcoma cells.
Actin Cytoskeleton
/ drug effects
Berberine
/ pharmacology
Cadherins
/ genetics
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Epigenesis, Genetic
/ drug effects
Epithelial-Mesenchymal Transition
/ drug effects
Humans
Matrix Metalloproteinase 2
/ metabolism
Osteosarcoma
/ genetics
Proteolysis
/ drug effects
Vimentin
/ genetics
beta Catenin
/ genetics
Berberine
Epigenetic
Epithelial-mesenchymal transition
Histone methylation
Osteosarcoma
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
16
06
2020
accepted:
03
10
2020
pubmed:
20
10
2020
medline:
25
5
2021
entrez:
19
10
2020
Statut:
ppublish
Résumé
Osteosarcoma is the most frequently occurring cancer in children as well as young adolescents and the metastatic forms worsen this condition to a further great extent. The metastatic dissemination of cancer cells is often acquired through a process of epithelial-mesenchymal transition (EMT). Since, phytochemicals have attracted intense interest in recent years due to their diverse pharmacological effects, in the present study, we investigated if berberine, a naturally occurring isoquinoline quaternary alkaloid, could modulate the EMT in osteosarcoma cells. Our experimental studies showed that berberine reduced cell viability, colony formation, wound healing ability and migration of osteosarcoma cells. Also, berberine significantly reduced the expression of matrix metalloproteinase (MMP)-2, suggesting its inhibitory action on the matrix metalloproteinases that are required for cancer cell invasion. The significant reduction in the expression of vimentin, N-cadherin, fibronectin and increased expression of E-cadherin further suggested its role in the inhibition of EMT in osteosarcoma cells. The downregulation of H3K27me3, as well as the decreased expression of the histone methyl transferase enzyme EZH2, further substantiated the fact that the plant alkaloid can be used as an epigenetic modulator in the treatment of osteosarcoma. In conclusion, our findings suggest that berberine inhibits proliferation and migration of osteosarcoma cells and most importantly reverses EMT along with modulation of key epigenetic regulators.
Identifiants
pubmed: 33074411
doi: 10.1007/s11033-020-05892-8
pii: 10.1007/s11033-020-05892-8
doi:
Substances chimiques
Cadherins
0
Vimentin
0
beta Catenin
0
Berberine
0I8Y3P32UF
Matrix Metalloproteinase 2
EC 3.4.24.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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