Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways
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{"title"=>"Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways", "type"=>"journal", "authors"=>[{"first_name"=>"Martin", "last_name"=>"Weiss"}, {"first_name"=>"Denis", "last_name"=>"Gümbel"}, {"first_name"=>"Eva-Maria", "last_name"=>"Hanschmann"}, {"first_name"=>"Robert", "last_name"=>"Mandelkow"}, {"first_name"=>"Nadine", "last_name"=>"Gelbrich"}, {"first_name"=>"Uwe", "last_name"=>"Zimmermann"}, {"first_name"=>"Reinhard", "last_name"=>"Walther"}, {"first_name"=>"Axel", "last_name"=>"Ekkernkamp"}, {"first_name"=>"Axel", "last_name"=>"Sckell"}, {"first_name"=>"Axel", "last_name"=>"Kramer"}, {"first_name"=>"Martin", "last_name"=>"Burchardt"}, {"first_name"=>"Christopher H.", "last_name"=>"Lillig"}, {"first_name"=>"Matthias B.", "last_name"=>"Stope"}], "year"=>2015, "source"=>"PLOS ONE", "identifiers"=>{"sgr"=>"84938861645", "doi"=>"10.1371/journal.pone.0130350", "pui"=>"605565636", "pmid"=>"26132846", "issn"=>"1932-6203"}, "id"=>"0bc07fc7-f3a4-3dff-b526-34d7a7d70cfb", "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.", "link"=>"http://www.mendeley.com/research/cold-atmospheric-plasma-treatment-induces-antiproliferative-effects-prostate-cancer-cells-redox-apop-1", "reader_count"=>39, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>7, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Other"=>3, "Student > Master"=>6, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>7, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Other"=>3, "Student > Master"=>6, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>7, "Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>6, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>3, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>4, "Chemistry"=>8, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>7}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Chemistry"=>{"Chemistry"=>8}, "Physics and Astronomy"=>{"Physics and Astronomy"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>6}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2158075"], "description"=>"<p>Living cell number of LNCaP and PC-3 cells after CAP treatment for 10 s. CAP-treated cells were incubated with cell culture medium in the absence of NAC and vitamin C (○ and ●), (A+B) cell culture medium containing 5 mM NAC (□ and ■), and (C+D) cell culture medium containing 100 μM vitamin C (VitC, □ and ■) over a period of 120 h. Cells were counted using a CASY Cell Counter and Analyzer Modell TT (Roche Applied Science) at indicated time points. Results are expressed as the mean ±SD of cell count. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001, as determined by Student’s <i>t</i> test.</p>", "links"=>[], "tags"=>["nac", "gsh", "prostate cancer cells", "tunel", "CAP treatment", "intracellular redox homeostasis", "Annexin V assay", "pc", "ros", "intracellular peroxide levels", "rns", "Cell growth", "Apoptotic Signaling Pathways"], "article_id"=>1470363, "categories"=>["Uncategorised"], "users"=>["Martin Weiss", "Denis Gümbel", "Eva-Maria Hanschmann", "Robert Mandelkow", "Nadine Gelbrich", "Uwe Zimmermann", "Reinhard Walther", "Axel Ekkernkamp", "Axel Sckell", "Axel Kramer", "Martin Burchardt", "Christopher H. Lillig", "Matthias B. Stope"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130350.g006", "stats"=>{"downloads"=>1, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_N_acetylcysteine_NAC_reverses_anti_proliferative_effects_of_cold_atmospheric_plasma_CAP_on_LNCaP_and_PC_3_cells_/1470363", "title"=>"N-acetylcysteine (NAC) reverses anti-proliferative effects of cold atmospheric plasma (CAP) on LNCaP and PC-3 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 03:06:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2158074"], "description"=>"<p>LNCaP and PC-3 cells were CAP treated for 10 sec, fixed with 4% paraformaldehyde for 15 min and stained with 4′,6-diamidino-2-phenylindole (DAPI) for fluorescence analysis. Nuclear parameters area (A, F), perimeter (B,G), major axis (C,H), minor axis (D,I) and brightness per cell (E,J) after DAPI fluorescence of LNCaP and PC-3 cells after CAP and argon (contr) treatment. Incubation with cycloheximide (cyclohex) and its vehicle served as internal positive control for apoptosis. Data are expressed as the mean ±SD. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001, as determined by Student’s <i>t</i> test.</p>", "links"=>[], "tags"=>["nac", "gsh", "prostate cancer cells", "tunel", "CAP treatment", "intracellular redox homeostasis", "Annexin V assay", "pc", "ros", "intracellular peroxide levels", "rns", "Cell growth", "Apoptotic Signaling Pathways"], "article_id"=>1470362, "categories"=>["Uncategorised"], "users"=>["Martin Weiss", "Denis Gümbel", "Eva-Maria Hanschmann", "Robert Mandelkow", "Nadine Gelbrich", "Uwe Zimmermann", "Reinhard Walther", "Axel Ekkernkamp", "Axel Sckell", "Axel Kramer", "Martin Burchardt", "Christopher H. Lillig", "Matthias B. Stope"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130350.g005", "stats"=>{"downloads"=>2, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cold_atmospheric_plasma_CAP_treatment_causes_morphological_changes_to_DNA_and_nucleus_visualized_by_nuclear_morphology_assay_/1470362", "title"=>"Cold atmospheric plasma (CAP) treatment causes morphological changes to DNA and nucleus visualized by nuclear morphology assay.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 03:06:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2158058"], "description"=>"<p>(A) Plasma jet kINPen09 (Neoplas GmbH, Greifswald, Germany), (B) schematic reconstruction of kINPen09 and composition of physical plasma.</p>", "links"=>[], "tags"=>["nac", "gsh", "prostate cancer cells", "tunel", "CAP treatment", "intracellular redox homeostasis", "Annexin V assay", "pc", "ros", "intracellular peroxide levels", "rns", "Cell growth", "Apoptotic Signaling Pathways"], "article_id"=>1470357, "categories"=>["Uncategorised"], "users"=>["Martin Weiss", "Denis Gümbel", "Eva-Maria Hanschmann", "Robert Mandelkow", "Nadine Gelbrich", "Uwe Zimmermann", "Reinhard Walther", "Axel Ekkernkamp", "Axel Sckell", "Axel Kramer", "Martin Burchardt", "Christopher H. Lillig", "Matthias B. Stope"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130350.g001", "stats"=>{"downloads"=>3, "page_views"=>92, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_cold_atmospheric_plasma_CAP_source_/1470357", "title"=>"The cold atmospheric plasma (CAP) source.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 03:06:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2158077"], "description"=>"<p>LNCaP and PC-3 cells were treated with 5 mM NAC for a period of 12 h. Cells were harvested and lysed at different time points. Total GSH levels were analysed in a colorimetric assay using 5,5′-Dithio-bis-(2-Nitrobenzoic acid) (DTNB) as substrate. GSH levels were quantified against GSH standards and are depicted as μmol/mg total protein. 4 h (LNCaP) and 12 h (PC-3) following NAC treatment a significant increase in total GSH levels was detected. Results are expressed as the mean ±SD of cell count.</p>", "links"=>[], "tags"=>["nac", "gsh", "prostate cancer cells", "tunel", "CAP treatment", "intracellular redox homeostasis", "Annexin V assay", "pc", "ros", "intracellular peroxide levels", "rns", "Cell growth", "Apoptotic Signaling Pathways"], "article_id"=>1470365, "categories"=>["Uncategorised"], "users"=>["Martin Weiss", "Denis Gümbel", "Eva-Maria Hanschmann", "Robert Mandelkow", "Nadine Gelbrich", "Uwe Zimmermann", "Reinhard Walther", "Axel Ekkernkamp", "Axel Sckell", "Axel Kramer", "Martin Burchardt", "Christopher H. Lillig", "Matthias B. Stope"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130350.g007", "stats"=>{"downloads"=>3, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Intracellular_glutathione_GSH_levels_following_N_acetylcysteine_NAC_treatment_/1470365", "title"=>"Intracellular glutathione (GSH) levels following N-acetylcysteine (NAC) treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 03:06:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2158060"], "description"=>"<p>LNCaP and PC-3 cells were treated with CAP for 10 s and were cultured for 24 h. Argon treated cells were used as control (contr). Cells were harvested and processed using a FITC Annexin V Apoptosis Detection Kit I (BD Bioscience, Germany) according to manufactures' instructions. 24 h after CAP treatment LNCaP and PC-3 cells showed an increase of phosphatidylserine-bound Annexin V. Data are expressed as the mean ±SD. ***<i>p</i><0.01, as determined by Student’s <i>t</i> test.</p>", "links"=>[], "tags"=>["nac", "gsh", "prostate cancer cells", "tunel", "CAP treatment", "intracellular redox homeostasis", "Annexin V assay", "pc", "ros", "intracellular peroxide levels", "rns", "Cell growth", "Apoptotic Signaling Pathways"], "article_id"=>1470359, "categories"=>["Uncategorised"], "users"=>["Martin Weiss", "Denis Gümbel", "Eva-Maria Hanschmann", "Robert Mandelkow", "Nadine Gelbrich", "Uwe Zimmermann", "Reinhard Walther", "Axel Ekkernkamp", "Axel Sckell", "Axel Kramer", "Martin Burchardt", "Christopher H. Lillig", "Matthias B. Stope"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130350.g003", "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_detection_of_membranous_phosphatidylserine_by_Annexin_V_following_cold_atmospheric_plasma_CAP_exposure_/1470359", "title"=>"Increased detection of membranous phosphatidylserine by Annexin V following cold atmospheric plasma (CAP) exposure.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 03:06:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2158061"], "description"=>"<p>LNCaP and PC-3 cells were treated with CAP for 10 s and were cultured for 4 h or 24 h. Argon treated cells were used as control (contr). Cells were harvested and processed by specific labeling of nuclear DNA fragmentation with a HT TiterTACS Assay Kit (Trevigen, Gaithersburg, USA) according to manufactures' instructions. (A) Nuclear DNA fragmentation of LNCaP and (B) PC-3 cells after 10 sec of CAP treatment (CAP) compared to argon treated controls (contr). Unlabeled control cells (unlabeled contr) served as negative control and nuclease treated cells (nuclease contr) served as positive control, respectively. Data are expressed as the mean ±SD. *<i>p</i><0.05, **<i>p</i><0.01, as determined by Student’s <i>t</i> test.</p>", "links"=>[], "tags"=>["nac", "gsh", "prostate cancer cells", "tunel", "CAP treatment", "intracellular redox homeostasis", "Annexin V assay", "pc", "ros", "intracellular peroxide levels", "rns", "Cell growth", "Apoptotic Signaling Pathways"], "article_id"=>1470360, "categories"=>["Uncategorised"], "users"=>["Martin Weiss", "Denis Gümbel", "Eva-Maria Hanschmann", "Robert Mandelkow", "Nadine Gelbrich", "Uwe Zimmermann", "Reinhard Walther", "Axel Ekkernkamp", "Axel Sckell", "Axel Kramer", "Martin Burchardt", "Christopher H. Lillig", "Matthias B. Stope"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130350.g004", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_LNCaP_and_PC_3_nuclei_following_cold_atmospheric_plasma_CAP_exposure_/1470360", "title"=>"Changes in LNCaP and PC-3 nuclei following cold atmospheric plasma (CAP) exposure.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 03:06:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2158059"], "description"=>"<p>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. *<i>p</i><0.05; ***<i>p</i><0.001, as determined by Student’s <i>t</i> test.</p>", "links"=>[], "tags"=>["nac", "gsh", "prostate cancer cells", "tunel", "CAP treatment", "intracellular redox homeostasis", "Annexin V assay", "pc", "ros", "intracellular peroxide levels", "rns", "Cell growth", "Apoptotic Signaling Pathways"], "article_id"=>1470358, "categories"=>["Uncategorised"], "users"=>["Martin Weiss", "Denis Gümbel", "Eva-Maria Hanschmann", "Robert Mandelkow", "Nadine Gelbrich", "Uwe Zimmermann", "Reinhard Walther", "Axel Ekkernkamp", "Axel Sckell", "Axel Kramer", "Martin Burchardt", "Christopher H. Lillig", "Matthias B. Stope"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130350.g002", "stats"=>{"downloads"=>3, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cold_atmospheric_plasma_CAP_inhibits_cellular_growth_of_human_prostate_cancer_cells_/1470358", "title"=>"Cold atmospheric plasma (CAP) inhibits cellular growth of human prostate cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 03:06:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2158079"], "description"=>"<p>LNCaP and PC-3 cells were treated for 10 s with CAP or argon (contr), respectively. Immediately as well as 1 h after the treatment, cells were treated with the alkylating agent N-ethylmaleimide (NEM) which irreversibly binds to reduced thiol groups prior to cell lysis. The protein levels of cytosolic Prx1 and 2, as well as mitochondrial Prx3 were analysed in cell lysates, as well as the redox state using non reducing SDS Page and Western Blot. A) Representative Prx redox blots of the three analysed peroxidases Prx1, Prx2 and Prx3, showing the monomeric Prx and the during the catalytic mechanism generated oxidized, dimeric form. B) Densitometric quantification of the oxidized Prxs compared to total Prx protein (monomeric and dimeric form).</p>", "links"=>[], "tags"=>["nac", "gsh", "prostate cancer cells", "tunel", "CAP treatment", "intracellular redox homeostasis", "Annexin V assay", "pc", "ros", "intracellular peroxide levels", "rns", "Cell growth", "Apoptotic Signaling Pathways"], "article_id"=>1470367, "categories"=>["Uncategorised"], "users"=>["Martin Weiss", "Denis Gümbel", "Eva-Maria Hanschmann", "Robert Mandelkow", "Nadine Gelbrich", "Uwe Zimmermann", "Reinhard Walther", "Axel Ekkernkamp", "Axel Sckell", "Axel Kramer", "Martin Burchardt", "Christopher H. Lillig", "Matthias B. Stope"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130350.g008", "stats"=>{"downloads"=>3, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cold_atmospheric_plasma_CAP_affects_cellular_peroxiredoxins_Prxs_/1470367", "title"=>"Cold atmospheric plasma (CAP) affects cellular peroxiredoxins (Prxs).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 03:06:20"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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