ArticleExperimental hematology2010
Inhibition of the redox function of APE1/Ref-1 in myeloid leukemia cell lines results in a hypersensitive response to retinoic acid-induced differentiation and apoptosis.
Article in Experimental hematology, 2010. 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, 46 citations in OpenAlex.
- Ref-1 redox activity modulates canonical Wnt signaling in endothelial cells.Redox biology · 2025Article
- APEX1 Polymorphisms Affect Acute Myeloid Leukemia Risk, and Its Expression Is Involved in Cell Proliferation and Differentiation.International journal of laboratory hematology · 2025Article
- Ref-1 redox activity regulates retinal neovascularization by modulating transcriptional activation of HIF-1α.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.Angiogenesis · 2025Article
- Beyond VEGF: Targeting Inflammation and Other Pathways for Treatment of Retinal Disease.The Journal of pharmacology and experimental therapeutics · 2023Review
- Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy.International journal of molecular sciences · 2021Review
- Ref-1 redox activity alters cancer cell metabolism in pancreatic cancer: exploiting this novel finding as a potential target.Journal of experimental & clinical cancer research : CR · 2021Article
- Chemical Inhibition of Apurinic-Apyrimidinic Endonuclease 1 Redox and DNA Repair Functions Affects the Inflammatory Response via Different but Overlapping Mechanisms.Frontiers in cell and developmental biology · 2021Article
- APE1/Ref-1 as a Novel Target for Retinal Diseases.Journal of cellular signaling · 2021Article
- Cleavage of the APE1 N-Terminal Domain in Acute Myeloid Leukemia Cells Is Associated with Proteasomal Activity.Biomolecules · 2020Article
- Base Excision Repair in the Immune System: Small DNA Lesions With Big Consequences.Frontiers in immunology · 2020Review
- Exposure of Barrett's and esophageal adenocarcinoma cells to bile acids activates EGFR-STAT3 signaling axis via induction of APE1.Oncogene · 2018Article
- Ref-1/APE1 Inhibition with Novel Small Molecules Blocks Ocular Neovascularization.The Journal of pharmacology and experimental therapeutics · 2018Article
- Reactive oxygen species in haematopoiesis: leukaemic cells take a walk on the wild side.Journal of experimental & clinical cancer research : CR · 2018Review
- DNA repair after oxidative stress: current challenges.Current opinion in toxicology · 2018Article
- APE1/Ref-1 knockdown in pancreatic ductal adenocarcinoma - characterizing gene expression changes and identifying novel pathways using single-cell RNA sequencing.Molecular oncology · 2017Article
- Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic.NPJ precision oncology · 2017Article
- Regulation of HIF1α under Hypoxia by APE1/Ref-1 Impacts CA9 Expression: Dual Targeting in Patient-Derived 3D Pancreatic Cancer Models.Molecular cancer therapeutics · 2016Article
- Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) redox function negatively regulates NRF2.The Journal of biological chemistry · 2015Article
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Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveThe standard of care for promyelocytic leukemia includes use of the differentiating agent all-trans retinoic acid (RA) and chemotherapy. RA induces cell differentiation through retinoic acid receptor (RAR) transcription factors. Because redox mechanisms influence how readily transcription factors bind to DNA response elements (RARE), the impact of small molecule (E3330) inhibition of the redox regulatory protein, apurinic-apyrimidinic endonuclease/redox effector factor (APE1/Ref-1) on RAR DNA binding and function in RA-induced myeloid leukemia cell differentiation and apoptosis was investigated. MATERIALS AND
methodsThe redox function of APE1 was studied using the small molecule inhibitor E3330 in HL-60 and PLB acute myeloid leukemia cells. Electrophoretic mobility shift assays were employed to determine effect of inhibitor on APE1/Ref-1 redox signaling function. Trypan blue assays, Annexin-V/propidium iodide and CD11b staining, and real-time polymerase chain reaction analyses were employed to determine survival, apoptosis, and differentiation status of cells in culture.
resultsRARα binds to its RARE in a redox-dependent manner mediated by APE1/Ref-1 redox regulation. Redox-dependent RAR-RARE binding is blocked by E3330, a small molecule redox inhibitor of APE1/Ref-1. Combination treatment of RA + E3330 results in a profound hypersensitivity of myeloid leukemia cells to RA-induced differentiation and apoptosis. Additionally, redox inhibition by E3330 results in enhanced RAR target gene, BLR-1, expression in myeloid leukemia cells.
conclusionsThe redox function of APE1/Ref-1 regulates RAR binding to its DNA RAREs influencing the response of myeloid leukemia cells to RA-induced differentiation. Targeting of APE1/Ref-1 redox function may allow manipulation of the retinoid response with therapeutic implications.
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