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双氢青蒿素通过调节 ROS 产生诱导人舌鳞癌细胞内质网应激介导的凋亡。

Dihydroartemisinin Induces ER Stress-Mediated Apoptosis in Human Tongue Squamous Carcinoma by Regulating ROS Production.

机构信息

Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.

出版信息

Anticancer Agents Med Chem. 2022 Aug 4;22(16):2902-2908. doi: 10.2174/1871520622666220215121341.

DOI:10.2174/1871520622666220215121341
PMID:35168525
Abstract

BACKGROUND

Tongue squamous cell carcinoma is a fatal disease characterized by high invasion and early metastasis. Dihydroartemisinin, an antimalarial drug with multiple biological activities, is reported to be a potential anti-cancer agent.

OBJECTIVE

This study aimed to evaluate the antitumor effect of Dihydroartemisinin on tongue squamous cell carcinoma cells, and to identify the underlying mechanisms of Dihydroartemisinin-induced cell apoptosis.

METHODS

Here, Cell Counting Kit 8 assay and colony formation assay were conducted to study cell proliferation. Annexin V-FITC/propidium iodide staining and western blot analysis were performed to analyze cell apoptosis. DCFHDA probe was used to measure the generation of cellular reactive oxygen species. Endoplasmic reticulum stress activation was also determined via western blot analysis.

RESULTS

The results showed that Dihydroartemisinin substantially inhibited cell proliferation and induced cell apoptosis in vivo. Moreover, reactive oxygen species production and endoplasmic reticulum stress activation were both observed after stimulation with Dihydroartemisinin. However, the reactive oxygen species inhibitor N-acetylcysteine significantly alleviated Dihydroartemisinin-induced endoplasmic reticulum stress and apoptosis.

CONCLUSION

These results imply that Dihydroartemisinin induced cell apoptosis by triggering reactive oxygen speciesmediated endoplasmic reticulum stress in CAL27 cells. In addition, Dihydroartemisinin might be an effective drug for tongue squamous cell carcinoma therapy.

摘要

背景

舌鳞状细胞癌是一种致命疾病,其特征为高侵袭性和早期转移。二氢青蒿素是一种具有多种生物学活性的抗疟药物,据报道其是一种有潜力的抗癌药物。

目的

本研究旨在评估二氢青蒿素对舌鳞状细胞癌细胞的抗肿瘤作用,并确定二氢青蒿素诱导细胞凋亡的潜在机制。

方法

在这里,使用细胞计数试剂盒 8 检测和集落形成实验来研究细胞增殖。使用 Annexin V-FITC/碘化丙啶染色和 Western blot 分析来分析细胞凋亡。使用 DCFHDA 探针来测量细胞内活性氧的产生。还通过 Western blot 分析来确定内质网应激的激活情况。

结果

结果表明,二氢青蒿素可显著抑制体内细胞增殖并诱导细胞凋亡。此外,在受到二氢青蒿素刺激后,还观察到活性氧的产生和内质网应激的激活。然而,活性氧抑制剂 N-乙酰半胱氨酸可显著缓解二氢青蒿素诱导的内质网应激和凋亡。

结论

这些结果表明,二氢青蒿素通过触发活性氧介导的内质网应激诱导 CAL27 细胞凋亡。此外,二氢青蒿素可能是治疗舌鳞状细胞癌的有效药物。

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引用本文的文献

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ER Stress Induced by Artemisinin and Its Derivatives Determines the Susceptibility to Their Synergistic Apoptotic Killing With TRAIL.青蒿素及其衍生物诱导的内质网应激决定了它们与TRAIL协同凋亡杀伤的敏感性。
Cancer Med. 2025 Jun;14(12):e71001. doi: 10.1002/cam4.71001.
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[Dihydroartemisinin enhances sensitivity of nasopharyngeal carcinoma HNE1/DDP cells to cisplatin-induced apoptosis by promoting ROS production].双氢青蒿素通过促进活性氧生成增强鼻咽癌HNE1/DDP细胞对顺铂诱导凋亡的敏感性
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Aug 20;44(8):1553-1560. doi: 10.12122/j.issn.1673-4254.2024.08.14.
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Repurposing Dihydroartemisinin to Combat Oral Squamous Cell Carcinoma, Associated with Mitochondrial Dysfunction and Oxidative Stress.
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Oxid Med Cell Longev. 2023 Feb 16;2023:9595201. doi: 10.1155/2023/9595201. eCollection 2023.