{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:05:16Z","timestamp":1791641116733,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T00:00:00Z","timestamp":1446508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Betulinic acid (BA), a natural compound of birch bark, is cytotoxic for many tumors. Recently, a betulinyl sulfamate was described that inhibits carbonic anhydrases (CA), such as CAIX, an attractive target for tumor-selective therapy strategies in hypoxic cancer cells. Data on combined CAIX inhibition with radiotherapy are rare. In the human breast cancer cell lines MDA-MB231 and MCF7, the effects of BA and betulinyl sulfamates on cellular and radiobiological behavior under normoxia and hypoxia were evaluated. The two most effective betulinyl sulfamates CAI 1 and CAI 3 demonstrated a 1.8\u20132.8-fold higher cytotoxicity than BA under normoxia in breast cancer cells, with IC50 values between 11.1 and 18.1 \u00b5M. BA exhibits its strongest cytotoxicity with IC50 values of 8.2 and 16.4 \u00b5M under hypoxia. All three substances show a dose-dependent increase in apoptosis, inhibition of migration, and inhibition of hypoxia-induced gene expression. In combination with irradiation, betulinyl sulfamates act as radiosensitizers, with DMF10 values of 1.47 (CAI 1) and 1.75 (CAI 3) under hypoxia in MDA-MB231 cells. BA showed additive effects in combination with irradiation. Taken together; our results suggest that BA and betulinyl sulfamates seem to be attractive substances to combine with radiotherapy; particularly for hypoxic breast cancer.<\/jats:p>","DOI":"10.3390\/ijms161125953","type":"journal-article","created":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T11:17:07Z","timestamp":1446549427000},"page":"26249-26262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Betulinyl Sulfamates as Anticancer Agents and Radiosensitizers in Human Breast Cancer Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"Matthias","family":"Bache","sequence":"first","affiliation":[{"name":"Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Stra\u00dfe 40,  D-06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christin","family":"M\u00fcnch","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Stra\u00dfe 40,  D-06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"G\u00fcttler","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Stra\u00dfe 40,  D-06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Wichmann","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Stra\u00dfe 40,  D-06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Theuerkorn","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Stra\u00dfe 40,  D-06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Emmerich","sequence":"additional","affiliation":[{"name":"Biozentrum, Martin Luther Universit\u00e4t Halle-Wittenberg, Weinbergweg 22,  D-06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Paschke","sequence":"additional","affiliation":[{"name":"Biozentrum, Martin Luther Universit\u00e4t Halle-Wittenberg, Weinbergweg 22,  D-06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Vordermark","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Stra\u00dfe 40,  D-06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.canlet.2006.11.003","article-title":"Broad in vitro efficacy of plant-derived betulinic acid against cell lines derived from the most prevalent human cancer types","volume":"251","author":"Kessler","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0304-3835(01)00718-2","article-title":"Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells","volume":"175","author":"Zuco","year":"2002","journal-title":"Cancer Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/CAD.0b013e3283421035","article-title":"Betulinic acid delivered in liposomes reduces growth of human lung and colon cancers in mice without causing systemic toxicity","volume":"22","author":"Mullauer","year":"2011","journal-title":"Anticancer Drugs"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"980","DOI":"10.2741\/3730","article-title":"Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer","volume":"16","author":"Bishayee","year":"2011","journal-title":"Front. 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