BRD4 抑制剂通过向 ROS 和 FSP1 来广泛促进不同细胞系的埃拉斯诱导的铁亡
Chenyang Fan1, Xiaohong Guo1, Jie Zhang1
1Department of Pathogenic Biology, School of Medicine, Nantong University, Nantong, China.
Discover oncology
|April 2, 2024
概括
抑制含有odomain的蛋白4 (BRD4) 增强了铁亡,这是一种细胞死亡途径,对癌症治疗至关重要. 这项研究揭示了BRD4抑制剂增加活性氧物种并降低FSP1的调节,这表明它们在结合癌症治疗中的潜力.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞死亡机制 细胞死亡机制
背景情况:
- 铁,一种依赖于铁的细胞死亡,是一个有前途的癌症治疗策略.
- 含基因的蛋白4 (BRD4) 是一个关键的表观遗传调节器和癌症治疗点.
- 癌症中BRD4抑制和铁亡之间的相互作用仍未得到充分研究.
研究的目的:
- 为了研究BRD4在铁亡中的作用.
- 探索BRD4抑制剂和铁灭诱导剂的联合疗效.
- 阐明BRD4抑制诱导的铁亡背后的分子机制.
主要方法:
- 使用了各种癌症细胞系 (HEK293T,HeLa,HepG2,RKO,PC3).
- 采用BRD4抑制剂 (JQ-1,I-BET-762) 和BRD4抗击剂.
- 评估细胞死亡,活性氧物种 (ROS) 水平和与铁亡相关的基因表达.
- 进行了染色体免疫沉测序 (ChIP-seq) 来分析BRD4结合.
主要成果:
- 在多个细胞系中,BRD4抑制显著增强了埃拉斯诱导的铁亡.
- 抑制BRD4导致ROS积累增加和FSP1下调.
- BRD4直接与FSP1促进体结合,而这种结合通过JQ-1治疗而减少.
结论:
- 抑制BRD4通过ROS积累和FSP1下调来增强铁亡.
- 当与铁死诱导剂相结合时,BRD4抑制剂可能是有效的,特别是在FSP1依赖的癌症中.
- 这项研究突出了针对BRD4与铁亡结合治疗癌症的新疗法策略.
更多相关视频
08:48An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation
Published on: June 30, 2015
8.3K
09:21Ferritinophagy: Assessing the Selective Degradation of Iron by Autophagy in Human Fibroblasts
Published on: February 23, 2024
902
相关概念视频
01:16Necrosis
4.5K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.5K
01:46Electron Transport Chain: Complex I and II
13.2K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
13.2K
01:17Role of ER in the Secretory Pathway
5.4K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
5.4K
01:30The Electron Transport Chain
16.7K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
16.7K
02:34Inhibition of Cdk Activity
4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K