Bruceine A induces apoptosis of non-small cell lung cancer cells by EMT signaling axis
- VernacularTitle:鸦胆子素A通过EMT信号诱导非小细胞肺癌细胞凋亡
- Author:
Dan-bei WU DI
1
;
Hong WANG
;
Hong-Yan TAO
;
Fan-Qi WU
Author Information
- Keywords: bruceine A; non-small cell lung cancer; epithelial mesenchymal transition; apoptosis; target prediction; molecular docking
- From: Chinese Pharmacological Bulletin 2024;40(8):1474-1481
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of bruceine A on apoptosis and invasion of non-small cell lung cancer(NSCLC)cells and to explore its possible molecular mechanism.Methods CCK-8 and cell colony assay were used to detect the effect of bruceine A on prolifer-ation and clone formation ability of NSCLC cells.3D matrigel drop invasion assay and flow cytometry were used to detect cell invasion ability and apoptosis rate.Western blot was used to detect expressions of epitheli-al-mesenchymal transition(EMT)key proteins and ap-optosis key proteins.The anti-tumor effect of bruceine A was detected on A549 xenograft mice in vivo.Online databases,molecular docking methods and drug affinity responsive target stability(DARTS)were used to pre-dict and screen the potential binding targets of bruceine A.Results Bruceine A significantly inhibited the proliferation and colony formation of NSCLC cells.Bruceine A significantly induced the apoptosis in NSCLC cells and inhibited cell invasion ability,signifi-cantly up-regulated the protein expressions of c-caspase3,c-PARP,Bax and E-cadherin,and signifi-cantly down-regulated the protein expressions of Bcl-2,N-cadherin,Vimentin and Snail(P＜0.05).In the tumor-bearing mouse models,bruceine A significantly decreased the tumor volume and tumor weight(P＜0.05).Target prediction,molecular docking and Western blot analysis of DARTS sample revealed that bruceine A could increase the stabilization of HSP90α.Conclusions Bruceine A reduces the EMT levels and induces apoptosis in NSCLC cells through the EMT signaling axis.Bruceine A may exert its anti-cancer effect by binding to HSP90α.
