Revealing the action mechanisms of scutellarin against glioblastoma based on network pharmacology and experimental validation

• Autor(a) principal: SUN,Junzhao
• Data de Publicação: 2022
• Outros Autores: WANG,Hongwei, CHENG,Gang, ZHANG,Leiming, QU,Zhifeng, HAN,Chengchen, ZHENG,Wei, WU,Lin, ZHANG,Jianning
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Food Science and Technology (Campinas)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0101-20612022000100914
• topic: network pharmacology; scutellarin; glioblastoma; EGFR-PI3K-AKT

Abstract Scutellarin, a flavonoid compound found in Scutellaria barbata, has been demonstrated to exert anti-cancer properity in a variety of human malignancies. However, its biological significance and underlying mechanism in glioblastoma (GBM) remain ambiguous. Network pharmacology approaches and molecular docking technologies were used to predict the crucial biological processes, candidate targets and signaling pathways of scutellarin against GBM. CCK-8, EdU, and colony formation experiments were performed to determine the effects of scutellarin on cell proliferation. Flow cytometry analysis was utilized to detect apoptosis. Western blot assays were used to measure the expression of proteins associated with EGFR-PI3K-AKT signaling. Through network pharmacology and molecular docking analysis, we found that EGFR might be a potential target and PI3K-AKT signaling might be the key signaling pathway for scutellarin to combat GBM. Scutellarin inhibited cell proliferation and induced apoptosis in a dose-dependent manner. Scutellarin also suppressed the phosphorylation level of EGFR in a dose-dependent manner. Scutellarin inactivated PI3K-AKT signaling by targeting EGFR. Moreover, scutellarin-mediated suppression of cell proliferation and increase of apoptosis was greatly reversed in GBM after overexpressing EGFR. Taken together, scutellarin is a novel inhibitor of EGFR-PI3K-AKT signaling to prevent GBM progression.