ArticleThe Journal of biological chemistry2010
The in vivo toxicity of hydroxyurea depends on its direct target catalase.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Trial
- A redox-regulated RCC1-like protein controls catalase activity in Arabidopsis.Nature communications · 2026Article
- Hydroxyurea modulates thiol-disulfide homeostasis in the yeast endoplasmic reticulum.Life science alliance · 2025Article
- Revised mechanism of hydroxyurea-induced cell cycle arrest and an improved alternative.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Oxidative replication stress induced by long-term exposure to hydroxyurea in root meristem cells of Vicia faba.Plant cell reports · 2024Article
- Allelic variation of TaWD40-4B.1 contributes to drought tolerance by modulating catalase activity in wheat.Nature communications · 2023Article
- Genome-wide CRISPR screens reveal cyclin C as synthetic survival target of BRCA2.Nucleic acids research · 2021Article
- Relationship between Oxidative Stress and Imatinib Resistance in Model Chronic Myeloid Leukemia Cells.Biomolecules · 2021Article
- Auxin-Glucose Conjugation Protects the Rice (Frontiers in plant science · 2021Article
- The AP2 transcription factor NtERF172 confers drought resistance by modifying NtCAT.Plant biotechnology journal · 2020Article
- Sickle Cell Anemia: Variants in theFrontiers in pharmacology · 2020Article
- Attenuation potentials of royal jelly against hydroxyurea-induced infertility through inhibiting oxidation and release of pro-inflammatory cytokines in male rats.Environmental science and pollution research international · 2019Article
- A facile forward-genetic screen for Arabidopsis autophagy mutants reveals twenty-one loss-of-function mutations disrupting six ATG genes.Autophagy · 2019Article
- Two NCA1 isoforms interact with catalase in a mutually exclusive manner to redundantly regulate its activity in rice.BMC plant biology · 2019Article
- Hydroxyurea in the management of sickle cell disease: pharmacogenomics and enzymatic metabolism.The pharmacogenomics journal · 2018Review
- Replication Rapidly Recovers and Continues in the Presence of Hydroxyurea in Escherichia coli.Journal of bacteriology · 2018Article
- Dihydrofolate Reductase/Thymidylate Synthase Fine-Tunes the Folate Status and Controls Redox Homeostasis in Plants.The Plant cell · 2017Article
- Heme deficiency sensitizes yeast cells to oxidative stress induced by hydroxyurea.The Journal of biological chemistry · 2017Article
- The Cell Killing Mechanisms of Hydroxyurea.Genes · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hydroxyurea (HU) is a well tolerated ribonucleotide reductase inhibitor effective in HIV, sickle cell disease, and blood cancer therapy. Despite a positive initial response, however, most treated cancers eventually progress due to development of HU resistance. Although RNR properties influence HU resistance in cell lines, the mechanisms underlying cancer HU resistance in vivo remain unclear. To address this issue, we screened for HU resistance in the plant Arabidopsis thaliana and identified seventeen unique catalase mutants, thereby establishing that HU toxicity depends on catalase in vivo. We further demonstrated that catalase is a direct HU target by showing that HU acts as a competitive inhibitor of catalase-mediated hydrogen peroxide decomposition. Considering also that catalase can accelerate HU decomposition in vitro and that co-treatment with another catalase inhibitor alleviates HU effects in vivo, our findings suggests that HU could act as a catalase-activated pro-drug. Clinically, we found high catalase activity in circulating cells from untreated chronic myeloid leukemia, offering a possible explanation for the efficacy of HU against this malignancy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.