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姜黄素对 NF-κB 表达的调控;在调控肝癌细胞中促炎细胞因子和程序性细胞死亡中的作用。

Regulation of NF-κB Expression by Thymoquinone; A Role in Regulating Pro-Inflammatory Cytokines and Programmed Cell Death in Hepatic Cancer Cells.

机构信息

Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Egypt.

出版信息

Asian Pac J Cancer Prev. 2023 Nov 1;24(11):3739-3748. doi: 10.31557/APJCP.2023.24.11.3739.

DOI:10.31557/APJCP.2023.24.11.3739
PMID:38019231
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10772774/
Abstract

BACKGROUND

The miracle herb Nigella sativa (N. sativa) is a member of the Ranunculaceae family that possesses many properties, such as antioxidant, anticancer, analgesic, antibacterial, and anti-inflammatory. Thymoquinone (TQ) is the primary ingredient that makes up N. sativa, which is responsible for its many properties. So, our research focused on the biological role of TQ and its anticancer activities.

METHODS

A wide range of TQ concentrations (50µg/µl, 25µg/ µl, and 12.5µg µl) was prepared and evaluated for their potential regulatory role in cell lines of hepatocellular carcinoma (HepG2 cell line) compared with normal hepatocytes cells, untreated and DMSO-treated cells.

RESULTS

The more significant level of LDH obtained after TQ treatment compared to untreated cells provides evidence of the cytotoxic effects of TQ on HepG2 cells. Notably, the normal hepatocyte cells subjected to the same concentrations of TQ showed neglected influence in cell viability rate, indicating the selective regulatory role of TQ in cancer cell proliferation. Interestingly, as a critical mediator of malignancy transformation, the nuclear factor-kappa B expression level (NF-κB) significantly decreased in a time and dose-dependent manner of TQ treatment. Furthermore, we investigated whether TQ regulates the expression of deleted liver cancer 1 (DLC1) and Caspase 3 (Casp3). Notably, the treatment with TQ showed increased expression levels of DLC1 and Casp3 upon treatment. TQ extract sufficiently mediated the secretion of the released pro-inflammatory cytokines from treated cells. This regulation of released cytokines by TQ may affect the activation of NF-κB in treated cells.

CONCLUSION

These results indicate that TQ mediates the activation of Casp3, DLC1, and NF-κB, providing a new function of TQ in treating hepatocellular carcinoma (HCC).

摘要

背景

神奇草药黑种草(N. sativa)属于毛茛科,具有抗氧化、抗癌、镇痛、抗菌和抗炎等多种特性。其主要成分是百里醌(TQ),这也是其多种特性的来源。因此,我们的研究集中在 TQ 的生物作用及其抗癌活性上。

方法

我们制备了一系列不同浓度(50μg/μl、25μg/μl 和 12.5μg/μl)的 TQ,以评估其在肝癌细胞系(HepG2 细胞系)与正常肝细胞、未经处理和 DMSO 处理的细胞中的潜在调节作用。

结果

与未经处理的细胞相比,TQ 处理后获得的更高水平的 LDH 表明 TQ 对 HepG2 细胞具有细胞毒性作用。值得注意的是,相同浓度的 TQ 作用于正常肝细胞时对细胞活力几乎没有影响,表明 TQ 对癌细胞增殖具有选择性调节作用。有趣的是,核因子-κB(NF-κB)作为恶性转化的关键介质,其表达水平随 TQ 处理时间和剂量的增加呈下降趋势。此外,我们研究了 TQ 是否调节删除的肝癌 1(DLC1)和 Caspase 3(Casp3)的表达。值得注意的是,TQ 处理后 DLC1 和 Casp3 的表达水平均增加。TQ 提取物足以介导处理细胞中释放的促炎细胞因子的分泌。TQ 对释放细胞因子的调节可能会影响处理细胞中 NF-κB 的激活。

结论

这些结果表明,TQ 介导 Casp3、DLC1 和 NF-κB 的激活,为 TQ 治疗肝细胞癌(HCC)提供了新的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3058/10772774/e2f232ff197f/APJCP-24-3739-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3058/10772774/a791180c68e9/APJCP-24-3739-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3058/10772774/b6c6affb0421/APJCP-24-3739-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3058/10772774/1787a6e7b5b6/APJCP-24-3739-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3058/10772774/e2f232ff197f/APJCP-24-3739-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3058/10772774/a791180c68e9/APJCP-24-3739-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3058/10772774/b6c6affb0421/APJCP-24-3739-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3058/10772774/1787a6e7b5b6/APJCP-24-3739-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3058/10772774/e2f232ff197f/APJCP-24-3739-g004.jpg

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