2,2'-联吡啶衍生物通过诱导肝细胞癌(HepG2)细胞凋亡发挥抗癌作用

IF 4.2 3区 医学 Q2 ONCOLOGY
Journal of Hepatocellular Carcinoma Pub Date : 2024-11-09 eCollection Date: 2024-01-01 DOI:10.2147/JHC.S479463
Priyanka, Somdutt Mujwar, Ram Bharti, Thakur Gurjeet Singh, Neeraj Khatri
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引用次数: 0

摘要

目的:阐明 2,2'-联吡啶衍生物[NPS(1-6)]对肝癌 HepG2 细胞的治疗潜力:方法:研究了 2,2'-联吡啶衍生物[NPS(1-6)]对肝癌 HepG2 细胞存活、集落形成、细胞和核形态、活性氧(ROS)生成、线粒体膜电位(MMP)完整性变化和细胞凋亡的影响。此外,还进行了对接研究,以分析和阐明这些衍生物与 AKT 和 BRAF 蛋白之间的相互作用:结果:NPS 衍生物(1、2、5 和 6)在纳克级浓度(72.11 毫微克/毫升、154.42 毫微克/毫升、71.78 毫微克/毫升和 71.43 毫微克/毫升)下显著降低了 HepG2 细胞系的细胞活力,而其他衍生物在浓度低于 1 微克/毫升时也有效。这些化合物在处理后以剂量依赖的方式降低了 HepG2 细胞的集落形成能力。机理研究显示,这些衍生物会诱导活性氧(ROS)积累,导致线粒体膜去极化,最终引发 HepG2 细胞凋亡。在有这些衍生物存在的情况下,细胞凋亡率为 75%,而对照组为 25%。此外,与对照组相比,线粒体去极化明显增加(95% 的细胞),ROS 水平上升了三倍。对接研究显示,这些衍生物与信号蛋白 AKT(PDB ID:6HHF)和 BRAF(PDB ID:8C7Y)之间存在相互作用,结合亲和力从 -7.10 到 -9.91,突出了它们在靶向肝细胞癌进展过程中的关键作用:本研究的发现强调了这些衍生物对 HepG2 细胞的治疗潜力,并为进一步实验验证它们作为靶向 AKT 或 BRAF 信号通路的抑制剂的功效提供了宝贵的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
2,2'- Bipyridine Derivatives Exert Anticancer Effects by Inducing Apoptosis in Hepatocellular Carcinoma (HepG2) Cells.

Purpose: To elucidate the therapeutic potential of 2,2'-bipyridine derivatives [NPS (1-6)] on hepatocellular carcinoma HepG2 cells.

Methods: The effects on cell survival, colony formation, cellular and nuclear morphology, generation of reactive oxygen species (ROS), change in the integrity of mitochondrial membrane potential (MMP), and apoptosis were investigated. Additionally, docking studies were conducted to analyze and elucidate the interactions between the derivatives and AKT and BRAF proteins.

Results: NPS derivatives (1, 2, 5 and 6) significantly impaired cell viability of HepG2 cell lines at nanogram range concentrations - 72.11 ng/mL, 154.42 ng/mL, 71.78 ng/mL, and 71.43 ng/mL, while other derivatives were also effective at concentrations below 1 µg/mL. These compounds reduced the colony formation capacity of HepG2 cells in a dose-dependent manner following treatment. Mechanistic studies revealed that these derivatives induce reactive oxygen species (ROS) accumulation and cause mitochondrial membrane depolarization, ultimately triggering apoptosis in HepG2 cells. In the presence of these derivatives, cells demonstrated that 75% of cells underwent apoptosis, compared to 25% in the control group. Additionally, there was a marked increase in mitochondrial depolarization (95% cells) and a threefold rise in ROS levels compared to the controls. Docking studies revealed interactions between the derivatives and the signaling proteins AKT (PDB ID: 6HHF) and BRAF (PDB ID: 8C7Y) with binding affinities ranging from -7.10 to -9.91, highlighting their pivotal role in targeting key players in hepatocellular carcinoma progression.

Conclusion: The findings of this study underscore the therapeutic potential of these derivatives against HepG2 cells and offer valuable insights for further experimental validation of their efficacy as inhibitors targeting AKT or BRAF signaling pathways.

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来源期刊
CiteScore
0.50
自引率
2.40%
发文量
108
审稿时长
16 weeks
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