Chen Jiaxin, Cheng Haoyi, Bai Chunhua, Wang Dandan, Fu Jinghao, Hao Jinge, Wang Yixuan, Xuewu Zhang
College of Medicine, Yanbian University, Yanji, China.
Front Pharmacol. 2024 Oct 9;15:1459520. doi: 10.3389/fphar.2024.1459520. eCollection 2024.
4',5,7-Trihydroxy-8-methoxyflavone is an anticancer monomer component isolated from the traditional Chinese medicine . 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 and . These findings indicated that DMF induced human hepatoma cell mitochondrial apoptosis through Bclaf1.
4',5,7-三羟基-8-甲氧基黄酮是从中药中分离得到的一种抗癌单体成分。前期通过化学修饰得到了溶解性良好且具有抗肿瘤作用的4',5-二羟基-7-哌嗪甲氧基-8-甲氧基黄酮(DMF)。本研究探讨了DMF通过Bcl-2相关转录因子1(Bclaf1)调控人肝癌细胞线粒体凋亡的机制。DMF以浓度和时间依赖性方式抑制人肝癌细胞增殖并诱导细胞线粒体凋亡。分子对接和细胞实验结果表明,DMF通过与Bclaf1的活性位点结合抑制其表达。利用慢病毒转染构建了稳定敲除和过表达Bclaf1的细胞,并在裸鼠中构建了Hep3B异种移植模型。进一步验证了DMF通过Bclaf1诱导人肝癌细胞线粒体凋亡的机制。这些研究结果表明,DMF通过Bclaf1诱导人肝癌细胞线粒体凋亡。