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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

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: Kloskowski, Tomasz, Szeliski, Kamil, Fekner, Zuzanna, Rasmus, Marta, Dąbrowski, Paweł, Wolska, Aleksandra, Siedlecka, Natalia, Adamowicz, Jan, Drewa, Tomasz, Pokrywczyńska, Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584631/
https://www.ncbi.nlm.nih.gov/pubmed/34769400
http://dx.doi.org/10.3390/ijms222111970
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author Kloskowski, Tomasz
Szeliski, Kamil
Fekner, Zuzanna
Rasmus, Marta
Dąbrowski, Paweł
Wolska, Aleksandra
Siedlecka, Natalia
Adamowicz, Jan
Drewa, Tomasz
Pokrywczyńska, Marta
author_facet Kloskowski, Tomasz
Szeliski, Kamil
Fekner, Zuzanna
Rasmus, Marta
Dąbrowski, Paweł
Wolska, Aleksandra
Siedlecka, Natalia
Adamowicz, Jan
Drewa, Tomasz
Pokrywczyńska, Marta
author_sort Kloskowski, Tomasz
collection PubMed
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 BAX, BCL2, TP53, and CDKN1 expression in tested cell lines following incubation with ciprofloxacin and levofloxacin. The downregulation of topoisomerase II genes (TOP2A and TOP2B) 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.
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spelling pubmed-85846312021-11-12 Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures Kloskowski, Tomasz Szeliski, Kamil Fekner, Zuzanna Rasmus, Marta Dąbrowski, Paweł Wolska, Aleksandra Siedlecka, Natalia Adamowicz, Jan Drewa, Tomasz Pokrywczyńska, Marta Int J Mol Sci Article 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 BAX, BCL2, TP53, and CDKN1 expression in tested cell lines following incubation with ciprofloxacin and levofloxacin. The downregulation of topoisomerase II genes (TOP2A and TOP2B) 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. MDPI 2021-11-04 /pmc/articles/PMC8584631/ /pubmed/34769400 http://dx.doi.org/10.3390/ijms222111970 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kloskowski, Tomasz
Szeliski, Kamil
Fekner, Zuzanna
Rasmus, Marta
Dąbrowski, Paweł
Wolska, Aleksandra
Siedlecka, Natalia
Adamowicz, Jan
Drewa, Tomasz
Pokrywczyńska, Marta
Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584631/
https://www.ncbi.nlm.nih.gov/pubmed/34769400
http://dx.doi.org/10.3390/ijms222111970
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