ArticlePloS one2012
Tetrahydrouridine inhibits cell proliferation through cell cycle regulation regardless of cytidine deaminase expression levels.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Cytidine Deaminase Resolves Replicative Stress and Protects Pancreatic Cancer from DNA-Targeting Drugs.Cancer research · 2024Article
- A new technique for the analysis of metabolic pathways of cytidine analogues and cytidine deaminase activities in cells.Scientific reports · 2023Article
- Upregulation of cytidine deaminase in NAT1 knockout breast cancer cells.Journal of cancer research and clinical oncology · 2023Article
- microRNAs Associated with Gemcitabine Resistance via EMT, TME, and Drug Metabolism in Pancreatic Cancer.Cancers · 2023Review
- Cytidine deaminase can deaminate fused pyrimidine ribonucleosides.Organic & biomolecular chemistry · 2021Article
- A Metabolomics Study of Serum in Hospitalized Patients With Chronic Schizophrenia.Frontiers in psychiatry · 2021Article
- Intracellular Cytidine Deaminase Regulates Gemcitabine Metabolism in Pancreatic Cancer Cell Lines.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- The Emerging Role of Cytidine Deaminase in Human Diseases: A New Opportunity for Therapy?Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Antitumor Research of the Active Ingredients from Traditional Chinese Medical Plant Polygonum Cuspidatum.Evidence-based complementary and alternative medicine : eCAM · 2018Review
- CDA gene silencing regulated the proliferation and apoptosis of chronic myeloid leukemia K562 cells.Cancer cell international · 2018Article
- Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs.Chemical reviews · 2016Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tetrahydrouridine (THU) is a well characterized and potent inhibitor of cytidine deaminase (CDA). Highly expressed CDA catalyzes and inactivates cytidine analogues, ultimately contributing to increased gemcitabine resistance. Therefore, a combination therapy of THU and gemcitabine is considered to be a potential and promising treatment for tumors with highly expressed CDA. In this study, we found that THU has an alternative mechanism for inhibiting cell growth which is independent of CDA expression. Three different carcinoma cell lines (MIAPaCa-2, H441, and H1299) exhibited decreased cell proliferation after sole administration of THU, while being unaffected by knocking down CDA. To investigate the mechanism of THU-induced cell growth inhibition, cell cycle analysis using flow cytometry was performed. This analysis revealed that THU caused an increased rate of G1-phase occurrence while S-phase occurrence was diminished. Similarly, Ki-67 staining further supported that THU reduces cell proliferation. We also found that THU regulates cell cycle progression at the G1/S checkpoint by suppressing E2F1. As a result, a combination regimen of THU and gemcitabine might be a more effective therapy than previously believed for pancreatic carcinoma since THU works as a CDA inhibitor, as well as an inhibitor of cell growth in some types of pancreatic carcinoma cells.
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