ArticleCell death & disease2021
Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 124 citations in OpenAlex.
- APE1/Ref-1: multifunctional biology, selective inhibition, and the path to clinical translation.Expert opinion on therapeutic targets · 2026Review
- APE1 inhibition-promoted pyroptosis triggers T-cell infiltration and enhances anti-tumor immunity in NSCLC.Genes & diseases · 2026Article
- Orchestrated metal ion repositioning defines the dynamic catalytic strategy of the essential DNA repair nuclease APE1.bioRxiv : the preprint server for biology · 2026Article
- Targeting the APE1 hub: integrating DNA repair and redox signaling for precision management of inflammation-associated diseases.Molecular biology reports · 2026Review
- Acquired resistance of cancer therapies: Mechanisms and perspectives.Chinese medical journal · 2026Review
- Multiple programmed cell death patterns predict the prognosis and therapeutic sensitivity in head and neck squamous cell carcinoma.Discover oncology · 2026Article
- The Role of Traditional Chinese Medicine in Acute Lung Injury: Targeting Programmed Cell Death.Drug design, development and therapy · 2026Review
- Functions and applications of enzymes in nucleic acid nanotechnology.Journal of nanobiotechnology · 2025Review
- Contrasting roles of APE1 and APE2 in genome maintenance, cancer development, and therapeutic targeting.NAR cancer · 2025Review
- Oxymatrine attenuates pulmonary fibrosis via APE1‑mediated regulation of the PINK1/Parkin pathway.Molecular medicine reports · 2025Article
- Caspase-independent cell death in lung cancer: from mechanisms to clinical applications.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- APEX1 Knockdown Alleviates Inflammation and Fibrosis in Myocardial Infarction Through Promoting ZCCHC9 Expression and Blocking the p38 MAPK Signaling.Biochemical genetics · 2025Article
- Integrative assessment of RNA sequencing and in silico analysis to pinpoint mRNAs, lncRNAs, and circRNAs interactions with miRNAs underlying arsenic-induced neurotoxicity.BMC genomics · 2025Article
- Teniposide Triggers DNA Repair Inhibition by Binding and Ubiquitination of Apurinic/Apyrimidinic Endonuclease 1 to Boost Oxidative DNA Damage for Lung Cancer Destruction.ACS pharmacology & translational science · 2025Article
- Explainable AI-driven prediction of APE1 inhibitors: enhancing cancer therapy with machine learning models and feature importance analysis.Molecular diversity · 2025Article
- APE1 promotes lung adenocarcinoma through G4-mediated transcriptional reprogramming of urea cycle metabolism.iScience · 2025Article
- Significance of serum APE1-AAbs, PTX-3, and miR-486-3p in patients with colorectal cancer undergoing radical surgery.World journal of gastrointestinal oncology · 2025Article
- Triggering Pyroptosis in Cancer.Biomolecules · 2025Review
- Ferulic Acid Regulates GSDMD through the ROS/JNK/Bax Mitochondrial Apoptosis Pathway to Induce Pyroptosis in Lung Cancer.Current pharmaceutical biotechnology · 2025Article
- RNA-seq analysis reveals key genes associated with downregulation of APE1 in esophageal squamous cell carcinoma.Frontiers in genetics · 2025Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apurinic/apyrimidinic endonuclease 1 (APE1) plays a critical role in the base excision repair (BER) pathway, which is responsible for the excision of apurinic sites (AP sites). In non-small cell lung cancer (NSCLC), APE1 is highly expressed and associated with poor patient prognosis. The suppression of APE1 could lead to the accumulation of unrepaired DNA damage in cells. Therefore, APE1 is viewed as an important marker of malignant tumors and could serve as a potent target for the development of antitumor drugs. In this study, we performed a high-throughput virtual screening of a small-molecule library using the three-dimensional structure of APE1 protein. Using the AP site cleavage assay and a cell survival assay, we identified a small molecular compound, NO.0449-0145, to act as an APE1 inhibitor. Treatment with NO.0449-0145 induced DNA damage, apoptosis, pyroptosis, and necroptosis in the NSCLC cell lines A549 and NCI-H460. This inhibitor was also able to impede cancer progression in an NCI-H460 mouse model. Moreover, NO.0449-0145 overcame both cisplatin- and erlotinib-resistance in NSCLC cell lines. These findings underscore the importance of APE1 as a therapeutic target in NSCLC and offer a paradigm for the development of small-molecule drugs that target key DNA repair proteins for the treatment of NSCLC and other cancers.
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