拜卡莱因通过阻断JAK2/STAT3/GPX4轴来触发结直肠癌细胞中的铁亡
Jian-Qin Lai1,2,3, Le-le Zhao2, Chao Hong2,4
1Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510630, China.
Acta pharmacologica Sinica
|April 29, 2024
概括
拜卡莱因通过抑制JAK2/STAT3/GPX4信号轴,通过新型细胞死亡途径ferroptosis诱导癌细胞死亡. 这种天然化合物对结直肠癌的治疗有望,毒性降低.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 结肠直肠癌 (CRC) 在化疗耐药性和副作用方面提出了重大挑战.
- 铁亡是一种受调节的细胞死亡途径,为癌症治疗提供了一个有前途的治疗策略.
- 贝卡莱因是来自Scutellaria baicalensis的天然黄,具有已知的抗癌特性.
研究的目的:
- 研究贝卡莱因抗CRC活性的机制,特别是其在诱导铁亡中的作用.
- 阐明参与CRC细胞中贝卡林介导铁亡的信号通路.
- 评估贝卡莱因在临床前CRC模型中的治疗潜力.
主要方法:
- 在用baicalein治疗的人类CRC细胞系 (HCT116,DLD1) 上进行细胞活力测定.
- 与特定的细胞死亡抑制剂 (ferroptosis,自,死细胞,亡) 进行并发治疗的实验.
- RNA测序 (RNA-seq) 用于分析基因表达变化.
- 西方斑点测试用于评估JAK2,STAT3和GPX4.4的蛋白质水平.
- 使用CRC异种移植小鼠模型进行体内研究.
主要成果:
- 拜卡莱因剂量依赖地抑制了CRC细胞活力.
- 利普罗克斯塔丁-1 (ferroptosis抑制剂) 缓解了拜卡林诱导的细胞死亡,而其他抑制剂没有.
- 拜卡莱因通过阻断JAK2/STAT3信号通路来降低GPX4表达.
- 在CRC异种移植模型中,Baicalein的使用抑制了瘤生长,通过JAK2/STAT3/GPX4轴诱导铁亡.
结论:
- 拜卡莱因诱导结直肠癌细胞中的铁亡.
- 贝卡莱因的抗CRC作用是通过抑制JAK2/STAT3/GPX4信号通路进行介导的.
- 拜卡莱因通过诱导铁死来证明了结直肠癌治疗的治疗潜力.
相关概念视频
Drugs that Stabilize Microtubules
2.0K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.0K
The Intrinsic Apoptotic Pathway
6.5K
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...
6.5K
The JAK-STAT Signaling Pathway
8.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.8K
Drugs that Destabilize Microtubules
2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
Targeted Cancer Therapies
7.6K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.6K
NF-κB-dependent Signaling Pathway
7.4K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.4K


