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Irisquinone's Anti-cancer Potential: Targeting TrxR to Trigger ROS-mediated Apoptosis and Pyroptosis
Qifeng Zhang1, Xinyan Wang1, Gegen Tana1
1Key Laboratory for Candidate Drug Design and Screening Based on Chemical Biology, College of Pharmacy, Inner Mongolia Medical University, Hohhot, 010110, People's Republic of China.
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 tumor 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.
Insights
Irisquinone demonstrates anticancer activity by inhibiting thioredoxin reductase (TrxR), leading to increased reactive oxygen species (ROS) and inducing apoptosis and pyroptosis in cancer cells. This compound shows potential as a novel anti-tumor drug.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Irisquinone, derived from Semen Irisis, is a known radiotherapy sensitizer for various cancers.
- Its precise anti-cancer mechanism remains largely unelucidated.
Purpose of the Study:
- To investigate the anti-tumor effects of Irisquinone.
- To elucidate the underlying molecular mechanisms of Irisquinone's action.
Main Methods:
- Cell viability and proliferation assessed via CCK-8 assay.
- Thioredoxin reductase (TrxR) inhibition evaluated using Fast-TRFS and DTNB assays.
- Reactive oxygen species (ROS) levels measured with DCFH-DA probe.
- Apoptosis and pyroptosis analyzed by Annexin V-FITC/PI staining and Western blotting.
Main Results:
- Irisquinone exhibited significant anti-proliferative effects on cancer cell lines with minimal toxicity to normal cells.
- Inhibition of TrxR by Irisquinone led to increased intracellular ROS generation.
- Elevated ROS activated BAX and caspase-1, inducing both apoptosis and pyroptosis in cancer cells.
Conclusions:
- Irisquinone exerts anti-cancer activity by inhibiting TrxR, a mechanism that triggers ROS-mediated apoptosis and pyroptosis.
- These findings support the potential development of Irisquinone as a novel anti-tumor therapeutic agent.
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