ArticleMolecular cancer therapeutics2008
Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migration.
Article in Molecular cancer therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 123 citations in OpenAlex.
- Contrasting roles of APE1 and APE2 in genome maintenance, cancer development, and therapeutic targeting.NAR cancer · 2025Review
- Base excision repair within structure-forming repeat sequences and its impact on cancer and other diseases.NAR cancer · 2025Review
- Personalized prediction of anticancer potential of non-oncology drugs through learning from genome derived molecular pathways.NPJ precision oncology · 2025Article
- Targeting APE1: Advancements in the Diagnosis and Treatment of Tumors.Protein and peptide letters · 2025Review
- Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review).Molecular and clinical oncology · 2024Review
- The APE1/REF-1 and the hallmarks of cancer.Molecular biology reports · 2024Review
- The inhibitor of the redox activity of APE1/REF-1, APX2009, reduces the malignant phenotype of breast cancer cells.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- APE1/Ref-1 as a Therapeutic Target for Inflammatory Bowel Disease.Biomolecules · 2023Review
- Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons.Cells · 2023Review
- Article
- Targeting Polymerase Theta (POLθ) for Cancer Therapy.Cancer treatment and research · 2023Review
- APEX1 predicts poor prognosis of gallbladder cancer and affects biological properties of CD133Journal of Cancer · 2023Article
- APE1 assembles biomolecular condensates to promote the ATR-Chk1 DNA damage response in nucleolus.Nucleic acids research · 2022Article
- Bis-Cinnamamide Derivatives as APE/Ref-1 Inhibitors for the Treatment of Human Melanoma.Molecules (Basel, Switzerland) · 2022Article
- The human AP-endonuclease 1 (APE1) is a DNA G-quadruplex structure binding protein and regulates KRAS expression in pancreatic ductal adenocarcinoma cells.Nucleic acids research · 2022Article
- Pharmacological inhibition of Ref-1 enhances the therapeutic sensitivity of papillary thyroid carcinoma to vemurafenib.Cell death & disease · 2022Article
- Potential Role of APEX1 During Ferroptosis.Frontiers in oncology · 2022Review
- APE1/Ref-1 Role in Inflammation and Immune Response.Frontiers in immunology · 2022Review
- Inhibiting the redox function of APE1 suppresses cervical cancer metastasis via disengagement of ZEB1 from E-cadherin in EMT.Journal of experimental & clinical cancer research : CR · 2021Article
- Role of Reductive versus Oxidative Stress in Tumor Progression and Anticancer Drug Resistance.Cells · 2021Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
AP endonuclease 1 (APE1; also known as REF-1) contains a DNA repair domain and a redox regulation domain. APE1 is overexpressed in several human cancers, and disruption of APE1 function has detrimental effects on cancer cell viability. However, the selective contribution of the redox and the DNA repair domains to maintenance of cellular homeostasis in cancer has not been elucidated. In the present study, we used E3330, a small-molecule inhibitor of APE1 redox domain function, to interrogate the functional relevance of sustained redox function in pancreatic cancer. We show that E3330 significantly reduces the growth of human pancreatic cancer cells in vitro. This phenomenon was further confirmed by a small interfering RNA experiment to knockdown APE1 expression in pancreatic cancer cells. Further, the growth-inhibitory effects of E3330 are accentuated by hypoxia, and this is accompanied by striking inhibition in the DNA-binding ability of hypoxia-inducible factor-1alpha, a hypoxia-induced transcription factor. E3330 exposure promotes endogenous reactive oxygen species formation in pancreatic cancer cells, and the resulting oxidative stress is associated with higher levels of oxidized, and hence inactive, SHP-2, an essential protein tyrosine phosphatase that promotes cancer cell proliferation in its active state. Finally, E3330 treatment inhibits pancreatic cancer cell migration as assessed by in vitro chemokine assays. E3330 shows anticancer properties at multiple functional levels in pancreatic cancer, such as inhibition of cancer cell growth and migration. Inhibition of the APE1 redox function through pharmacologic means has the potential to become a promising therapeutic strategy in this disease.
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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.