Newly developed dual topoisomerase inhibitor P8-D6 is highly active in ovarian cancer

Background: Ovarian cancer (OvCa) constitutes a rare and highly aggressive malignancy and is one of the most lethal of all gynaecologic neoplasms. Due to chemotherapy resistance and treatment limitations because of side effects, OvCa is still not sufficiently treatable. Hence, new drugs for OvCa the...

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Autores principales:	Inken Flörkemeier, Tamara N. Steinhauer, Nina Hedemann, Magnus Ölander, Per Artursson, Bernd Clement, Dirk O. Bauerschlag
Formato:	article
Lenguaje:	EN
Publicado:	SAGE Publishing 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/8b89334405764c299bc1e0e335c0f7dc
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spelling	oai:doaj.org-article:8b89334405764c299bc1e0e335c0f7dc2021-12-01T23:33:30ZNewly developed dual topoisomerase inhibitor P8-D6 is highly active in ovarian cancer1758-835910.1177/17588359211059896https://doaj.org/article/8b89334405764c299bc1e0e335c0f7dc2021-11-01T00:00:00Zhttps://doi.org/10.1177/17588359211059896https://doaj.org/toc/1758-8359Background: Ovarian cancer (OvCa) constitutes a rare and highly aggressive malignancy and is one of the most lethal of all gynaecologic neoplasms. Due to chemotherapy resistance and treatment limitations because of side effects, OvCa is still not sufficiently treatable. Hence, new drugs for OvCa therapy such as P8-D6 with promising antitumour properties have a high clinical need. The benzo[ c ]phenanthridine P8-D6 is an effective inductor of apoptosis by acting as a dual topoisomerase I/II inhibitor. Methods: In the present study, the effectiveness of P8-D6 on OvCa was investigated in vitro . In various OvCa cell lines and ex vivo primary cells, the apoptosis induction compared with standard therapeutic agents was determined in two-dimensional monolayers. Expanded by three-dimensional and co-culture, the P8-D6 treated cells were examined for changes in cytotoxicity, apoptosis rate and membrane integrity via scanning electron microscopy (SEM). Likewise, the effects of P8-D6 on non-cancer human ovarian surface epithelial cells and primary human hepatocytes were determined. Results: This study shows a significant P8-D6-induced increase in apoptosis and cytotoxicity in OvCa cells which surpasses the efficacy of well-established drugs like cisplatin or the topoisomerase inhibitors etoposide and topotecan. Non-cancer cells were affected only slightly by P8-D6. Moreover, no hepatotoxic effect in in vitro studies was detected. Conclusion: P8-D6 is a strong and rapid inductor of apoptosis and might be a novel treatment option for OvCa therapy.Inken FlörkemeierTamara N. SteinhauerNina HedemannMagnus ÖlanderPer ArturssonBernd ClementDirk O. BauerschlagSAGE PublishingarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENTherapeutic Advances in Medical Oncology, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Inken Flörkemeier Tamara N. Steinhauer Nina Hedemann Magnus Ölander Per Artursson Bernd Clement Dirk O. Bauerschlag Newly developed dual topoisomerase inhibitor P8-D6 is highly active in ovarian cancer
description	Background: Ovarian cancer (OvCa) constitutes a rare and highly aggressive malignancy and is one of the most lethal of all gynaecologic neoplasms. Due to chemotherapy resistance and treatment limitations because of side effects, OvCa is still not sufficiently treatable. Hence, new drugs for OvCa therapy such as P8-D6 with promising antitumour properties have a high clinical need. The benzo[ c ]phenanthridine P8-D6 is an effective inductor of apoptosis by acting as a dual topoisomerase I/II inhibitor. Methods: In the present study, the effectiveness of P8-D6 on OvCa was investigated in vitro . In various OvCa cell lines and ex vivo primary cells, the apoptosis induction compared with standard therapeutic agents was determined in two-dimensional monolayers. Expanded by three-dimensional and co-culture, the P8-D6 treated cells were examined for changes in cytotoxicity, apoptosis rate and membrane integrity via scanning electron microscopy (SEM). Likewise, the effects of P8-D6 on non-cancer human ovarian surface epithelial cells and primary human hepatocytes were determined. Results: This study shows a significant P8-D6-induced increase in apoptosis and cytotoxicity in OvCa cells which surpasses the efficacy of well-established drugs like cisplatin or the topoisomerase inhibitors etoposide and topotecan. Non-cancer cells were affected only slightly by P8-D6. Moreover, no hepatotoxic effect in in vitro studies was detected. Conclusion: P8-D6 is a strong and rapid inductor of apoptosis and might be a novel treatment option for OvCa therapy.
format	article
author	Inken Flörkemeier Tamara N. Steinhauer Nina Hedemann Magnus Ölander Per Artursson Bernd Clement Dirk O. Bauerschlag
author_facet	Inken Flörkemeier Tamara N. Steinhauer Nina Hedemann Magnus Ölander Per Artursson Bernd Clement Dirk O. Bauerschlag
author_sort	Inken Flörkemeier
title	Newly developed dual topoisomerase inhibitor P8-D6 is highly active in ovarian cancer
title_short	Newly developed dual topoisomerase inhibitor P8-D6 is highly active in ovarian cancer
title_full	Newly developed dual topoisomerase inhibitor P8-D6 is highly active in ovarian cancer
title_fullStr	Newly developed dual topoisomerase inhibitor P8-D6 is highly active in ovarian cancer
title_full_unstemmed	Newly developed dual topoisomerase inhibitor P8-D6 is highly active in ovarian cancer
title_sort	newly developed dual topoisomerase inhibitor p8-d6 is highly active in ovarian cancer
publisher	SAGE Publishing
publishDate	2021
url	https://doaj.org/article/8b89334405764c299bc1e0e335c0f7dc
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Newly developed dual topoisomerase inhibitor P8-D6 is highly active in ovarian cancer

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