Lycorine inhibits angiogenesis by docking to PDGFRα.
BMC Cancer
; 22(1): 873, 2022 Aug 10.
Article
em En
| MEDLINE
| ID: mdl-35948939
ABSTRACT
Lycorine (Lyc) is a natural alkaloid derived from medicinal plants of the Amaryllidaceae family. Lyc has been reported to inhibit the recurrence and metastasis of different kinds of tumors. However, Lyc's effect on angiogenesis and its specific mechanism are still not clear. This study was designed to test the antiangiogenesis effect of Lyc and to explore the possible mechanisms. We performed cell experiments to confirm Lyc's inhibitory effect on angiogenesis and employed sunitinib as a positive control. Moreover, the synergistic effect of Lyc and sunitinib was also explored. Next, we conducted bioinformatics analyses to predict the potential targets of Lyc and verified them by western blotting and immunofluorescence. Molecular docking, kinase activity assays, Biacore assays and cellular thermal shift assays (CETSAs) were applied to elucidate the mechanism by which Lyc inhibited target activity. Lyc inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs). Employing bioinformatics, we found that Lyc's target was PDGFRα and that Lyc attenuated PDGFRα phosphorylation. We also found that Lyc inhibited PDGFRα activation by docking to it to restrain its activity. Additionally, Lyc significantly inhibited PDGF-AA-induced angiogenesis. This study provides new insights into the molecular functions of Lyc and indicates its potential as a therapeutic agent for tumor angiogenesis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor alfa de Fator de Crescimento Derivado de Plaquetas
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
BMC Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China