Sorbaria sorbifolia flavonoid derivative induces mitochondrial apoptosis in human hepatoma cells through Bclaf1

Autor: Jiaxin Chen, Haoyi Cheng, Chunhua Bai, Dandan Wang, Jinghao Fu, Jinge Hao, Yixuan Wang, Zhang Xuewu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Pharmacology, Vol 15 (2024)
Druh dokumentu: article
ISSN: 1663-9812
DOI: 10.3389/fphar.2024.1459520
Popis: 4′,5,7-Trihydroxy-8-methoxyflavone is an anticancer monomer component isolated from the traditional Chinese medicine Sorbaria sorbifolia. 4′,5-Dihydroxy-7-piperazinemethoxy-8-methoxy flavonoids (DMF) with good solubility and anti-tumor effects was obtained by chemical modification in the early stage. This study explored the mechanism by which DMF regulates the mitochondrial apoptosis of human hepatoma cells through Bcl-2-associated transcription factor 1 (Bclaf1). DMF inhibited the proliferation of human hepatoma cells in a concentration- and time-dependent manner and induced cell mitochondrial apoptosis. The molecular docking and cell assay results demonstrated that DMF inhibits Bclaf1 expression by binding to its active site. Lentivirus transfection was used to construct cells with stable knockout and overexpression of Bclaf1, and a Hep3B xenograft model was constructed in nude mice. The mechanism by which DMF induced the mitochondrial apoptosis of human hepatoma cells through Bclaf1 was further verified in vitro and in vivo. These findings indicated that DMF induced human hepatoma cell mitochondrial apoptosis through Bclaf1.
Databáze: Directory of Open Access Journals