Effect of four fluoroquinolones on the viability of bladder cancer cells in 2D and 3D cultures

IntroductionThe anticancer properties of fluoroquinolones and the high concentrations they achieve in urine may help in bladder cancer therapy. This study aimed to analyze the properties of 4 fluoroquinolones as potential candidates for supportive treatment of bladder cancer. MethodsComparative anal...

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Main Authors: Tomasz Kloskowski, Zuzanna Fekner, Kamil Szeliski, Michelle Paradowska, Daria Balcerczyk, Marta Rasmus, Paweł Dąbrowski, Łukasz Kaźmierski, Tomasz Drewa, Marta Pokrywczyńska
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2023.1222411/full
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author Tomasz Kloskowski
Zuzanna Fekner
Kamil Szeliski
Michelle Paradowska
Daria Balcerczyk
Marta Rasmus
Paweł Dąbrowski
Łukasz Kaźmierski
Tomasz Drewa
Tomasz Drewa
Marta Pokrywczyńska
author_facet Tomasz Kloskowski
Zuzanna Fekner
Kamil Szeliski
Michelle Paradowska
Daria Balcerczyk
Marta Rasmus
Paweł Dąbrowski
Łukasz Kaźmierski
Tomasz Drewa
Tomasz Drewa
Marta Pokrywczyńska
author_sort Tomasz Kloskowski
collection DOAJ
description IntroductionThe anticancer properties of fluoroquinolones and the high concentrations they achieve in urine may help in bladder cancer therapy. This study aimed to analyze the properties of 4 fluoroquinolones as potential candidates for supportive treatment of bladder cancer. MethodsComparative analyses were performed on the cytotoxic effects of norfloxacin, enrofloxacin, moxifloxacin, and ofloxacin on normal and cancer urothelial cell lines. In 2D culture, the cytotoxic properties of fluoroquinolones were evaluated using MTT assay, real-time cell growth analysis, fluorescence and light microscopy, flow cytometry, and molecular analysis. In 3D culture, the properties of fluoroquinolones were tested using luminescence assays and confocal microscopy.Results and DiscussionAll tested fluoroquinolones in 2D culture decreased the viability of both tested cell lines in a dose- and timedependent manner. Lower concentrations did not influence cell morphology and cytoskeletal organization. In higher concentrations, destruction of the actin cytoskeleton and shrinkage of the nucleus was visible. Flow cytometry analysis showed cell cycle inhibition of bladder cancer cell lines in the G2/M phase. This influence was minimal in the case of normal urothelium cells. In both tested cell lines, increases in the number of late apoptotic cells were observed. Molecular analysis showed variable expression of studied genes depending on the drug and concentration. In 3D culture, tested drugs were effective only in the highest tested concentrations which was accompanied by caspase 3/7 activation and cytoskeleton degradation. This effect was hardly visible in non-cancer cell lines. According to the data, norfloxacin and enrofloxacin had the most promising properties. These two fluoroquinolones exhibited the highest cytotoxic properties against both tested cell lines. In the case of norfloxacin, almost all calculated LC values for bladder cancer cell lines were achievable in the urine. Enrofloxacin and norfloxacin can be used to support chemotherapy in bladder cancer patients.
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spelling doaj.art-db50ea51cd1346cb96b170d00d7920fd2023-07-18T08:14:14ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-07-011310.3389/fonc.2023.12224111222411Effect of four fluoroquinolones on the viability of bladder cancer cells in 2D and 3D culturesTomasz Kloskowski0Zuzanna Fekner1Kamil Szeliski2Michelle Paradowska3Daria Balcerczyk4Marta Rasmus5Paweł Dąbrowski6Łukasz Kaźmierski7Tomasz Drewa8Tomasz Drewa9Marta Pokrywczyńska10Chair of Urology and Andrology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandChair of Urology and Andrology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandChair of Urology and Andrology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandChair of Urology and Andrology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandChair of Urology and Andrology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandChair of Urology and Andrology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandChair of Urology and Andrology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandChair of Urology and Andrology, Department of Tissue Engineering, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandChair of Urology and Andrology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandChair of Urology and Andrology, Department of Tissue Engineering, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandChair of Urology and Andrology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandIntroductionThe anticancer properties of fluoroquinolones and the high concentrations they achieve in urine may help in bladder cancer therapy. This study aimed to analyze the properties of 4 fluoroquinolones as potential candidates for supportive treatment of bladder cancer. MethodsComparative analyses were performed on the cytotoxic effects of norfloxacin, enrofloxacin, moxifloxacin, and ofloxacin on normal and cancer urothelial cell lines. In 2D culture, the cytotoxic properties of fluoroquinolones were evaluated using MTT assay, real-time cell growth analysis, fluorescence and light microscopy, flow cytometry, and molecular analysis. In 3D culture, the properties of fluoroquinolones were tested using luminescence assays and confocal microscopy.Results and DiscussionAll tested fluoroquinolones in 2D culture decreased the viability of both tested cell lines in a dose- and timedependent manner. Lower concentrations did not influence cell morphology and cytoskeletal organization. In higher concentrations, destruction of the actin cytoskeleton and shrinkage of the nucleus was visible. Flow cytometry analysis showed cell cycle inhibition of bladder cancer cell lines in the G2/M phase. This influence was minimal in the case of normal urothelium cells. In both tested cell lines, increases in the number of late apoptotic cells were observed. Molecular analysis showed variable expression of studied genes depending on the drug and concentration. In 3D culture, tested drugs were effective only in the highest tested concentrations which was accompanied by caspase 3/7 activation and cytoskeleton degradation. This effect was hardly visible in non-cancer cell lines. According to the data, norfloxacin and enrofloxacin had the most promising properties. These two fluoroquinolones exhibited the highest cytotoxic properties against both tested cell lines. In the case of norfloxacin, almost all calculated LC values for bladder cancer cell lines were achievable in the urine. Enrofloxacin and norfloxacin can be used to support chemotherapy in bladder cancer patients.https://www.frontiersin.org/articles/10.3389/fonc.2023.1222411/fullbladder cancerfluoroquinolonesenrofloxacin (ENR)moxifloxacin (MOX)ofloxacin (OFL)norfloxacin (NFX)
spellingShingle Tomasz Kloskowski
Zuzanna Fekner
Kamil Szeliski
Michelle Paradowska
Daria Balcerczyk
Marta Rasmus
Paweł Dąbrowski
Łukasz Kaźmierski
Tomasz Drewa
Tomasz Drewa
Marta Pokrywczyńska
Effect of four fluoroquinolones on the viability of bladder cancer cells in 2D and 3D cultures
Frontiers in Oncology
bladder cancer
fluoroquinolones
enrofloxacin (ENR)
moxifloxacin (MOX)
ofloxacin (OFL)
norfloxacin (NFX)
title Effect of four fluoroquinolones on the viability of bladder cancer cells in 2D and 3D cultures
title_full Effect of four fluoroquinolones on the viability of bladder cancer cells in 2D and 3D cultures
title_fullStr Effect of four fluoroquinolones on the viability of bladder cancer cells in 2D and 3D cultures
title_full_unstemmed Effect of four fluoroquinolones on the viability of bladder cancer cells in 2D and 3D cultures
title_short Effect of four fluoroquinolones on the viability of bladder cancer cells in 2D and 3D cultures
title_sort effect of four fluoroquinolones on the viability of bladder cancer cells in 2d and 3d cultures
topic bladder cancer
fluoroquinolones
enrofloxacin (ENR)
moxifloxacin (MOX)
ofloxacin (OFL)
norfloxacin (NFX)
url https://www.frontiersin.org/articles/10.3389/fonc.2023.1222411/full
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