西斯丁与血管原蛋白结合:新分子途径和向药物的抗癌活性
Giarita Ferraro1, Vanessa Sanfilippo2, Lorenzo Chiaverini3
1Department of Chemical Sciences, University of Naples Federico II, via Cintia 21, I-80126 Napoli, Italy. antonello.merlino@unina.it.
Dalton transactions (Cambridge, England : 2003)
|June 20, 2023
概括
这项研究探讨了思丁如何与血管新生素 (一种与癌症相关的蛋白质) 相互作用. 由此产生的复杂物会影响癌细胞的活力,并为青引入新的可能性.
科学领域:
- 生物化学和分子生物学
- 癌症研究 癌症研究
- 结构生物学 结构生物学
背景情况:
- 西斯 (CisPt) 是一种基于的化疗药物,通过DNA损伤和细胞骨变化向癌细胞.
- 蛋白质相互作用可以影响CisPt的疗效,并导致药物耐药性.
- 血管新生素 (Ang) 是一种在许多癌症中过度表达的蛋白质,促进血管新生.
研究的目的:
- 为了研究思普拉丁与血管原蛋白之间的相互作用.
- 要描述由此产生的西斯-血管原蛋白添加物 (Ang@CisPt).
- 评估Ang@CisPt adduct对前列腺癌细胞的生物学影响.
主要方法:
- 用X射线结晶学来确定血管新生素的化部位.
- 紫外线可见的吸收和循环二极化谱镜,以评估形状变化.
- 电子喷雾电离质谱仪用于静态测量分析.
- 色度测试和激光扫描共聚焦显微镜,以评估细胞对PC-3前列腺癌细胞的影响.
主要成果:
- 确定了西斯普拉丁在血管原蛋白上确切的结合部位.
- Ang@CisPt adduct形成诱导了蛋白质构成的变化.
- 附带影响了前列腺癌细胞活力,线粒体损伤,ROS生产和细胞骨组织.
结论:
- 西斯普拉丁可以与血管新生素形成一种特征的附加物.
- 这种Ang@CisPt adduct对前列腺癌细胞表现出细胞毒性作用.
- 这些发现表明新的分子途径和潜在的治疗基基癌症治疗的潜在治疗点.
相关概念视频
02:57Targeted Cancer Therapies
7.7K
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...
7.7K
01:24Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
02:34Inhibition of Cdk Activity
4.8K
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...
4.8K
01:10Drugs 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
01:10Mechanism of Angiogenesis
5.6K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.6K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
7.5K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.5K