ArticleThe Journal of investigative dermatology2015
Omeprazole, a gastric proton pump inhibitor, inhibits melanogenesis by blocking ATP7A trafficking.
Article in The Journal of investigative dermatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Ferroptosis and Cuproptosis in Cancer and Neurodegeneration: A Comprehensive Review of Modulation by Iron and Copper Chelators and Related Agents.Biomolecules · 2026Review
- Robustness Analyses Substantially Narrow in silico Network-Toxicology Signals Linking Selected Pharmaceuticals and Caffeine to Vitiligo.Clinical, cosmetic and investigational dermatology · 2026Article
- Article
- Melasma Management: A Comprehensive Review of Treatment Strategies Including BTX-A.Journal of cosmetic dermatology · 2025Review
- Reprogramming the melanoma and immunosuppressive myeloid cells with esomeprazole-loaded PLGA nanoparticles.iScience · 2025Article
- Update on Melasma Treatments.Annals of dermatology · 2024Review
- Novel insights into cuproptosis inducers and inhibitors.Frontiers in molecular biosciences · 2024Review
- Repurposing of rabeprazole as an anti-Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Understanding Melasma-How Can Pharmacology and Cosmetology Procedures and Prevention Help to Achieve Optimal Treatment Results? A Narrative Review.International journal of environmental research and public health · 2022Review
- Quantitative Ubiquitinomics Revealed Abnormal Ubiquitinated ATP7A Involved in Down-Regulation of ACTH in Silent Corticotroph Adenomas.Frontiers in endocrinology · 2022Article
- Vitiligo, alkaptonuria, and nitisinone-A report of three families and review of the literature.JIMD reports · 2021Article
- Membrane Transporters and Channels in Melanoma.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer.Nature communications · 2020Article
- Copper chaperone ATOX1 is required for MAPK signaling and growth in BRAF mutation-positive melanoma.Metallomics : integrated biometal science · 2019Article
- Active repurposing of drug candidates for melanoma based on GWAS, PheWAS and a wide range of omics data.Molecular medicine (Cambridge, Mass.) · 2019Article
- Targeting acidity in cancer and diabetes.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Developing drugs targeting transition metal homeostasis.Current opinion in chemical biology · 2017Review
- Proton pump inhibitors decrease eotaxin-3/CCL26 expression in patients with chronic rhinosinusitis with nasal polyps: Possible role of the nongastric H,K-ATPase.The Journal of allergy and clinical immunology · 2017Article
- A Role for The ATP7A Copper Transporter in Tumorigenesis and Cisplatin Resistance.Journal of Cancer · 2017Article
- Cancer: fundamentals behind pH targeting and the double-edged approach.OncoTargets and therapy · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Omeprazole is a proton pump inhibitor used in the treatment of peptic ulcer disease and gastrosophageal reflux disease and acts by irreversibly blocking ATP4A, a P-type H+/K+ ATPase in gastric parietal cells. We found that omeprazole and its closely related congeners inhibited melanogenesis at micromolar concentrations in B16 mouse melanoma cells, normal human epidermal melanocytes, and in a reconstructed human skin model. Omeprazole topically applied to the skin of UV-irradiated human subjects significantly reduced pigment levels after 3 weeks compared with untreated controls. Omeprazole had no significant inhibitory effect on the activities of purified human tyrosinase or on the mRNA levels of tyrosinase, dopachrome tautomerase, Pmel17, or MITF mRNA levels. Although melanocytes do not express ATP4A, they do express ATP7A, a copper transporting P-type ATPase in the trans-Golgi network that is required for copper acquisition by tyrosinase. ATP7A relocalization from the trans-Golgi network to the plasma membrane in response to elevated copper concentrations in melanocytes was inhibited by omeprazole. Omeprazole treatment increased the proportion of EndoH sensitive tyrosinase, indicating that tyrosinase maturation was impaired. In addition, omeprazole reduced tyrosinase protein abundance in the presence of cycloheximide, suggestive of increased degradation. Our findings are consistent with the hypothesis that omeprazole reduces melanogenesis by inhibiting ATP7A and by enhancing degradation of tyrosinase.
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