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Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.

Weiss M, Gümbel D, Hanschmann EM, Mandelkow R, Gelbrich N, Zimmermann U, Walther R, Ekkernkamp A, Sckell A, Kramer A, Burchardt M, Lillig CH, Stope MB - PLoS ONE (2015)

Bottom Line: Notably, co-administration of N-acetylcysteine (NAC) completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH).Vitamin C could not counteract the CAP induced effects on cell growth.We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.

ABSTRACT
One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP), is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS). In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC) cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC) completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH). Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

No MeSH data available.


Related in: MedlinePlus

Cold atmospheric plasma (CAP) inhibits cellular growth of human prostate cancer cells.Following CAP treatment for 10 s LNCaP and PC-3 cells were counted using a CASY Cell Counter and Analyzer Modell TT (Roche Applied Science) at indicated time points following. Control cells were treated for 10 s with argon (contr). Living cell number of (A) LNCaP cells, and (B) PC-3 cells treated with CAP revealed significantly decreased cell numbers compared to controls. (C) LNCaP cells incubated with 10 nM docetaxel showed significantly inhibited cell growth, comparable to CAP treatment. Results are expressed as the mean ± SD of cell count. *p<0.05; ***p<0.001, as determined by Student’s t test.
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pone.0130350.g002: Cold atmospheric plasma (CAP) inhibits cellular growth of human prostate cancer cells.Following CAP treatment for 10 s LNCaP and PC-3 cells were counted using a CASY Cell Counter and Analyzer Modell TT (Roche Applied Science) at indicated time points following. Control cells were treated for 10 s with argon (contr). Living cell number of (A) LNCaP cells, and (B) PC-3 cells treated with CAP revealed significantly decreased cell numbers compared to controls. (C) LNCaP cells incubated with 10 nM docetaxel showed significantly inhibited cell growth, comparable to CAP treatment. Results are expressed as the mean ± SD of cell count. *p<0.05; ***p<0.001, as determined by Student’s t test.

Mentions: In this study we aimed at analysing the short- and long-term effects of CAP on proliferation of human PC cell lines LNCaP and PC-3 after a single CAP treatment of 10 s. Argon treated cells were used as control. Using a CASY Cell Counter and Analyser Model TT the total cell number was analysed for a period of 120 h (Fig 2A and 2B). 10 s CAP application caused significant reductions in the total cell numbers of the observed cell lines LNCaP (Fig 2A; 4 h: 2.15 fold, p = 0.1138; 24 h: 1.36 fold, p = 0.2034; 48 h: 1.79 fold, p = 0.0227; 72 h: 1.88 fold, p = 0.0584; 96 h: 1.96 fold, p = 0.0148; 120 h: 2.30 fold, p = 0.0050) and PC-3 (Fig 2B; 4 h: 3.23 fold, p = 0.0040; 24 h: 1.82 fold, p = 0.0007; 48 h: 1.90 fold, p = 0.0177; 72 h: 2.01 fold, p = 0.0011; 96 h: 2.58 fold, p = 0.0010; 120 h: 2.96 fold, p = 0.0015) compared to argon-treated controls.


Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.

Weiss M, Gümbel D, Hanschmann EM, Mandelkow R, Gelbrich N, Zimmermann U, Walther R, Ekkernkamp A, Sckell A, Kramer A, Burchardt M, Lillig CH, Stope MB - PLoS ONE (2015)

Cold atmospheric plasma (CAP) inhibits cellular growth of human prostate cancer cells.Following CAP treatment for 10 s LNCaP and PC-3 cells were counted using a CASY Cell Counter and Analyzer Modell TT (Roche Applied Science) at indicated time points following. Control cells were treated for 10 s with argon (contr). Living cell number of (A) LNCaP cells, and (B) PC-3 cells treated with CAP revealed significantly decreased cell numbers compared to controls. (C) LNCaP cells incubated with 10 nM docetaxel showed significantly inhibited cell growth, comparable to CAP treatment. Results are expressed as the mean ± SD of cell count. *p<0.05; ***p<0.001, as determined by Student’s t test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488447&req=5

pone.0130350.g002: Cold atmospheric plasma (CAP) inhibits cellular growth of human prostate cancer cells.Following CAP treatment for 10 s LNCaP and PC-3 cells were counted using a CASY Cell Counter and Analyzer Modell TT (Roche Applied Science) at indicated time points following. Control cells were treated for 10 s with argon (contr). Living cell number of (A) LNCaP cells, and (B) PC-3 cells treated with CAP revealed significantly decreased cell numbers compared to controls. (C) LNCaP cells incubated with 10 nM docetaxel showed significantly inhibited cell growth, comparable to CAP treatment. Results are expressed as the mean ± SD of cell count. *p<0.05; ***p<0.001, as determined by Student’s t test.
Mentions: In this study we aimed at analysing the short- and long-term effects of CAP on proliferation of human PC cell lines LNCaP and PC-3 after a single CAP treatment of 10 s. Argon treated cells were used as control. Using a CASY Cell Counter and Analyser Model TT the total cell number was analysed for a period of 120 h (Fig 2A and 2B). 10 s CAP application caused significant reductions in the total cell numbers of the observed cell lines LNCaP (Fig 2A; 4 h: 2.15 fold, p = 0.1138; 24 h: 1.36 fold, p = 0.2034; 48 h: 1.79 fold, p = 0.0227; 72 h: 1.88 fold, p = 0.0584; 96 h: 1.96 fold, p = 0.0148; 120 h: 2.30 fold, p = 0.0050) and PC-3 (Fig 2B; 4 h: 3.23 fold, p = 0.0040; 24 h: 1.82 fold, p = 0.0007; 48 h: 1.90 fold, p = 0.0177; 72 h: 2.01 fold, p = 0.0011; 96 h: 2.58 fold, p = 0.0010; 120 h: 2.96 fold, p = 0.0015) compared to argon-treated controls.

Bottom Line: Notably, co-administration of N-acetylcysteine (NAC) completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH).Vitamin C could not counteract the CAP induced effects on cell growth.We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.

ABSTRACT
One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP), is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS). In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC) cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC) completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH). Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

No MeSH data available.


Related in: MedlinePlus