合成诱导人类结肠直肠癌细胞死亡通过proapoptotic途径
Felipe P Mesquita1, Francisco L de Oliveira1, Emerson L da Silva1
1Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, CE 60430-275, Brazil.
ACS omega
|October 28, 2024
概括
抗微生物PepGAT和PepKAA在治疗结直肠癌 (CRC) 中表现有前途. 这些可以诱导癌细胞死亡并抑制侵袭,而不会伤害正常细胞,这为抗药性癌症提供了潜在的新策略.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 癌症中药物和化疗耐药性对全球健康构成重大挑战.
- 重用抗微生物 (AMP) 提供了一种有希望的策略来克服癌症耐药性.
- 现有研究表明AMP对癌细胞具有细胞毒性作用.
研究的目的:
- 研究将抗微生物PepGAT和PepKAA重新用于癌症治疗的潜力.
- 评估PepGAT和PepKAA对结直肠癌 (CRC) 细胞的疗效和作用机制.
- 评估这些在正常人体细胞中的安全性.
主要方法:
- 对PepGAT和PepKAA对各种癌症细胞系的查.
- 对结直肠癌 (CRC) 细胞的IC50值的确定.
- 细胞循环进展,亡诱导 (caspase 3/7试验,流细胞计,qPCR),反应性氧物种 (ROS) 生产和膜透的分析.
- 细胞入侵抑制的评估.
- 在正常人细胞中评估细胞毒性.
主要成果:
- 佩普加特和佩普卡对CRC细胞具有显著的细胞毒性,其IC50值分别为125.42微米和40.51微米.
- 这两种都在HCT-116细胞中诱导了G2/M细胞周期停止和细胞亡,通过基因表达调节和生物化学分析证实了这一点.
- 类化合物导致ROS过度积累,增加了膜透性,并抑制了细胞入侵.
- 以前的研究证实对正常人细胞没有毒性.
结论:
- 抗微生物PepGAT和PepKAA对结直肠癌具有强大的抗癌活性.
- 该机制涉及诱导亡,细胞循环停止,ROS生成和膜损伤.
- 这些具有作为癌症治疗的新型治疗剂的潜力,特别是在克服耐药性方面,具有有利的安全性.
相关概念视频
The Extrinsic Apoptotic Pathway
6.3K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.3K
The Intrinsic Apoptotic Pathway
6.4K
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...
6.4K
Apoptosis
11.2K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
11.2K
Overview of Cell Death
7.1K
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...
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...
7.1K
Caspases
12.3K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.3K
Phagocytosis of Apoptotic Cells
3.7K
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized...
Normal cells contain receptors that prevent them from being recognized...
3.7K


