Non-thermal plasma as promising anti-cancer therapy against bladder cancer by inducing DNA damage and cell cycle
Jojanneke Stoof1,2,3,4, Zakaria Kalmoua1,2,3,4, Ana Sobota5
1Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, de Boelelaan 1117, 1018 HV, Amsterdam, The Netherlands.
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.
Insights
Plasma-activated solution (PAS) shows promise for treating bladder cancer by damaging cancer cells and synergizing with chemotherapy. Further clinical studies are warranted for this innovative therapy.
Area of Science:
- Biomedical Engineering
- Oncology
- Plasma Physics
Background:
- Bladder cancer frequently recurs, driving the need for novel therapeutic strategies.
- Non-thermal plasma is an emerging technology with potential anti-cancer applications.
- Plasma-activated solution (PAS) is generated by treating saline with non-thermal plasma.
Purpose of the Study:
- To investigate the anti-cancer effects of PAS on bladder cancer cell lines in vitro.
- To explore the combined efficacy of PAS with mitomycin C (MMC).
- To elucidate the underlying mechanisms of PAS-induced cytotoxicity.
Main Methods:
- Exposure of bladder cancer cell lines to PAS.
- Combination treatment with PAS and mitomycin C (MMC).
- Analysis of cellular effects using LC-MS/MS-based phospho-proteomics to study cell cycle and DNA damage pathways.
Main Results:
- PAS demonstrated significant cytotoxic effects on bladder cancer cells.
- PAS induced intracellular reactive oxygen species, DNA damage, and G1 cell cycle arrest/senescence.
- A synergistic effect was observed when PAS was combined with MMC (Combination Index: 0.59-0.67).
Conclusions:
- PAS exhibits a potent anti-cancer mechanism involving oxidative stress and DNA damage.
- PAS holds potential as a novel therapeutic agent for bladder cancer.
- The synergistic interaction between PAS and MMC suggests its utility in combination therapies, meriting further clinical investigation.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...