ArticleNucleic acids research2014
A high-throughput chemical screen with FDA approved drugs reveals that the antihypertensive drug Spironolactone impairs cancer cell survival by inhibiting homology directed repair.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- Non-oncologic to oncologic drug: A systematic review of drug repurposing in cancer.Cancer chemotherapy and pharmacology · 2025Pooled it
- Tumor risks of finerenone in patients with type 2 diabetes mellitus complicated with chronic kidney disease: a meta-analysis and systematic review of randomized controlled trials.Frontiers in pharmacology · 2023Pooled it
- Proteomic Ligandability Maps of Spirocycle Acrylamide Stereoprobes Identify Covalent ERCC3 Degraders.Journal of the American Chemical Society · 2024Article
- Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.European heart journal · 2024Review
- Association of spironolactone use with risk of urinary tract cancer in the general population: A matched population-based cohort study.PloS one · 2024Article
- Identifying Suitable Reference Gene Candidates for Quantification of DNA Damage-Induced Cellular Responses in Human U2OS Cell Culture System.Biomolecules · 2023Article
- Review
- A Preclinical Study to Repurpose Spironolactone for Enhancing Chemotherapy Response in Bladder Cancer.Molecular cancer therapeutics · 2022Article
- Development of transgenic Daphnia magna for visualizing homology-directed repair of DNA.Scientific reports · 2022Article
- Novel Insights into the Role of the Mineralocorticoid Receptor in Human Glioblastoma.International journal of molecular sciences · 2021Article
- Topical Treatment of Human Skin and Cultured Keratinocytes with High-Dose Spironolactone Reduces XPB Expression and Induces Toxicity.JID innovations : skin science from molecules to population health · 2021Article
- Review
- Small-molecule drug repurposing to target DNA damage repair and response pathways.Seminars in cancer biology · 2021Review
- The Use of Antihypertensive Drugs as Coadjuvant Therapy in Cancer.Frontiers in oncology · 2021Review
- Spironolactone-induced XPB degradation requires TFIIH integrity and ubiquitin-selective segregase VCP/p97.Cell cycle (Georgetown, Tex.) · 2021Article
- Review
- Overcoming cancer therapeutic bottleneck by drug repurposing.Signal transduction and targeted therapy · 2020Review
- Spironolactone and XPB: An Old Drug with a New Molecular Target.Biomolecules · 2020Review
- Disease modeling and stem cell immunoengineering in regenerative medicine using CRISPR/Cas9 systems.Computational and structural biotechnology journal · 2020Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
DNA double-strand breaks (DSBs) are the most severe type of DNA damage. DSBs are repaired by non-homologous end-joining or homology directed repair (HDR). Identifying novel small molecules that affect HDR is of great importance both for research use and therapy. Molecules that elevate HDR may improve gene targeting whereas inhibiting molecules can be used for chemotherapy, since some of the cancers are more sensitive to repair impairment. Here, we performed a high-throughput chemical screen for FDA approved drugs, which affect HDR in cancer cells. We found that HDR frequencies are increased by retinoic acid and Idoxuridine and reduced by the antihypertensive drug Spironolactone. We further revealed that Spironolactone impairs Rad51 foci formation, sensitizes cancer cells to DNA damaging agents, to Poly (ADP-ribose) polymerase (PARP) inhibitors and cross-linking agents and inhibits tumor growth in xenografts, in mice. This study suggests Spironolactone as a new candidate for chemotherapy.
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Registered trials
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.