相关实验视频

Updated: Jul 1, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

合成和线粒体局部化的 (III) 复合体通过热和铁的途径诱导细胞死亡

Huiyan Hu¹, Fan Zhang¹, Zhujun Sheng¹

¹School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.

European journal of medicinal chemistry

|March 4, 2024

概括

新的与DPPA连接体结合的 (III) 复合物对各种癌细胞系表现出强大的抗癌活性. 这些复杂物通过铁灭,灭和热灭诱导细胞死亡,其中一个复杂物在体内显著抑制瘤生长.

科学领域:

协调化学协调化学
药用化学医学化学
癌症生物学癌症生物学

背景情况:

开发新的基于金属的抗癌剂对于克服药物耐药性至关重要.
(III) 复合物因其独特的光物理和细胞毒性特性而成为有前途的候选物.

研究的目的:

为了合成和表征一种新的 (III) 复合物与一种新型DPPA配体.
评估合成复合物的体外和体内抗癌效果.
阐明由这些复杂物诱导的细胞死亡的潜在机制.

主要方法:

(III) 复合物的合成和表征: [Ir(ppy) 2 DPPA] PF6 (2a), [Ir(bzq) 2 DPPA] PF6 (2b) 和 [Ir(piq) 2 DPPA] PF6 (2c).
在体外细胞毒性测定 (MTT) 对A549,B16,HCT116,HepG2和LO2细胞系.
细胞循环分析,细胞亡试验,ROS和Ca2+水平测量,线粒体功能研究,铁亡和热亡调查,RNA测序和西斑分析.
在携带瘤的小鼠模型中对复合2c进行体内抗瘤研究.

主要成果:

复合体2a,2b和2c对A549,B16和HCT116癌细胞表现出显著的细胞毒性.
这些复合物诱导S相停止,亡 (早期/晚期),铁亡和热亡,由ROS诱导的线粒体功能障碍和GSDMD激活介导.
复杂2c在体内显示了58.58%的瘤生长抑制率.

结论:

新型的 (III) 复合物通过多种细胞死亡途径表现出强大的抗癌活性.
这些发现突显了这些复合物的潜力,这些复合物作为癌症治疗的新疗法.
这项研究提供了对 (III) 复合物的抗癌作用的机制性见解,涉及线粒体功能障碍和调节的细胞死亡.

关键词:

在活体中抗瘤.铁化是铁化的一种.(III) 复合物中的 (III) 复合物热灭菌的发生.的RNA-序列.

更多相关视频

Synthesis and Evaluation of a Ruthenium-based Mitochondrial Calcium Uptake Inhibitor

Synthesis and Evaluation of a Ruthenium-based Mitochondrial Calcium Uptake Inhibitor

Published on: October 26, 2017

Synthesis of an In vivo MRI-detectable Apoptosis Probe

Synthesis of an In vivo MRI-detectable Apoptosis Probe

Published on: July 31, 2012

相关概念视频

Electron Transport Chain: Complex I and II

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...

Necrosis

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...

Overview of Cell Death

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...

Electron Transport Chain: Complex III and IV

Electron Transport Chain: Complex III and IV

During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...

The Electron Transport Chain

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...

The Intrinsic Apoptotic Pathway

The Intrinsic Apoptotic Pathway

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...