Non-thermal plasma as promising anti-cancer therapy against bladder cancer by inducing DNA damage and cell cycle arrest

Abstract Bladder cancer often recurs, necessitating innovative treatments to reduce recurrence. We investigated non-thermal plasma’s potential as a novel anti-cancer therapy, focusing on plasma-activated solution (PAS), created by exposing saline to non-thermal plasma. Our study aims to elucidate th...

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Main Authors: Jojanneke Stoof, Zakaria Kalmoua, Ana Sobota, Ruud H. Brakenhoff, Marijke Stigter, Thang V. Pham, Sander R. Piersma, Alex Henneman, Tonny Lagerweij, Richard de Goeij-de Haas, R. Jeroen A. van Moorselaar, Connie R. Jimenez, Irene V. Bijnsdorp
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-85568-0
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author Jojanneke Stoof
Zakaria Kalmoua
Ana Sobota
Ruud H. Brakenhoff
Marijke Stigter
Thang V. Pham
Sander R. Piersma
Alex Henneman
Tonny Lagerweij
Richard de Goeij-de Haas
R. Jeroen A. van Moorselaar
Connie R. Jimenez
Irene V. Bijnsdorp
author_facet Jojanneke Stoof
Zakaria Kalmoua
Ana Sobota
Ruud H. Brakenhoff
Marijke Stigter
Thang V. Pham
Sander R. Piersma
Alex Henneman
Tonny Lagerweij
Richard de Goeij-de Haas
R. Jeroen A. van Moorselaar
Connie R. Jimenez
Irene V. Bijnsdorp
author_sort Jojanneke Stoof
collection DOAJ
description Abstract Bladder cancer often recurs, necessitating innovative treatments to reduce recurrence. We investigated non-thermal plasma’s potential as a novel anti-cancer therapy, focusing on plasma-activated solution (PAS), created by exposing saline to non-thermal plasma. Our study aims to elucidate the biological effects of PAS on bladder cancer cell lines in vitro, as well as the combination with mitomycin C (MMC), using clinically relevant settings. PAS treatment exerts a potent cytotoxic effect through the production of intracellular reactive oxygen species, resulting in DNA damage and subsequent induction of G1 cell cycle arrest/senescence. This is induced via upregulation of cell cycle checkpoint signalling and DNA damage repair pathways using LC-M/MS-based phospho-proteomics. Importantly, combining PAS with MMC reveals a synergistic effect (Combination Index of 0.59–0.67), suggesting the potential of utilizing PAS in combination therapies. Our findings demonstrate PAS’s mode of action and suggest its potential as a promising treatment for bladder cancer, warranting further clinical studies.
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spelling doaj-art-e2b877d8a49345e78dd1b908153d5aa82025-01-19T12:19:18ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-025-85568-0Non-thermal plasma as promising anti-cancer therapy against bladder cancer by inducing DNA damage and cell cycle arrestJojanneke Stoof0Zakaria Kalmoua1Ana Sobota2Ruud H. Brakenhoff3Marijke Stigter4Thang V. Pham5Sander R. Piersma6Alex Henneman7Tonny Lagerweij8Richard de Goeij-de Haas9R. Jeroen A. van Moorselaar10Connie R. Jimenez11Irene V. Bijnsdorp12Amsterdam UMC, Location VUmc, Cancer Center AmsterdamAmsterdam UMC, Location VUmc, Cancer Center AmsterdamDepartment of Applied Physics and Science Education, Eindhoven University of TechnologyAmsterdam UMC, Location VUmc, Cancer Center AmsterdamAmsterdam UMC, Location VUmc, Cancer Center AmsterdamAmsterdam UMC, Location VUmc, Cancer Center AmsterdamAmsterdam UMC, Location VUmc, Cancer Center AmsterdamAmsterdam UMC, Location VUmc, Cancer Center AmsterdamAmsterdam UMC, Location VUmc, Cancer Center AmsterdamAmsterdam UMC, Location VUmc, Cancer Center AmsterdamAmsterdam UMC, Location VUmc, Cancer Center AmsterdamAmsterdam UMC, Location VUmc, Cancer Center AmsterdamAmsterdam UMC, Location VUmc, Cancer Center AmsterdamAbstract Bladder cancer often recurs, necessitating innovative treatments to reduce recurrence. We investigated non-thermal plasma’s potential as a novel anti-cancer therapy, focusing on plasma-activated solution (PAS), created by exposing saline to non-thermal plasma. Our study aims to elucidate the biological effects of PAS on bladder cancer cell lines in vitro, as well as the combination with mitomycin C (MMC), using clinically relevant settings. PAS treatment exerts a potent cytotoxic effect through the production of intracellular reactive oxygen species, resulting in DNA damage and subsequent induction of G1 cell cycle arrest/senescence. This is induced via upregulation of cell cycle checkpoint signalling and DNA damage repair pathways using LC-M/MS-based phospho-proteomics. Importantly, combining PAS with MMC reveals a synergistic effect (Combination Index of 0.59–0.67), suggesting the potential of utilizing PAS in combination therapies. Our findings demonstrate PAS’s mode of action and suggest its potential as a promising treatment for bladder cancer, warranting further clinical studies.https://doi.org/10.1038/s41598-025-85568-0Non-thermal plasmaPhospho-proteomicsBladder cancerCancer therapyPlasma oncology
spellingShingle Jojanneke Stoof
Zakaria Kalmoua
Ana Sobota
Ruud H. Brakenhoff
Marijke Stigter
Thang V. Pham
Sander R. Piersma
Alex Henneman
Tonny Lagerweij
Richard de Goeij-de Haas
R. Jeroen A. van Moorselaar
Connie R. Jimenez
Irene V. Bijnsdorp
Non-thermal plasma as promising anti-cancer therapy against bladder cancer by inducing DNA damage and cell cycle arrest
Scientific Reports
Non-thermal plasma
Phospho-proteomics
Bladder cancer
Cancer therapy
Plasma oncology
title Non-thermal plasma as promising anti-cancer therapy against bladder cancer by inducing DNA damage and cell cycle arrest
title_full Non-thermal plasma as promising anti-cancer therapy against bladder cancer by inducing DNA damage and cell cycle arrest
title_fullStr Non-thermal plasma as promising anti-cancer therapy against bladder cancer by inducing DNA damage and cell cycle arrest
title_full_unstemmed Non-thermal plasma as promising anti-cancer therapy against bladder cancer by inducing DNA damage and cell cycle arrest
title_short Non-thermal plasma as promising anti-cancer therapy against bladder cancer by inducing DNA damage and cell cycle arrest
title_sort non thermal plasma as promising anti cancer therapy against bladder cancer by inducing dna damage and cell cycle arrest
topic Non-thermal plasma
Phospho-proteomics
Bladder cancer
Cancer therapy
Plasma oncology
url https://doi.org/10.1038/s41598-025-85568-0
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