ArticleFree radical biology & medicine2010
Dihydroorotate dehydrogenase is required for N-(4-hydroxyphenyl)retinamide-induced reactive oxygen species production and apoptosis.
Article in Free radical biology & medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 40 citations in OpenAlex.
- Highlighting the Therapeutic Potential of an Underexplored Target: Human Dihydroorotate Dehydrogenase in Cancer, Rheumatoid Arthritis and Sclerosis.Current topics in medicinal chemistry · 2026Review
- The flexible chain: regulation of structure and activity of ETC complexes defines rate of ATP synthesis and sites of superoxide generation.Biophysical reviews · 2025Review
- Ferroptosis in pain: evidence, challenges, and opportunities.Frontiers in immunology · 2025Review
- Mitochondrion-Mediated Cell Death through Erk1-Alox5 Independent of Caspase-9 Signaling.Cells · 2022Article
- Expanding the Repertoire of Low-Molecular-Weight Pentafluorosulfanyl-Substituted Scaffolds.ChemMedChem · 2022Article
- Teriflunomide - The common drug with underestimated oxygen - Dependent anticancer potential.Biochemistry and biophysics reports · 2021Article
- Synthetic Retinoids as Potential Therapeutics in Prostate Cancer-An Update of the Last Decade of Research: A Review.International journal of molecular sciences · 2021Review
- The Mitochondria-Independent Cytotoxic Effect of Leflunomide on RPMI-8226 Multiple Myeloma Cell Line.Molecules (Basel, Switzerland) · 2021Article
- DHODH and cancer: promising prospects to be explored.Cancer & metabolism · 2021Review
- Fenretinide induces a new form of dynamin-dependent cell death in pediatric sarcoma.Cell death and differentiation · 2020Article
- Teriflunomide Does Not Change Dynamics of Nadph Oxidase Activation and Neuronal Dysfunction During Neuroinflammation.Frontiers in molecular biosciences · 2020Article
- Article
- Fenretinide-induced Apoptosis of Acute Myeloid Leukemia Cells via NR4A1 Translocation into Mitochondria and Bcl-2 Transformation.Journal of Cancer · 2019Article
- Inactivation/deficiency of DHODH induces cell cycle arrest and programed cell death in melanoma.Oncotarget · 2017Article
- Rare syndromes of the head and face: mandibulofacial and acrofacial dysostoses.Wiley interdisciplinary reviews. Developmental biology · 2017Review
- Multidrug resistance transporter-1 and breast cancer resistance protein protect against ovarian toxicity, and are essential in ovarian physiology.Reproductive toxicology (Elmsford, N.Y.) · 2017Article
- Review of the Genetic Basis of Jaw Malformations.Journal of pediatric genetics · 2016Review
- Novel insights into redox system and the mechanism of redox regulation.Molecular biology reports · 2016Review
- The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies.Oxidative medicine and cellular longevity · 2016Review
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) exhibits anticancer activity in vivo and triggers apoptosis in transformed cells in vitro. Thus, apoptosis induction is acknowledged as a mechanistic underpinning for 4HPR's cancer preventive and therapeutic effects. Apoptosis induction by 4HPR is routinely preceded by and dependent on the production of reactive oxygen species (ROS) in transformed cells. Very little evidence exists, outside the possible involvement of the mitochondrial electron transport chain or the plasma membrane NADPH oxidase complex, that would pinpoint the predominant site of 4HPR-induced ROS production in transformed cells. Here, we investigated the role of dihydroorotate dehydrogenase (DHODH; an enzyme associated with the mitochondrial electron transport chain and required for de novo pyrimidine synthesis) in 4HPR-induced ROS production and attendant apoptosis in transformed skin and prostate epithelial cells. In premalignant prostate epithelial cells and malignant cutaneous keratinocytes the suppression of DHODH activity by the chemical inhibitor teriflunomide or the reduction in DHODH protein expression by RNA interference markedly reduced 4HPR-induced ROS generation and apoptosis. Conversely, colon carcinoma cells that lacked DHODH expression were markedly resistant to the pro-oxidant and cytotoxic effects of 4HPR. Together, these results strongly implicate DHODH in 4HPR-induced ROS production and apoptosis.
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What OpenQuestion holds
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.