Brusatol induces apoptosis in small cell lung cancer by inhibiting STAT3 phosphorylation
10.12360/CPB202504055
- VernacularTitle:鸦胆子苦醇抑制STAT3磷酸化诱导小细胞肺癌凋亡
- Author:
Hui-lan WEI
1
;
Xin-yu WEI
1
;
Mu-zi JIANG
1
;
Shan-shan WEI
1
;
Zhuo LUO
1
;
Jie YANG
1
Author Information
1. 广西医科大学药学院,广西南宁 530021
- Publication Type:Journal Article
- Keywords:
Brusatol;
small cell lung cancer;
apopto-sis;
STAT3;
network pharmacology;
molecular docking
- From:
Chinese Pharmacological Bulletin
2025;41(10):1940-1947
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effect of Brusatol a-gainst small cell lung cancer(SCLC)and its potential mechanism.Methods CCK-8 assay and flow cytome-try were used to detect the cytotoxic effect of Brusatol on SCLC cells.Western blot was employed to measure the expression levels of apoptosis-related proteins,in-cluding cleaved poly(ADP-ribose)polymerase(cleaved-PARP),B-cell lymphoma 2(Bcl-2)and Bcl-2-associated X protein(Bax).Network pharma-cology databases were utilized to identify common tar-gets of Brusatol,SCLC,and apoptosis.Kyoto Encyclo-pedia of Genes and Genomes(KEGG)and Gene On-tology(GO)enrichment analyses were performed on the intersecting genes.Molecular docking simulations between Brusatol and core targets were conducted using the CB-DOCK2 online platform to calculate binding en-ergies and sites.Western blot was further applied to detect the expression levels of signal transducer and ac-tivator of transcription 3(STAT3)and phosphorylated-STAT3(p-STAT3).Results Brusatol inhibited SCLC cell growth and induced apoptosis,significantly downregulating Bcl-2 and cleaved-PARP while upregu-lating Bax expression(P＜0.05).Network pharma-cology analysis revealed 108 common targets of Brusa-tol and SCLC,with the top three core targets being ep-idermal growth factor receptor(EGFR),STAT3,and tumor necrosis factor(TNF).Molecular docking re-sults indicated strong binding affinity between bruceine D and these core targets.Western blot validation con-firmed that bruceine D suppressed the expression of STAT3 and p-STAT3.Conclusion Brusatol exerts anti-SCLC effects by inhibiting STAT3 to induce apop-tosis in SCLC cells.
