ArticleCells2020
Nobiletin Promotes Megakaryocytic Differentiation through the MAPK/ERK-Dependent EGR1 Expression and Exerts Anti-Leukemic Effects in Human Chronic Myeloid Leukemia (CML) K562 Cells.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- Chromosomal Heterogeneity and Enrichment of Mitotic Regulatory Programs Reveal a Therapeutic Vulnerability in Cytarabine-Resistant FLT3-ITD AML.Current issues in molecular biology · 2026Article
- Synthesis of redox-responsive polyurethane nanocapsules for small-molecule delivery and antitumor evaluation on human leukemia K562 cells.Molecular diversity · 2026Article
- MicroRNA-181a in acute lymphoblastic leukemia: expression pattern, target genes and its potential as a biomarker.Biochemistry and biophysics reports · 2026Review
- Mechanisms of Antiproliferative Effects of Nobiletin, Scoparone, and Tangeretin Isolated fromInternational journal of molecular sciences · 2026Article
- Illuminating photoreceptors: TGFβ signaling modulates the severeness of retinal degeneration.Cell death discovery · 2025Article
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- Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review.Molecules (Basel, Switzerland) · 2025Review
- The up-regulation of TGF-β1 by miRNA-132-3p/WT1 is involved in inducing leukemia cells to differentiate into macrophages.PloS one · 2025Article
- Flavonoids as Chemosensitizers in Leukemias.Advances in experimental medicine and biology · 2025Review
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- Conditioned Medium Derived From Human Dental Follicle Mesenchymal Stem Cells Alleviates Macrophage Proinflammatory Responses Through MAPK-ERK-EGR1 Axis.Stem cells international · 2024Article
- The Application of Ethnomedicine in Modulating Megakaryocyte Differentiation and Platelet Counts.International journal of molecular sciences · 2023Review
- Inhibition of the MAPK/c-Jun-EGR1 Pathway Decreases Photoreceptor Cell Death in theInternational journal of molecular sciences · 2022Article
- The Citrus Flavonoid Nobiletin Downregulates Angiopoietin-like Protein 3 (ANGPTL3) Expression and Exhibits Lipid-Modulating Effects in Hepatic Cells and Adult Zebrafish Models.International journal of molecular sciences · 2022Article
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- miR-let-7c-3p targeting on Egr-1 contributes to the committed differentiation of leukemia cells into monocyte/macrophages.Oncology letters · 2022Article
- 5-Demethylnobiletin Inhibits Cell Proliferation, Downregulates ID1 Expression, Modulates the NF-κB/TNF-α Pathway and Exerts Antileukemic Effects in AML Cells.International journal of molecular sciences · 2022Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Differentiation therapy is an alternative strategy used to induce the differentiation of blast cells toward mature cells and to inhibit tumor cell proliferation for cancer treatment. Nobiletin (NOB), a polymethoxyflavone phytochemical, is present abundantly in citrus peels and has been reported to possess anti-cancer activity. In this study, we investigated the anti-leukemic effects of NOB on cell differentiation and its underlying mechanisms in human chronic myeloid leukemia (CML) K562 cells. NOB (100 μM) treatment for 24 and 48 h significantly decreased viability of K562 cells to 54.4 ± 5.3% and 46.2 ± 9.9%, respectively. NOB (10-100 μM) significantly inhibited cell growth in K562 cells. Flow cytometry analysis and immunoblotting data showed that NOB (40 and 80 μM) could modulate the cell cycle regulators including p21, p27, and cyclin D2, and induce G1 phase arrest. NOB also increased the messenger RNA (mRNA) and protein expression of megakaryocytic differentiation markers, such as CD61, CD41, and CD42 as well as the formation of large cells with multi-lobulated nuclei in K562 cells. These results suggested that NOB facilitated K562 cells toward megakaryocytic differentiation. Furthermore, microarray analysis showed that expression of EGR1, a gene associated with promotion of megakaryocytic differentiation, was markedly elevated in NOB-treated K562 cells. The knockdown of EGR1 expression by small interference RNA (siRNA) could significantly attenuate NOB-mediated cell differentiation. We further elucidated that NOB induced EGR1 expression and CD61 expression through increases in MAPK/ERK phosphorylation in K562 cells. These results indicate that NOB promotes megakaryocytic differentiation through the MAPK/ERK pathway-dependent EGR1 expression in human CML cells. In addition, NOB when combined with imatinib could synergistically reduce the viability of K562 cells. Our findings suggest that NOB may serve as a beneficial anti-leukemic agent for differentiation therapy.
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