{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:29:07Z","timestamp":1792250947968,"version":"4.4.0"},"reference-count":71,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T00:00:00Z","timestamp":1607472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brigitta and Norbert Muth Foundation","award":["2018_BCa"],"award-info":[{"award-number":["2018_BCa"]}]},{"name":"Hilfe f\u00fcr krebskranke Kinder Frankfurt e.V.","award":["2016"],"award-info":[{"award-number":["2016"]}]},{"name":"Frankfurter Stiftung f\u00fcr krebskranke Kinder","award":["2016"],"award-info":[{"award-number":["2016"]}]},{"name":"Kent Cancer Trust","award":["2016"],"award-info":[{"award-number":["2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cisplatin, which induces DNA damage, is standard chemotherapy for advanced bladder cancer (BCa). However, efficacy is limited due to resistance development. Since artesunate (ART), a derivative of artemisinin originating from Traditional Chinese Medicine, has been shown to exhibit anti-tumor activity, and to inhibit DNA damage repair, the impact of artesunate on cisplatin-resistant BCa was evaluated. Cisplatin-sensitive (parental) and cisplatin-resistant BCa cells, RT4, RT112, T24, and TCCSup, were treated with ART (1\u2013100 \u00b5M). Cell growth, proliferation, and cell cycle phases were investigated, as were apoptosis, necrosis, ferroptosis, autophagy, metabolic activity, and protein expression. Exposure to ART induced a time- and dose-dependent significant inhibition of tumor cell growth and proliferation of parental and cisplatin-resistant BCa cells. This inhibition was accompanied by a G0\/G1 phase arrest and modulation of cell cycle regulating proteins. ART induced apoptos is by enhancing DNA damage, especially in the resistant cells. ART did not induce ferroptosis, but led to a disturbance of mitochondrial respiration and ATP generation. This impairment correlated with autophagy accompanied by a decrease in LC3B-I and an increase in LC3B-II. Since ART significantly inhibits proliferative and metabolic aspects of cisplatin-sensitive and cisplatin-resistant BCa cells, it may hold potential in treating advanced and therapy-resistant BCa.<\/jats:p>","DOI":"10.3390\/cells9122643","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T20:18:22Z","timestamp":1607631502000},"page":"2643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":108,"title":["Artesunate Impairs Growth in Cisplatin-Resistant Bladder Cancer Cells by Cell Cycle Arrest, Apoptosis and Autophagy Induction"],"prefix":"10.3390","volume":"9","author":[{"given":"Fuguang","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olesya","family":"Vakhrusheva","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha D.","family":"Markowitsch","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly S.","family":"Slade","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5107-3523","authenticated-orcid":false,"given":"Igor","family":"Tsaur","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Jindrich","family":"Cinatl","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, Goethe-University, 60596 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5710-5888","authenticated-orcid":false,"given":"Martin","family":"Michaelis","sequence":"additional","affiliation":[{"name":"Industrial Biotechnology Centre, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3266-4050","authenticated-orcid":false,"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Haferkamp","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Juengel","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1007\/s00120-016-0195-1","article-title":"[Short version of the German S3 guideline for bladder cancer]","volume":"55","author":"Retz","year":"2016","journal-title":"Urologe A"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Witjes, J.A., Bruins, H.M., Cathomas, R., Comperat, E.M., Cowan, N.C., Gakis, G., Hernandez, V., Linares Espinos, E., Lorch, A., and Neuzillet, Y. 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