ArticleOncotarget2017
Thymoquinone exerts potent growth-suppressive activity on leukemia through DNA hypermethylation reversal in leukemia cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The trial behind it
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Who cites it
32 citing papers in PubMed, 67 citations in OpenAlex.
- Epigenetic Reactivation of <italic>SOCS-3</italic> and Inhibition of ERK1/2 Underlie Thymoquinone-Induced Apoptosis in a Chronic Myeloid Leukemia Xenograft Model.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026Article
- Epigenetic Targeting in Myeloid Malignancies.Advances in experimental medicine and biology · 2026Review
- Targeting Cancer Through Thymoquinone: From Molecular Mechanisms to Clinical Prospects.International journal of molecular sciences · 2025Review
- CD133-Guided RNA Nanoparticle Delivery of FTO siRNA Impairs Leukemia Resistance to Tyrosine Kinase Inhibitor Therapy.RNA nanomed · 2025Article
- In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1.Molecules (Basel, Switzerland) · 2024Article
- Management of triple-negative breast cancer by natural compounds through different mechanistic pathways.Frontiers in genetics · 2024Review
- Recent Advances in Natural Products with Anti-Leukemia and Anti- Lymphoma Activities.Mini reviews in medicinal chemistry · 2024Review
- Thymoquinone Enhances Apoptosis of K562 Chronic Myeloid Leukemia Cells through Hypomethylation ofPharmaceuticals (Basel, Switzerland) · 2023Article
- Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.Signal transduction and targeted therapy · 2023Review
- Response of Skin-Derived and Metastatic Human Malignant Melanoma Cell Lines to Thymoquinone and Thymoquinone-Loaded Liposomes.Pharmaceutics · 2022Article
- Thymoquinone Inhibits JAK/STAT and PI3K/Akt/ mTOR Signaling Pathways in MV4-11 and K562 Myeloid Leukemia Cells.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Thymoquinone upregulates IL17RD in controlling the growth and metastasis of triple negative breast cancer cells in vitro.BMC cancer · 2022Article
- The Potential Role ofMolecules (Basel, Switzerland) · 2022Article
- Gene Expression Profiling and Protein Analysis Reveal Suppression of the C-Myc Oncogene and Inhibition JAK/STAT and PI3K/AKT/mTOR Signaling by Thymoquinone in Acute Myeloid Leukemia Cells.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Advances in research on the relationship between thymoquinone and pancreatic cancer.Frontiers in oncology · 2022Review
- Metformin and Thymoquinone Synergistically Inhibit Proliferation of Imatinib-Resistant Human Leukemic Cells.Frontiers in pharmacology · 2022Article
- Thymoquinone Inhibits Growth of Acute Myeloid Leukemia Cells through ReversalPharmaceuticals (Basel, Switzerland) · 2021Article
- Natural Bioactive Compounds Targeting Epigenetic Pathways in Cancer: A Review on Alkaloids, Terpenoids, Quinones, and Isothiocyanates.Nutrients · 2021Review
- Targeting microRNAs with thymoquinone: a new approach for cancer therapy.Cellular & molecular biology letters · 2021Review
- Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis.Pharmaceutics · 2021Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Thymoquinone (TQ), a bioactive constituent of the volatile oil of Monarda fistulosa and Nigella sativa, possesses cancer-specific growth inhibitory effects, but the underlying molecular mechanisms remain largely elusive. We propose that TQ curbs cancer cell growth through dysfunction of DNA methyltransferase 1 (DNMT1). Molecular docking analysis revealed that TQ might interact with the catalytic pocket of DNMT1 and compete with co-factor SAM/SAH for DNMT1 inhibition. In vitro inhibitory assays showed that TQ decreases DNMT1 methylation activity in a dose-dependent manner with an apparent IC50 of 30 nM. Further, exposure of leukemia cell lines and patient primary cells to TQ resulted in DNMT1 downregulation, mechanistically, through dissociation of Sp1/NFkB complex from DNMT1 promoter. This led to a reduction of DNA methylation, a decrease of colony formation and an increase of cell apoptosis via the activation of caspases. In addition, we developed and validated a sensitive and specific LC-MS/MS method and successfully detected a dynamic change of TQ in mouse plasma after administration of TQ through the tail vein, and determined a tolerable dose of TQ to be 15 mg/kg in mouse. TQ administration into leukemia-bearing mice induced leukemia regression, as indicated by the reversed splenomegaly and the inhibited leukemia cell growth in lungs and livers. Our study for the first time demonstrates that DNMT1-dependent DNA methylation mediates the anticancer actions of TQ, opening a window to develop TQ as a novel DNA hypomethylating agent for leukemia therapy.
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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.