ArticleInvestigative ophthalmology & visual science2014
Suppression of choroidal neovascularization through inhibition of APE1/Ref-1 redox activity.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- APEX1-STAT3 signaling mediates the force-coordinated endothelial regeneration.Cellular and molecular life sciences : CMLS · 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
- Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons.Cells · 2023Review
- Beyond VEGF: Targeting Inflammation and Other Pathways for Treatment of Retinal Disease.The Journal of pharmacology and experimental therapeutics · 2023Review
- Identification of Novel Pathways Regulated by APE1/Ref-1 in Human Retinal Endothelial Cells.International journal of molecular sciences · 2023Article
- Drug Inhibition of Redox Factor-1 Restores Hypoxia-Driven Changes in Tuberous Sclerosis Complex 2 Deficient Cells.Cancers · 2022Article
- Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy.International journal of molecular sciences · 2021Review
- Review
- Fatty Acid Composition and Stoichiometry Determine the Angiogenesis Microenvironment.ACS omega · 2021Article
- The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease.Drug discovery today · 2021Review
- APE1/Ref-1 as a Novel Target for Retinal Diseases.Journal of cellular signaling · 2021Article
- AMP-Activated Protein Kinase Restricts Zika Virus Replication in Endothelial Cells by Potentiating Innate Antiviral Responses and Inhibiting Glycolysis.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Antitumor Activity and Mechanistic Characterization of APE1/Ref-1 Inhibitors in Bladder Cancer.Molecular cancer therapeutics · 2019Article
- Ref-1/APE1 Inhibition with Novel Small Molecules Blocks Ocular Neovascularization.The Journal of pharmacology and experimental therapeutics · 2018Article
- Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic.NPJ precision oncology · 2017Article
- Apurinic/apyrimidinic endonuclease 1 regulates angiogenesis in a transforming growth factor β-dependent manner in human osteosarcoma.Cancer science · 2015Article
- Small-molecule BH3 mimetic and pan-Bcl-2 inhibitor AT-101 enhances the antitumor efficacy of cisplatin through inhibition of APE1 repair and redox activity in non-small-cell lung cancer.Drug design, development and therapy · 2015Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
purposeThe redox function of APE1/Ref-1 is a key regulator in pathological angiogenesis, such as retinal neovascularization and tumor growth. In this study, we examined whether inhibition of APE1/Ref-1 redox function by a small molecule inhibitor E3330 suppresses experimental choroidal neovascularization (CNV) in vitro and in vivo.
methodsPrimate choroid endothelial cells (CECs) received treatment of 0 to 100 μM E3330 alone or cotreatment of E3330 and 500 μg/mL anti-VEGF antibody bevacizumab. Choroid endothelial cell angiogenic function was examined by cell proliferation, migration, and tube formation assays. The effects of E3330 on NF-κB and STAT3 signaling pathways were determined by reporter gene assay, Western blot, and ELISA. Laser-induced CNV mouse model was used to test the effects of E3330 in vivo. Potential toxicity of E3330 was evaluated by TUNEL assay.
resultsThe E3330 of 25 to 100 μM dose-dependently suppressed CEC proliferation, migration, and tube formation, in the absence of noticeable cell toxicity. Lower doses of E3330 (10-20 μM) reduced the transcriptional activity of NF-κB and STAT3 without affecting protein phosphorylation of both molecules. At the same time, E3330 downregulated MCP-1 production in CECs. The antiangiogenic effect of E3330 was comparable and additive to bevacizumab. The E3330 effectively attenuated the progression of laser-induced CNV in mice after a single intravitreal injection.
conclusionsThe APE1/Ref-1 redox function regulates multiple transcription factors and inflammatory molecules, and is essential for CEC angiogenesis. Specific inhibition of APE1/Ref-1 redox function with E3330 may represent a promising novel treatment for wet AMD.
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