桑托胡摩尔通过AMPK-ULK1-FUNDC1信号通路调节骨髓瘤细胞中的食
Qiaofeng Ge1, Zhiliang Yan1, Qian Tian1
1Department of Traumatic Orthopedics, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, Shanxi, China.
Phytotherapy research : PTR
|April 7, 2025
概括
桑托胡醇 (XN) 通过AMPK-ULK1-FUNDC1通路诱导髓细胞的生长和迁移,有效地抑制骨髓瘤 (OS) 细胞的生长和迁移. 这种天然化合物显示出作为OS治疗剂的前景,在体内没有观察到器官毒性.
科学领域:
- 在瘤学瘤学.
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 骨髓瘤 (OS) 是最常见的原发性骨癌,治疗进展有限.
- 黄醇 (XN) 是一种蜂类黄,在其他癌症中表现出抗癌作用,但其在OS中的作用尚不清楚.
研究的目的:
- 为了研究Xanthohumol (XN) 的抗OS作用.
- 阐明XN在OS中的作用背后的分子机制,重点关注菌.
主要方法:
- 在体外测试 (CCK-8,伤口愈合,透洞,克隆原性) 评估了OS细胞的增殖和迁移.
- 使用流细胞计,免疫光学,TEM和西方斑点分析了线粒菌.
- 通过AMP激活蛋白激酶 (AMPK) 敲除,验证了信号通路.
主要成果:
- 在剂量和时间上,XN显著抑制OS细胞的增殖和迁移.
- 通过XN诱导线粒体损伤,增加反应性氧物种 (ROS),并通过上调Atg5,Beclin-1和LC3.3来促进线粒体.
- XN激活了AMPK-ULK1-FUNDC1通路,导致抗OS效应,这些效应被AMPK淘汰扭转.
结论:
- 桑托胡醇 (XN) 通过AMPK-ULK1-FUNDC1通路诱导线粒,表现出强大的抗骨髓瘤活性.
- 在临床前模型中,XN为骨髓瘤提供了一个有前途的治疗策略,其在临床前模型中已证明有效性和安全性.
相关概念视频
mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
PI3K/mTOR/AKT Signaling Pathway
3.3K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.3K
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
The Intrinsic Apoptotic Pathway
5.8K
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...
5.8K
Abnormal Proliferation
4.4K
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...
4.4K
MAPK Signaling Cascades
5.0K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.0K


