黄类药物调节质母细胞瘤和微质母细胞瘤中的氧反应性转录因子
Natali Joma1, Issan Zhang1, Germanna L Righetto1,2
1Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, QC H3G 1Y6, Canada.
Cells
|December 22, 2023
概括
天然化合物菲塞丁和奎尔丁对抗质母细胞瘤有前途. 菲塞有效调节微质中的关键细胞通路,这表明质母细胞瘤治疗的向治疗方法.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 质母细胞瘤 (GBM) 中的瘤微环境 (TME) 通过活性氧物种 (ROS) 和免疫细胞透促进癌症生长.
- 微质积聚在GBM中,支持瘤增殖和血管生成.
- 天然多具有抗氧化和抗炎性质,提供潜在的治疗途径.
研究的目的:
- 调查fisetin和quercetin在质母细胞瘤中的治疗潜力.
- 探索它们作为氧化回应转录因子调节者的作用.
- 确定这些化合物与标蛋白的相互作用部位和结合亲和性.
主要方法:
- 利用2D培养物和3D瘤体来评估细胞效应.
- 采用分子对接和近距离结合试验来研究化合物-蛋白质相互作用.
- 特定蛋白质表达的量化变化,如乙化高流动性组框1 (acHMGB1) 和转录因子EB (TFEB).
主要成果:
- 菲西在微质细胞中降低了细胞质acHMGB1并增加了TFEB,但不是在GBM细胞中.
- 与奎尔塞丁相比,费塞丁显示了Nrf2-KEAP1复合物的优异调节.
- 分子建模表明,费塞与Nrf2-KEAP1.1之间具有更强的结合亲和力和更多的相互作用部位.
结论:
- 菲塞丁和奎尔丁对质母细胞瘤和相关的微质细胞有不同的作用.
- 菲塞显示出作为氧化回归敏感通路的调节剂的显著潜力,特别是通过Nrf2-KEAP1复合体.
- 这些发现支持将菲塞作为质母细胞瘤的向治疗方法的发展.
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