ArticleThe Journal of investigative dermatology2019
Spironolactone Depletes the XPB Protein and Inhibits DNA Damage Responses in UVB-Irradiated Human Skin.
Article in The Journal of investigative dermatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 28 citations in OpenAlex.
- Integrating Structural, Biochemical, and Cellular Perspectives on the TFIIH Helicases XPB and XPD.Biomolecules · 2026Review
- Development of a competitive immunoassay platform for quantifying the oligonucleotide products of nucleotide excision repair in UV-irradiated cells.Nucleic acids research · 2026Article
- Direct aldosterone stimulation of skeletal muscle fibroblasts changes gene expression and differentially affects fibroblast functions from normal and diseased muscles.Frontiers in physiology · 2026Article
- Review
- Treatment of human cells with the anti-cancer drug cisplatin results in the caspase-dependent release of adduct-containing cell-free DNA.DNA repair · 2025Article
- Clinical Properties and Non-Clinical Testing of Mineralocorticoid Receptor Antagonists in In Vitro Cell Models.International journal of molecular sciences · 2024Review
- The Microbiome and Acne: Perspectives for Treatment.Dermatology and therapy · 2024Review
- DNA Containing Cyclobutane Pyrimidine Dimers Is Released from UVB-Irradiated Keratinocytes in a Caspase-Dependent Manner.The Journal of investigative dermatology · 2022Article
- Mineralocorticoid receptor antagonist treatment of established pulmonary arterial hypertension improves interventricular dependence in the SU5416-hypoxia rat model.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- XPA is susceptible to proteolytic cleavage by cathepsin L during lysis of quiescent cells.DNA repair · 2022Article
- 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
- Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment.International journal of molecular sciences · 2021Review
- Review
- Inhibitors of Nucleotide Excision Repair Decrease UVB-Induced Mutagenesis-An In Vitro Study.International journal of molecular sciences · 2021Article
- Spironolactone-induced XPB degradation requires TFIIH integrity and ubiquitin-selective segregase VCP/p97.Cell cycle (Georgetown, Tex.) · 2021Article
- Role of Nucleotide Excision Repair in Cisplatin Resistance.International journal of molecular sciences · 2020Review
- Insulin-like Growth Factor-1 Impacts p53 Target Gene Induction in UVB-irradiated Keratinocytes and Human Skin.Photochemistry and photobiology · 2020Article
- Spironolactone and XPB: An Old Drug with a New Molecular Target.Biomolecules · 2020Review
- Detection of the small oligonucleotide products of nucleotide excision repair in UVB-irradiated human skin.DNA repair · 2020Article
- ATR Kinase Activity Limits Mutagenesis and Promotes the Clonogenic Survival of Quiescent Human Keratinocytes Exposed to UVB Radiation.Photochemistry and photobiology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
UVB wavelengths of light induce the formation of photoproducts in genomic DNA that are potentially mutagenic and detrimental to epidermal cell function. The mineralocorticoid and androgen receptor antagonist spironolactone (SP) was recently identified as an inhibitor of UV photoproduct removal in human cancer cells in vitro via its ability to promote the rapid proteolytic degradation of the DNA repair protein XPB. Using normal human keratinocytes in vitro and skin explants ex vivo, we found that SP rapidly depleted XPB protein in both systems and abrogated two major responses to UVB-induced DNA damage, including the removal of UV photoproducts from genomic DNA and the activation of ATR/ATM DNA damage kinase signaling. These effects were also correlated with both mutagenesis and a predisposition to UVB-induced cell death but were unique to SP, because neither the SP metabolites canrenone and 7α-thiomethylspironolactone nor the more specific mineralocorticoid receptor antagonist eplerenone affected XPB protein levels or the UVB response. Our findings provide an approach for studying XPB and its roles in the UVB DNA damage response in human skin ex vivo and indicate that SP may increase UVB mutagenesis and skin cancer risk in certain individuals.
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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.