ArticleDrug design, development and therapy2014
Identification of a novel potential antitumor activity of gossypol as an APE1/Ref-1 inhibitor.
Article in Drug design, development and therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The trial behind it
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- A randomized, double-blind, placebo-controlled study of B-cell lymphoma 2 homology 3 mimetic gossypol combined with docetaxel and cisplatin for advanced non-small cell lung cancer with high expression of apurinic/apyrimidinic endonuclease 1.Investigational new drugs · 2020Trial
- Contrasting roles of APE1 and APE2 in genome maintenance, cancer development, and therapeutic targeting.NAR cancer · 2025Review
- Review
- Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons.Cells · 2023Review
- Bcl-2 pathway inhibition in solid tumors: a review of clinical trials.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Systematic Review of Gossypol/AT-101 in Cancer Clinical Trials.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment.International journal of molecular sciences · 2021Review
- 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
- Article
- Identification of small molecule enzyme inhibitors as broad-spectrum anthelmintics.Scientific reports · 2019Article
- APE1 stimulates EGFR-TKI resistance by activating Akt signaling through a redox-dependent mechanism in lung adenocarcinoma.Cell death & disease · 2018Article
- Article
- Small molecule activation of apurinic/apyrimidinic endonuclease 1 reduces DNA damage induced by cisplatin in cultured sensory neurons.DNA repair · 2016Article
- DNA repair targeted therapy: The past or future of cancer treatment?Pharmacology & therapeutics · 2016Review
- APE1-mediated DNA damage repair provides survival advantage for esophageal adenocarcinoma cells in response to acidic bile salts.Oncotarget · 2016Article
- 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
- Is redox signaling a feasible target for overcoming multidrug resistance in cancer chemotherapy?Frontiers in pharmacology · 2014Article
- Sequential treatment with AT-101 enhances cisplatin chemosensitivity in human non-small cell lung cancer cells through inhibition of apurinic/apyrimidinic endonuclease 1-activated IL-6/STAT3 signaling pathway.Drug design, development and therapy · 2014Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human apurinic/apyrimidinic endonuclease 1/redox enhancing factor-1 (APE1/Ref-1), an essential multifunctional protein involved in the repair of oxidative deoxyribonucleic acid (DNA) damage and transcriptional regulation, is often overexpressed in tumor tissues and cancer cells. Moreover, APE1/Ref-1 (APE1) overexpression has been linked to chemoresistance in human tumors. Thus, inhibiting APE1 function in cancer cells is considered a promising strategy to overcome resistance to therapeutic agents. Gossypol is a Bcl-2 homology 3 (BH3)-mimetic agent and is able to bind to the BH3 domain of B-cell lymphoma 2 (Bcl-2) family members. Other studies demonstrated that Bcl-2 directly interacted with APE1 via its BH domains. Using apurinic/apyrimidinic (AP) endonuclease assays, we found that gossypol inhibits the repair activity of APE1. Electrophoretic mobility shift assays and dual luciferase assays showed that gossypol could also inhibit the redox function of APE1. Using dual polarization interferometry technology, we show that gossypol can directly interact with APE1. Furthermore, addition of gossypol, in conjunction with APE1 overexpression, leads to cancer cell death. The addition of gossypol also enhances the cell killing effect of the laboratory alkylating agent methyl methanesulfonate and the clinical agent cisplatin (DDP). Administration of gossypol significantly inhibited the growth of xenografts. Furthermore, the combined treatment of gossypol and DDP resulted in a statistically higher antitumor activity compared with DDP alone in vivo. In conclusion, we have demonstrated that gossypol effectively inhibits the repair and redox activity of APE1 through a direct interaction.
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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.