Auranofin and reactive oxygen species inhibit protein synthesis and regulate the level of the PLK1 protein in Ewing sarcoma cells.
| Autor: | Haight JA; Carver College of Medicine, University of Iowa, Iowa City, IA, United States., Koppenhafer SL; Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, United States., Geary EL; Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, United States., Gordon DJ; Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in oncology [Front Oncol] 2024 Jun 12; Vol. 14, pp. 1394653. Date of Electronic Publication: 2024 Jun 12 (Print Publication: 2024). |
| DOI: | 10.3389/fonc.2024.1394653 |
| Abstrakt: | Novel therapeutic approaches are needed for the treatment of Ewing sarcoma tumors. We previously identified that Ewing sarcoma cell lines are sensitive to drugs that inhibit protein translation. However, translational and therapeutic approaches to inhibit protein synthesis in tumors are limited. In this work, we identified that reactive oxygen species, which are generated by a wide range of chemotherapy and other drugs, inhibit protein synthesis and reduce the level of critical proteins that support tumorigenesis in Ewing sarcoma cells. In particular, we identified that both hydrogen peroxide and auranofin, an inhibitor of thioredoxin reductase and regulator of oxidative stress and reactive oxygen species, activate the repressor of protein translation 4E-BP1 and reduce the levels of the oncogenic proteins RRM2 and PLK1 in Ewing and other sarcoma cell lines. These results provide novel insight into the mechanism of how ROS-inducing drugs target cancer cells via inhibition of protein translation and identify a mechanistic link between ROS and the DNA replication (RRM2) and cell cycle regulatory (PLK1) pathways. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Haight, Koppenhafer, Geary and Gordon.) |
| Databáze: | MEDLINE |
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