{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:52:29Z","timestamp":1790628749426,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Scientific Foundation","award":["21-15-00213"],"award-info":[{"award-number":["21-15-00213"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Ewing sarcoma (ES) is one of the most frequent types of malignant tumors among children. The active metabolic state of ES cells presents a new potential target for therapeutic interventions. As a primary regulator of cellular homeostasis, carbonic anhydrases (CAs; EC 4.2.1.1) have emerged as promising molecular targets for the development of anticancer drugs. Within the present study, we tested the commercial drug acetazolamide and our previously discovered inhibitors to target the CAII isoform, which was overexpressed and positively correlated with ES patient relapse. We employed molecular biology tests to identify effective inhibitors of CAII that can induce ferroptosis by downregulating FTH1 expression in ES cells. In vitro, we have also demonstrated their ability to reduce cell proliferation, decrease invasion, and induce apoptosis- or autophagy-related cell death. Using Western blotting, we confirmed the induction of cathepsin B in cells treated with CA inhibitors. It was found that the suppression of cathepsin B expression during the treatment reduces the anticancer efficacy of selected CAII inhibitors. These experiments highlighted profound antitumor activity of CAII inhibitors attributive to their remarkable ability to trigger ferroptosis in Ewing sarcoma cells without causing substantial host damage. The obtained results suggest that cytosolic CAII may be a prospective target for ES treatment, and CAII inhibitors can be considered as potential single-agent or combination antitumor agents to be used in the treatment of ES.<\/jats:p>","DOI":"10.3390\/cancers15215225","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T12:48:31Z","timestamp":1698756511000},"page":"5225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Carbonic Anhydrase Inhibitors Induce Ferroptosis through Inhibition of AKT\/FTH1 Signaling in Ewing Sarcoma Tumor Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Darya","family":"Fayzullina","sequence":"first","affiliation":[{"name":"Group of Experimental Biotherapy and Diagnostics, Institute for Regenerative Medicine, World-Class Research Centre \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8910-6404","authenticated-orcid":false,"given":"Semyon","family":"Yakushov","sequence":"additional","affiliation":[{"name":"Group of Experimental Biotherapy and Diagnostics, Institute for Regenerative Medicine, World-Class Research Centre \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4096-0060","authenticated-orcid":false,"given":"Kamilla","family":"Kantserova","sequence":"additional","affiliation":[{"name":"Group of Experimental Biotherapy and Diagnostics, Institute for Regenerative Medicine, World-Class Research Centre \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5853-4641","authenticated-orcid":false,"given":"Elizaveta","family":"Belyaeva","sequence":"additional","affiliation":[{"name":"Group of Experimental Biotherapy and Diagnostics, Institute for Regenerative Medicine, World-Class Research Centre \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2764-8571","authenticated-orcid":false,"given":"Denis","family":"Aniskin","sequence":"additional","affiliation":[{"name":"Group of Experimental Biotherapy and Diagnostics, Institute for Regenerative Medicine, World-Class Research Centre \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7063-205X","authenticated-orcid":false,"given":"Sergey","family":"Tsibulnikov","sequence":"additional","affiliation":[{"name":"Group of Experimental Biotherapy and Diagnostics, Institute for Regenerative Medicine, World-Class Research Centre \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nafisa","family":"Fayzullina","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6421-1208","authenticated-orcid":false,"given":"Stanislav","family":"Kalinin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Romantsova","sequence":"additional","affiliation":[{"name":"Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 115478 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Timashev","sequence":"additional","affiliation":[{"name":"World-Class Research Centre \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett A.","family":"Schroeder","sequence":"additional","affiliation":[{"name":"National Cancer Institute, Center for Cancer Research, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0818-0363","authenticated-orcid":false,"given":"Ilya V.","family":"Ulasov","sequence":"additional","affiliation":[{"name":"Group of Experimental Biotherapy and Diagnostics, Institute for Regenerative Medicine, World-Class Research Centre \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","unstructured":"Durer, S., and Shaikh, H. (2023). StatPearls, StatPearls."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.semradonc.2017.01.001","article-title":"Radiation Oncology in the Developing Economies of Central and Eastern Europe","volume":"27","author":"Esiashvili","year":"2017","journal-title":"Semin. Radiat. 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