Irisquinone's Anti-cancer Potential: Targeting TrxR to Trigger ROS-mediated Apoptosis and Pyroptosis.

IF 2.6 4区医学 Q3 CHEMISTRY, MEDICINAL

Anti-cancer agents in medicinal chemistry Pub Date : 2025-01-15 DOI:10.2174/0118715206339230241202062826

Qifeng Zhang, Xinyan Wang, Gegen Tana, Guodong Liang, Yuheng Ma, Ren Bu, Lu Ga

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引用次数: 0

Abstract

Background: Irisquinone, an important compound extracted from Semen Irisis, has been used clinically as a radiotherapy sensitizer for lung, oesophageal, head and neck, breast and leukemia cancers. However, the mechanism by which it acts against cancer is still unclear.

Objective: The present study aims to investigate the anti-tumor activity and mechanism of Irisquinone.

Methods: The effect of Irisquinone on cell viability and proliferation was evaluated using the CCK-8 assay. Fluorescence probe (Fast-TRFS) and DTNB assay were used to observe the inhibitory effect of Irisquinone on both intracellular and extracellular thioredoxin reductase (TrxR). The level of reactive oxygen species (ROS) in tumour cells was assessed using the DCFH-DA probe. Annexin V-FITC/PI, staining and microscopy experiments, were used to examine the apoptosis and pyroptosis. Western blotting analyses confirmed that Irisquinone induced apoptosis and pyroptosis in cancer cells by inhibiting TrxR to increase ROS generation.

Results: Our research has shown that Irisquinone has anti-proliferative effects on several cancer cell lines while having low toxicity to normal cells. The amount of ROS induced by inhibition of TrxR activated the BAX (proapoptotic protein) and caspase-1(the pro-pyroptotic protein) to induce apoptosis and pyroptosis.

Conclusion: Irisquinone showed anticancer activity through inhibiting TrxR. These results suggested that Irisquinone will be developed to be an anti-tumor drug possibility.

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鸢尾醌的抗癌潜力：靶向TrxR触发ros介导的细胞凋亡和焦亡。

背景：鸢尾醌是鸢尾中提取的一种重要化合物，临床上已被用作肺癌、食管癌、头颈癌、乳腺癌和白血病的放疗增敏剂。然而，它对抗癌症的机制仍不清楚。目的：探讨鸢尾醌的抗肿瘤活性及其作用机制。方法：采用CCK-8法观察鸢尾醌对细胞活力和增殖的影响。采用荧光探针（Fast-TRFS）和DTNB法观察鸢尾醌对细胞内和细胞外硫氧还蛋白还原酶（TrxR）的抑制作用。使用DCFH-DA探针评估肿瘤细胞中的活性氧（ROS）水平。采用Annexin V-FITC/PI染色和显微镜观察凋亡和焦亡情况。Western blotting分析证实，鸢尾醌通过抑制TrxR增加ROS生成，诱导癌细胞凋亡和焦亡。结果：我们的研究表明，鸢尾醌对几种癌细胞系具有抗增殖作用，而对正常细胞的毒性较低。抑制TrxR诱导的ROS量激活BAX（促凋亡蛋白）和caspase-1（促焦亡蛋白），诱导细胞凋亡和焦亡。结论：鸢尾醌通过抑制TrxR具有抗癌活性。这些结果提示鸢尾醌将有可能成为一种抗肿瘤药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anti-cancer agents in medicinal chemistry ONCOLOGY-CHEMISTRY, MEDICINAL

CiteScore

5.10

自引率

3.60%

发文量

323

审稿时长

4-8 weeks

期刊介绍： Formerly: Current Medicinal Chemistry - Anti-Cancer Agents. Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents. Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication. Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.