{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T11:10:27Z","timestamp":1781521827524,"version":"3.54.1"},"reference-count":94,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Faculty of Kiel University","award":["BMBF 03VP08790"],"award-info":[{"award-number":["BMBF 03VP08790"]}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["BMBF 03VP08790"],"award-info":[{"award-number":["BMBF 03VP08790"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DampStiftung","award":["BMBF 03VP08790"],"award-info":[{"award-number":["BMBF 03VP08790"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite advances in vaccination and early detection, the total number of cases and deaths from cervical cancer has risen steadily in recent decades, making it the fourth most common type of cancer in women worldwide. Low-income countries in particular struggle with limited resources and treatment limitations for cervical cancer. Thus, effective medicines that are simple to manufacture are needed. The newly developed dual topoisomerase inhibitor P8-D6, with its outstanding ability to induce apoptosis, could be a promising option. In this study, the efficacy of P8-D6 in combination with radiochemotherapy against cervical carcinoma was investigated in established cell lines and in a translational approach in ex vivo patient cells by measuring the cytotoxicity, cell viability and caspase activity in vitro in 2D and 3D cell cultures. Treatment with P8-D6 resulted in significantly greater cytotoxicity and apoptosis induction compared to standard therapeutic cisplatin in both 2D and 3D cell cultures. Specifically, a considerably stronger anti-proliferative effect was observed. The treatment also led to morphological changes and a loss of membrane integrity in the 3D spheroids. Radiotherapy also benefited greatly from P8-D6 treatment. In fact, P8-D6 was a more potent radiosensitizer than cisplatin. Simple synthesis, favorable physicochemical properties and high potency make P8-D6 a promising cervical cancer drug candidate.<\/jats:p>","DOI":"10.3390\/ijms26072829","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T04:58:38Z","timestamp":1742533118000},"page":"2829","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dual Topoisomerase Inhibitor Is Highly Potent and Improves Antitumor Response to Radiotherapy in Cervical Carcinoma"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5885-6352","authenticated-orcid":false,"given":"Inken","family":"Fl\u00f6rkemeier","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"},{"name":"Pharmaceutical Institute, Department of Pharmaceutical and Medicinal Chemistry, Christian-Albrecht University of Kiel, 24118 Kiel, Germany"},{"name":"Priority Research Area Kiel Nano, Surface and Interface Sciences (KiNSIS), Kiel University, 24118 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah L.","family":"Hotze","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Lena","family":"Heyne","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"},{"name":"Pharmaceutical Institute, Department of Pharmaceutical and Medicinal Chemistry, Christian-Albrecht University of Kiel, 24118 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Pharmaceutical Institute, Department of Pharmaceutical and Medicinal Chemistry, Christian-Albrecht University of Kiel, 24118 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4528-8509","authenticated-orcid":false,"given":"J\u00f6rg P.","family":"Weimer","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Hedemann","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Rogmans","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7012-5605","authenticated-orcid":false,"given":"David","family":"Holthaus","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank-Andr\u00e9","family":"Siebert","sequence":"additional","affiliation":[{"name":"Clinic of Radiotherapy, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hirt","sequence":"additional","affiliation":[{"name":"Clinic of Radiotherapy, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Polten","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Morgan","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00fcdiger","family":"Klapdor","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Department of Gynecology and Obstetrics, Albertinen Hospital Hamburg, 22457 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Schambach","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Division of Hematology\/Oncology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2618-3920","authenticated-orcid":false,"given":"Astrid","family":"Dempfle","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics and Statistics, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Maass","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion T.","family":"van Mackelenbergh","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Clement","sequence":"additional","affiliation":[{"name":"Pharmaceutical Institute, Department of Pharmaceutical and Medicinal Chemistry, Christian-Albrecht University of Kiel, 24118 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk O.","family":"Bauerschlag","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"},{"name":"Department of Gynecology, Jena University Hospital, 07747 Jena, 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