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黄酮类衍生物通过Bclaf1诱导人肝癌细胞发生线粒体凋亡。

flavonoid derivative induces mitochondrial apoptosis in human hepatoma cells through Bclaf1.

作者信息

Chen Jiaxin, Cheng Haoyi, Bai Chunhua, Wang Dandan, Fu Jinghao, Hao Jinge, Wang Yixuan, Xuewu Zhang

机构信息

College of Medicine, Yanbian University, Yanji, China.

出版信息

Front Pharmacol. 2024 Oct 9;15:1459520. doi: 10.3389/fphar.2024.1459520. eCollection 2024.

DOI:10.3389/fphar.2024.1459520
PMID:39444606
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11496133/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/ab6293cab927/fphar-15-1459520-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/8866001de233/fphar-15-1459520-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/eef3024f3a2d/fphar-15-1459520-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/f3817e740331/fphar-15-1459520-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/9f5b99151248/fphar-15-1459520-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/6c6c3e1a2ebe/fphar-15-1459520-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/f79198cdda79/fphar-15-1459520-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/ab6293cab927/fphar-15-1459520-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/8866001de233/fphar-15-1459520-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/eef3024f3a2d/fphar-15-1459520-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/f3817e740331/fphar-15-1459520-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/9f5b99151248/fphar-15-1459520-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/6c6c3e1a2ebe/fphar-15-1459520-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/f79198cdda79/fphar-15-1459520-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/11496133/ab6293cab927/fphar-15-1459520-g007.jpg

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本文引用的文献

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Sci China Life Sci. 2024 Sep;67(9):1881-1898. doi: 10.1007/s11427-023-2514-y. Epub 2024 May 24.
2
BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma.BCLAF1 结合 SPOP 以稳定 PD-L1 并促进肝癌的发展和免疫逃逸。
Cell Mol Life Sci. 2024 Feb 10;81(1):82. doi: 10.1007/s00018-024-05144-z.
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Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers.
免疫耐受机制对原发性和继发性肝癌免疫治疗疗效的影响。
Transl Gastroenterol Hepatol. 2023 Jun 27;8:29. doi: 10.21037/tgh-23-11. eCollection 2023.
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Regulators mount up: the metabolic roles of apoptotic proteins.调节因子增多：凋亡蛋白的代谢作用
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Inhibition of Cell Proliferation and Cell Death by Apigetrin through Death Receptor-Mediated Pathway in Hepatocellular Cancer Cells.芹菜素通过死亡受体介导的途径抑制肝癌细胞的增殖和细胞死亡。
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