Non-Thermal Plasma, as a New Physicochemical Source, to Induce Redox Imbalance and Subsequent Cell Death in Liver Cancer Cell Lines.
Carcinoma, Hepatocellular
/ drug therapy
Cell Death
/ drug effects
Down-Regulation
/ drug effects
Gene Expression Regulation, Neoplastic
/ drug effects
Hep G2 Cells
Humans
Liver Neoplasms
/ drug therapy
Oxidation-Reduction
/ drug effects
Plasma Gases
/ pharmacology
Reactive Oxygen Species
/ metabolism
Tumor Suppressor Protein p53
/ biosynthesis
Apoptosis, Non-thermal plasma
Oxidative stress
Reactive oxygen species
Stress resistance
p53
Journal
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
ISSN: 1421-9778
Titre abrégé: Cell Physiol Biochem
Pays: Germany
ID NLM: 9113221
Informations de publication
Date de publication:
2019
2019
Historique:
received:
18
09
2018
accepted:
10
01
2019
entrez:
22
2
2019
pubmed:
23
2
2019
medline:
9
3
2019
Statut:
ppublish
Résumé
Alteration of cancer cell redox status has been recognized as a promising therapeutic implication. In recent years, the emerged field of non-thermal plasma (NTP) has shown considerable promise in various biomedical applications, including cancer therapy. However, understanding the molecular mechanisms procuring cellular responses remains incomplete. Thus, the aim of this study was a rigorous biochemical analysis of interactions between NTP and liver cancer cells. The concept was validated using three different cell lines. We provide several distinct lines of evidence to support our findings; we use various methods (epifluorescent and confocal microscopy, clonogenic and cytotoxicity assays, Western blotting, pharmacological inhibition studies, etc.). We assessed the influence of NTP on three human liver cancer cell lines (Huh7, Alexander and HepG2). NTP treatment resulted in higher anti-proliferative effect against Alexander and Huh7 relative to HepG2. Our data clearly showed that the NTP-mediated alternation of mitochondrial membrane potential and dynamics led to ROS-mediated apoptosis in Huh7 and Alexander cells. Interestingly, plasma treatment resulted in p53 down-regulation in Huh7 cells. High levels of Bcl-2 protein expression in HepG2 resulted in their resistance in response to oxidative stress- mediated by plasma. We show thoroughly time- and dose-dependent kinetics of ROS accumulation in HCC cells. Furthermore, we show nuclear compartmentalization of the superoxide anion triggered by NTP. NTP induced apoptotic death in Huh7 liver cancer cells via simultaneous downregulation of mutated p53, pSTAT1 and STAT1. Contrary, hydrogen peroxide treatment results in autophagic cell death. We disclosed detailed mechanisms of NTP-mediated alteration of redox signalling in liver cancer cells.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
Alteration of cancer cell redox status has been recognized as a promising therapeutic implication. In recent years, the emerged field of non-thermal plasma (NTP) has shown considerable promise in various biomedical applications, including cancer therapy. However, understanding the molecular mechanisms procuring cellular responses remains incomplete. Thus, the aim of this study was a rigorous biochemical analysis of interactions between NTP and liver cancer cells.
METHODS
METHODS
The concept was validated using three different cell lines. We provide several distinct lines of evidence to support our findings; we use various methods (epifluorescent and confocal microscopy, clonogenic and cytotoxicity assays, Western blotting, pharmacological inhibition studies, etc.).
RESULTS
RESULTS
We assessed the influence of NTP on three human liver cancer cell lines (Huh7, Alexander and HepG2). NTP treatment resulted in higher anti-proliferative effect against Alexander and Huh7 relative to HepG2. Our data clearly showed that the NTP-mediated alternation of mitochondrial membrane potential and dynamics led to ROS-mediated apoptosis in Huh7 and Alexander cells. Interestingly, plasma treatment resulted in p53 down-regulation in Huh7 cells. High levels of Bcl-2 protein expression in HepG2 resulted in their resistance in response to oxidative stress- mediated by plasma.
CONCLUSION
CONCLUSIONS
We show thoroughly time- and dose-dependent kinetics of ROS accumulation in HCC cells. Furthermore, we show nuclear compartmentalization of the superoxide anion triggered by NTP. NTP induced apoptotic death in Huh7 liver cancer cells via simultaneous downregulation of mutated p53, pSTAT1 and STAT1. Contrary, hydrogen peroxide treatment results in autophagic cell death. We disclosed detailed mechanisms of NTP-mediated alteration of redox signalling in liver cancer cells.
Substances chimiques
Plasma Gases
0
Reactive Oxygen Species
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
119-140Subventions
Organisme : Academy of Sciences of the Czech Republic
Pays : Czech Republic
Organisme : Institute for Clinical and Experimental Medicine
ID : IN 00023001
Pays : Czech Republic
Organisme : European Structural and Investment Funds
Pays : European Union
Organisme : Czech Ministry of Education, Youth and Sports
ID : SOLID21 - CZ.02.1.01/0.0/0.0/16_019/0000760
Pays : Czech Republic
Organisme : The Ministry of Industry and Trade
ID : FV10081
Pays : Czech Republic
Informations de copyright
© Copyright by the Author(s). Published by Cell Physiol Biochem Press.
Déclaration de conflit d'intérêts
The authors do not have financial interests or conflicts.