Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures

Introduction: Introducing new drugs for clinical application is a very difficult, long, drawn-out, and costly process, which is why drug repositioning is increasingly gaining in importance. The aim of this study was to analyze the cytotoxic properties of ciprofloxacin and levofloxacin on bladder and...

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Autores principales:	Tomasz Kloskowski, Kamil Szeliski, Zuzanna Fekner, Marta Rasmus, Paweł Dąbrowski, Aleksandra Wolska, Natalia Siedlecka, Jan Adamowicz, Tomasz Drewa, Marta Pokrywczyńska
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	3D cell culture ciprofloxacin levofloxacin drug repositioning bladder cancer prostate cancer Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/a4b280ee98cc41a7b66cdd1c6ca8ae0b
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spelling	oai:doaj.org-article:a4b280ee98cc41a7b66cdd1c6ca8ae0b2021-11-11T17:23:31ZCiprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures10.3390/ijms2221119701422-00671661-6596https://doaj.org/article/a4b280ee98cc41a7b66cdd1c6ca8ae0b2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11970https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Introduction: Introducing new drugs for clinical application is a very difficult, long, drawn-out, and costly process, which is why drug repositioning is increasingly gaining in importance. The aim of this study was to analyze the cytotoxic properties of ciprofloxacin and levofloxacin on bladder and prostate cell lines in vitro. Methods: Bladder and prostate cancer cell lines together with their non-malignant counterparts were used in this study. In order to evaluate the cytotoxic effect of both drugs on tested cell lines, MTT assay, real-time cell growth analysis, apoptosis detection, cell cycle changes, molecular analysis, and 3D cultures were examined. Results: Both fluoroquinolones exhibited a toxic effect on all of the tested cell lines. In the case of non-malignant cell lines, the cytotoxic effect was weaker, which was especially pronounced in the bladder cell line. A comparison of both fluoroquinolones showed the advantage of ciprofloxacin (lower doses of drug caused a stronger cytotoxic effect). Both fluoroquinolones led to an increase in late apoptotic cells and an inhibition of cell cycle mainly in the S phase. Molecular analysis showed changes in <i>BAX</i>, <i>BCL2</i>, <i>TP53</i>, and <i>CDKN1</i> expression in tested cell lines following incubation with ciprofloxacin and levofloxacin. The downregulation of topoisomerase II genes (<i>TOP2A</i> and <i>TOP2B</i>) was noticed. Three-dimensional (3D) cell culture analysis confirmed the higher cytotoxic effect of tested fluoroquinolone against cancer cell lines. Conclusions: Our results suggest that both ciprofloxacin and levofloxacin may have great potential, especially in the supportive therapy of bladder cancer treatment. Taking into account the low costs of such therapy, fluoroquinolones seem to be ideal candidates for repositioning into bladder cancer therapeutics.Tomasz KloskowskiKamil SzeliskiZuzanna FeknerMarta RasmusPaweł DąbrowskiAleksandra WolskaNatalia SiedleckaJan AdamowiczTomasz DrewaMarta PokrywczyńskaMDPI AGarticle3D cell cultureciprofloxacinlevofloxacindrug repositioningbladder cancerprostate cancerBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11970, p 11970 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	3D cell culture ciprofloxacin levofloxacin drug repositioning bladder cancer prostate cancer Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	3D cell culture ciprofloxacin levofloxacin drug repositioning bladder cancer prostate cancer Biology (General) QH301-705.5 Chemistry QD1-999 Tomasz Kloskowski Kamil Szeliski Zuzanna Fekner Marta Rasmus Paweł Dąbrowski Aleksandra Wolska Natalia Siedlecka Jan Adamowicz Tomasz Drewa Marta Pokrywczyńska Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures
description	Introduction: Introducing new drugs for clinical application is a very difficult, long, drawn-out, and costly process, which is why drug repositioning is increasingly gaining in importance. The aim of this study was to analyze the cytotoxic properties of ciprofloxacin and levofloxacin on bladder and prostate cell lines in vitro. Methods: Bladder and prostate cancer cell lines together with their non-malignant counterparts were used in this study. In order to evaluate the cytotoxic effect of both drugs on tested cell lines, MTT assay, real-time cell growth analysis, apoptosis detection, cell cycle changes, molecular analysis, and 3D cultures were examined. Results: Both fluoroquinolones exhibited a toxic effect on all of the tested cell lines. In the case of non-malignant cell lines, the cytotoxic effect was weaker, which was especially pronounced in the bladder cell line. A comparison of both fluoroquinolones showed the advantage of ciprofloxacin (lower doses of drug caused a stronger cytotoxic effect). Both fluoroquinolones led to an increase in late apoptotic cells and an inhibition of cell cycle mainly in the S phase. Molecular analysis showed changes in <i>BAX</i>, <i>BCL2</i>, <i>TP53</i>, and <i>CDKN1</i> expression in tested cell lines following incubation with ciprofloxacin and levofloxacin. The downregulation of topoisomerase II genes (<i>TOP2A</i> and <i>TOP2B</i>) was noticed. Three-dimensional (3D) cell culture analysis confirmed the higher cytotoxic effect of tested fluoroquinolone against cancer cell lines. Conclusions: Our results suggest that both ciprofloxacin and levofloxacin may have great potential, especially in the supportive therapy of bladder cancer treatment. Taking into account the low costs of such therapy, fluoroquinolones seem to be ideal candidates for repositioning into bladder cancer therapeutics.
format	article
author	Tomasz Kloskowski Kamil Szeliski Zuzanna Fekner Marta Rasmus Paweł Dąbrowski Aleksandra Wolska Natalia Siedlecka Jan Adamowicz Tomasz Drewa Marta Pokrywczyńska
author_facet	Tomasz Kloskowski Kamil Szeliski Zuzanna Fekner Marta Rasmus Paweł Dąbrowski Aleksandra Wolska Natalia Siedlecka Jan Adamowicz Tomasz Drewa Marta Pokrywczyńska
author_sort	Tomasz Kloskowski
title	Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures
title_short	Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures
title_full	Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures
title_fullStr	Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures
title_full_unstemmed	Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures
title_sort	ciprofloxacin and levofloxacin as potential drugs in genitourinary cancer treatment—the effect of dose–response on 2d and 3d cell cultures
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a4b280ee98cc41a7b66cdd1c6ca8ae0b
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Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures

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