Related Experiment Video
Updated: Jul 19, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Conoidin A, a Covalent Inhibitor of Peroxiredoxin 2, Reduces Growth of Glioblastoma Cells by Triggering ROS
Monika Szeliga1, Radosław Rola2
1Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland.
Abstract:
Compounds that cause oxidative stress have recently gained considerable interest as potential anticancer treatment modalities. Nevertheless, their efficiency may be diminished by the antioxidant systems often upregulated in cancer cells. Peroxiredoxins (PRDXs) are antioxidant enzymes that scavenge peroxides and contribute to redox homeostasis. They play a role in carcinogenesis and are upregulated in several cancer types. Here, we assessed the expression pattern of PRDX1 and PRDX2 in glioblastoma (GBM) and examined the efficacy of their inhibitors in GBM cell lines and patient-derived GBM cells. Both PRDX1 and PRDX2 were upregulated in GBM compared to non-tumor brain tissues and their considerable amounts were observed in GBM cells. Adenanthin, a compound inhibiting PRDX1 activity, slightly decreased GBM cell viability, while conoidin A (CONA), a covalent PRDX2 inhibitor, displayed high toxicity in GBM cells. CONA elevated the intracellular reactive oxygen species (ROS) level. Pre-treatment with an ROS scavenger protected cells from CONA-induced death, indicating that ROS accumulation plays a crucial role in this phenomenon. Menadione or celecoxib, both of which are ROS-inducing agents, potentiated the anticancer activity of CONA. Collectively, our results unveil PRDX1 and PRDX2 as potential targets for GBM therapy, and substantiate the further exploration of their inhibitors.
Insights
Peroxiredoxins (PRDXs) are upregulated in glioblastoma (GBM). PRDX2 inhibitors like conoidin A show high toxicity in GBM cells by increasing reactive oxygen species (ROS), suggesting PRDXs as potential GBM therapeutic targets.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Oxidative stress-inducing compounds are investigated for cancer therapy.
- Antioxidant systems, including Peroxiredoxins (PRDXs), are often upregulated in cancer cells, potentially limiting treatment efficacy.
- PRDXs are antioxidant enzymes involved in redox homeostasis and implicated in carcinogenesis.
Purpose of the Study:
- To investigate the expression of PRDX1 and PRDX2 in glioblastoma (GBM).
- To evaluate the efficacy of PRDX1 and PRDX2 inhibitors in GBM cell lines and patient-derived cells.
Main Methods:
- Assessed PRDX1 and PRDX2 expression in GBM tissues and cells.
- Tested the effects of PRDX inhibitors (adenanthin for PRDX1, conoidin A for PRDX2) on GBM cell viability.
- Investigated the role of reactive oxygen species (ROS) in conoidin A's mechanism of action.
- Examined the potentiation of conoidin A's activity by ROS-inducing agents.
Main Results:
- PRDX1 and PRDX2 were found to be upregulated in GBM compared to non-tumor tissues.
- Conoidin A (CONA), a PRDX2 inhibitor, exhibited significant toxicity against GBM cells.
- CONA treatment led to increased intracellular ROS levels, and ROS scavengers protected cells from CONA-induced death.
- ROS-inducing agents (menadione, celecoxib) enhanced CONA's anticancer effects.
Conclusions:
- PRDX1 and PRDX2 are upregulated in GBM and represent potential therapeutic targets.
- PRDX2 inhibition, particularly with agents like CONA that induce ROS, shows promise for GBM treatment.
- Further research into PRDX inhibitors is warranted for GBM therapy development.
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
01:24Peroxisomes