ArticleCancer science2009
The oral iron chelator deferasirox represses signaling through the mTOR in myeloid leukemia cells by enhancing expression of REDD1.
Article in Cancer science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61 citing papers in PubMed, 133 citations in OpenAlex.
- Inhibition of SLC11A1-Mediated Lysosomal Iron Accumulation in Microglia Promotes Repair Following White Matter Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dual Impact of Iron Deficiency and Antibiotics on Host Metabolism: A Tissue-Level Analysis.Metabolites · 2025Article
- Review
- Deferasirox improved iron homeostasis and hematopoiesis in ovariectomized rats with iron accumulation.Scientific reports · 2025Article
- Identification and overcoming rituximab resistance in diffuse large B-cell lymphoma using next-generation sequencing.The Korean journal of internal medicine · 2023Article
- The stress-responsive protein REDD1 and its pathophysiological functions.Experimental & molecular medicine · 2023Review
- Mechanistic target of rapamycin (mTOR) regulates self-sustained quiescence, tumor indolence, and late clinical metastasis in a Beclin-1-dependent manner.Cell cycle (Georgetown, Tex.) · 2023Article
- Chrysophanol Suppresses Cell Growth via mTOR/PPAR-α Regulation and ROS Accumulation in Cultured Human Tongue Squamous Carcinoma SAS Cells.Current issues in molecular biology · 2022Article
- Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?International journal of molecular sciences · 2021Review
- Ceruloplasmin correlates with immune infiltration and serves as a prognostic biomarker in breast cancer.Aging · 2021Article
- New Insights into Red Blood Cell Microcytosis upon mTOR Inhibitor Administration.International journal of molecular sciences · 2021Article
- TOR functions as a molecular switch connecting an iron cue with host innate defense against bacterial infection.PLoS genetics · 2021Article
- Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Crosstalk between Macrophages, T Cells, and Iron Metabolism in Tumor Microenvironment.Oxidative medicine and cellular longevity · 2021Review
- Protein Carbonylation and Lipid Peroxidation in Hematological Malignancies.Antioxidants (Basel, Switzerland) · 2020Review
- Deferasirox-Dependent Iron Chelation Enhances Mitochondrial Dysfunction and Restores p53 Signaling by Stabilization of p53 Family Members in Leukemic Cells.International journal of molecular sciences · 2020Article
- Genome-wide transcriptomics leads to the identification of deregulated genes after deferasirox therapy in low-risk MDS patients.The pharmacogenomics journal · 2020Article
- Deferasirox, an iron-chelating agent, alleviates acute lung inflammation by inhibiting neutrophil activation and extracellular trap formation.The Journal of international medical research · 2020Article
- Invasion inhibition in pancreatic cancer using the oral iron chelating agent deferasirox.BMC cancer · 2020Article
- Iron chelation inhibits mTORC1 signaling involving activation of AMPK and REDD1/Bnip3 pathways.Oncogene · 2020Article
1 more citing papers are in PubMed but not listed here.
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6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
To evaluate the effect of deferasirox in human myeloid leukemia cells, and to identify the molecular pathways responsible for antiproliferative effects on leukemia cells during chelation therapy, we performed gene expression profiling to focus on the pathway involved in the anticancer effect of deferasirox. The inhibitory concentration (IC50) of deferasirox was 17-50 microM in three human myeloid cell lines (K562, U937, and HL60), while those in fresh leukemia cells obtained from four patients it varied from 88 to 172 microM. Gene expression profiling using Affymerix GeneChips (U133 Plus 2.0) revealed up-regulation of cyclin-dependent kinase inhibitor 1A (CDKN1A) encoding p21CIP, genes regulating interferon (i.e. IFIT1). Pathways related to iron metabolism and hypoxia such as growth differentiation factor 15 (GDF-15) and Regulated in development and DNA damage response (REDD1) were also prominent. Based on the results obtained from gene expression profiling, we particularly focused on the REDD1/mTOR (mammalian target of rapamycin) pathway in deferasirox-treated K562 cells, and found an enhanced expression of REDD1 and its down-stream protein, tuberin (TSC2). Notably, S6 ribosomal protein as well as phosphorylated S6, which is known to be a target of mTOR, was significantly repressed in deferasirox-treated K562 cells, and REDD1 small interfering RNA restored phosphorylation of S6. Although iron chelation may affect multiple signaling pathways related to cell survival, our data support the conclusion that REDD1 functions up-stream of tuberin to down-regulate the mTOR pathway in response to deferasirox. Deferasirox might not only have benefit for iron chelation but also may be an antiproliferative agent in some myeloid leukemias, especially patients who need both iron chelation and reduction of leukemia cells.
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