ArticleiScience2021
Mitochondria-targeted hydroxyurea inhibits OXPHOS and induces antiproliferative and immunomodulatory effects.
Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed.
- The application of nanotechnology in regulating mitochondrial function in tumor microenvironment for cancer therapy.Theranostics · 2026Review
- Anticancer potential of 2,2'-bipyridine hydroxamic acid derivatives in head and neck cancer therapy.Journal of computer-aided molecular design · 2025Article
- Article
- Mitochondria-targeted strategies in tumor immunity.Frontiers in immunology · 2025Review
- Metabolic regulation of myeloid-derived suppressor cells in tumor immune microenvironment: targets and therapeutic strategies.Theranostics · 2025Review
- New Insights into Aspirin's Anticancer Activity: The Predominant Role of Its Iron-Chelating Antioxidant Metabolites.Antioxidants (Basel, Switzerland) · 2024Review
- Enhanced T cell immune activity mediated by Drp1 promotes the efficacy of PD-1 inhibitors in treating lung cancer.Cancer immunology, immunotherapy : CII · 2024Article
- Mitochondrial regulation in the tumor microenvironment: targeting mitochondria for immunotherapy.Frontiers in immunology · 2024Review
- Review
- Redox-crippled MitoQ potently inhibits breast cancer and glioma cell proliferation: A negative control for verifying the antioxidant mechanism of MitoQ in cancer and other oxidative pathologies.Free radical biology & medicine · 2023Article
- Antiproliferative effects of mitochondria-targeted N-acetylcysteine and analogs in cancer cells.Scientific reports · 2023Article
- The mechanisms of action of mitochondrial targeting agents in cancer: inhibiting oxidative phosphorylation and inducing apoptosis.Frontiers in pharmacology · 2023Review
- Article
- New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer.International journal of molecular sciences · 2022Review
- Mitofusins: from mitochondria to fertility.Cellular and molecular life sciences : CMLS · 2022Review
- Exploiting the tumor immune microenvironment and immunometabolism using mitochondria-targeted drugs: Challenges and opportunities in racial disparity and cancer outcome research.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Review
- Combining PEGylated mito-atovaquone with MCT and Krebs cycle redox inhibitors as a potential strategy to abrogate tumor cell proliferation.Scientific reports · 2022Article
- Reactive oxygen species, proinflammatory and immunosuppressive mediators induced in COVID-19: overlapping biology with cancer.RSC chemical biology · 2021Review
- Cellular and Exosomal Regulations of Sepsis-Induced Metabolic Alterations.International journal of molecular sciences · 2021Review
- OXPHOS-targeting drugs in oncology: new perspectives.Expert opinion on therapeutic targetsReview
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Hydroxyurea (HU), an FDA-approved drug for treating sickle cell disease, is used as an antitumor drug alone and together with conventional chemotherapeutics or radiation therapy. HU is used primarily to treat myeloproliferative diseases because it inhibits the enzyme ribonucleotide reductase involved in DNA synthesis. The hydroxyl group in HU is considered critical for its antiproliferative and chemotherapeutic effects. Here, we substituted the hydroxyl group in HU with a triphenylphosphonium cation attached to an alkyl group with different chain lengths, forming a new class of mitochondria-targeted HU (Mito-HU). Elongating the alkyl side chain length increased the hydrophobicity of Mito-HUs, inhibition of oxidative phosphorylation, and antiproliferative effects in tumor cells. Both mitochondrial complex I- and complex III-induced oxygen consumption decreased with the increasing hydrophobicity of Mito-HUs. The more hydrophobic Mito-HUs also potently inhibited the monocytic myeloid-derived suppressor cells and suppressive neutrophils, and stimulated T cell response, implicating their potential antitumor immunomodulatory mechanism.
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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.