萨潘卡尔康通过氧化应激驱动的DNA损伤和通过PIEZO1调制的ER应激激活抑制NSCLC
Weiyu Wu1,2, Ren Zhang2, Geer Chen2
1Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
iScience
|December 16, 2025
概括
一种天然化合物Sappanchalcone (SC) 通过破坏和ER应激通路,有效地抑制非小细胞肺癌 (NSCLC) 细胞生长,从而导致细胞循环停止. 这一发现为NSCLC治疗提供了一个有前途的新途径.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 自然化合物是开发新型抗癌疗法的关键支架.
- 从自然来源中识别有力的抗癌剂是药物发现的关键策略.
研究的目的:
- 为了识别和表征具有抗癌活性的天然化合物对非小细胞肺癌 (NSCLC) 细胞.
- 为了阐明基底的分子机制的抗瘤作用的已识别的化合物.
主要方法:
- 1880年天然化合物的高通量选.
- 细胞测试以评估增殖,细胞循环停止和细胞内水平.
- 转录组和蛋白质-蛋白质相互作用网络分析.
- 西方涂抹分析蛋白质表达和通路激活.
主要成果:
- 萨潘卡尔 (SC) 被确定为H1975,H1299和A549NSCLC细胞的强有力的抑制剂.
- SC诱导了细胞内升高,G2/M阶段停止和ROS积累.
- SC调节的氧化应激,细胞循环调节器 (P21,GADD45α),ER应激通路 (IRE1α,PERK) 和下调的PIEZO1.
- 通过红 (RR) 抑制PIEZO1,逆转了SC诱导的影响.
结论:
- 通过多目标机制,SC通过多目标机制对NSCLC细胞表现出显著的抗瘤活性.
- 该机制涉及-ER应激细胞循环轴,突出显示了SC作为NSCLC治疗剂的潜力.
相关概念视频
Abnormal Proliferation
5.1K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.1K
The Intrinsic Apoptotic Pathway
8.2K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.2K
Interactions Between Signaling Pathways
7.1K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.1K
DNA Damage Can Stall the Cell Cycle
3.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.0K
DNA Damage can Stall the Cell Cycle
9.9K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.9K
Negative Regulator Molecules
38.2K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.2K

