In vitro Demonstration of Cancer Inhibiting Properties from Stratified Self-Organized Micro-Discharge Plasma-Liquid Interface

Experiments have revealed a nontrivial cancer-inhibiting capability of liquid media treated by the plasma jet capable of forming thinly stratified self-organized patterns at a plasma-liquid interface. A pronounced cancer depressing activity towards at least two kinds of human cancer cells, namely breast cancer MDA-MB-231 and human glioblastoma U87 cancer lines, was demonstrated. After a short treatment at the thinly stratified self-organized plasma-liquid interface pattern, the cancer inhibiting media demonstrate well pronounced depression and apoptosis activities towards tumor cells, not achievable without interfacial stratification of plasma jet to thin (of several um) current filaments, which therefore play a pivotal (yet still not completely clear) role in building up the cancer inhibition properties. Moreover, thinly stratified, self-organized interfacial discharge is capable to efficiently control the ROS and RNS concentrations in the cancer-inhibiting media, and in particular, abnormal ROS/RNS ratios not achievable in discharges which do not form stratified thin-filament patterns could be obtained. These results were explained in terms of interaction of thin plasma filaments of the self-organized pattern with gas and liquid, where the unusual interaction conditions (i.e., high surface-to-volume ratios etc.) cause accumulation of ROS, RNS and other species in unusual ratios and concentrations, thus forming potentially efficient anti-cancer cocktail. Our funding could be extremely important for handling the cancer proliferation problem, and hence, it should be brought to light to attract due attention of the researchers and explore the possible potential of this approach in tackling the challenging problem of high cancer-induced mortality and rising morbidity trends.

[1]  D. Auguste,et al.  Pattern-based sensing of triple negative breast cancer cells with dual-ligand cofunctionalized gold nanoclusters. , 2017, Biomaterials.

[2]  J. Trelles Finite Element Methods for Arc Discharge Simulation , 2017 .

[3]  Mark J. Kushner,et al.  Air plasma treatment of liquid covered tissue: long timescale chemistry , 2016 .

[4]  Juan Pablo Trelles,et al.  Pattern formation and self-organization in plasmas interacting with surfaces , 2016 .

[5]  S. Macgregor,et al.  Production characteristics of reactive oxygen/nitrogen species in water using atmospheric pressure discharge plasmas , 2016 .

[6]  M. Keidar,et al.  Effects of cold atmospheric plasma generated in deionized water in cell cancer therapy , 2016, 1607.06775.

[7]  M. Keidar,et al.  The strong anti-glioblastoma capacity of the plasma-stimulated lysine-rich medium , 2016 .

[8]  M. Keidar,et al.  Treatment of gastric cancer cells with nonthermal atmospheric plasma generated in water. , 2016, Biointerphases.

[9]  Wei Zhu,et al.  Synergistic Effect of Cold Atmospheric Plasma and Drug Loaded Core-shell Nanoparticles on Inhibiting Breast Cancer Cell Growth , 2016, Scientific Reports.

[10]  Patrick J. Cullen,et al.  Cytotoxic and mutagenic potential of solutions exposed to cold atmospheric plasma , 2016, Scientific Reports.

[11]  M. Keidar Therapeutic Approaches Based on Plasmas and Nanoparticles , 2016 .

[12]  T. H. Chung,et al.  Cold atmospheric plasma jet-generated RONS and their selective effects on normal and carcinoma cells , 2016, Scientific Reports.

[13]  K. Hensel,et al.  Biological and Chemical Effect of DC Transient Spark Discharge on Escherichia Coli , 2016 .

[14]  Michael Keidar,et al.  Principles of using Cold Atmospheric Plasma Stimulated Media for Cancer Treatment , 2015, Scientific Reports.

[15]  K. Koga,et al.  Influence of ionic liquid and ionic salt on protein against the reactive species generated using dielectric barrier discharge plasma , 2015, Scientific Reports.

[16]  M. Keidar,et al.  Preface to Special Topic: Plasmas for Medical Applications , 2015 .

[17]  V. Sharma,et al.  Effects of Atmospheric Pressure Plasmas on Isolated and Cellular DNA—A Review , 2015, International journal of molecular sciences.

[18]  M. Kushner,et al.  Self-organization of single filaments and diffusive plasmas during a single pulse in dielectric-barrier discharges , 2014 .

[19]  J. Choi,et al.  Effect of additive oxygen gas on cellular response of lung cancer cells induced by atmospheric pressure helium plasma jet , 2014, Scientific Reports.

[20]  S. Uchida,et al.  Influence of oxygen gas on characteristics of self-organized luminous pattern formation observed in an atmospheric dc glow discharge using a liquid electrode , 2014 .

[21]  P G C Almeida,et al.  Self-organization in dc glow microdischarges in krypton: modelling and experiments , 2014 .

[22]  Weidong Zhu,et al.  The missing modes of self-organization in cathode boundary layer discharge in xenon , 2014 .

[23]  Yuhua Wang,et al.  Turning a water and oil insoluble cisplatin derivative into a nanoparticle formulation for cancer therapy. , 2014, Biomaterials.

[24]  Michael Keidar,et al.  Synergistic effect of gold nanoparticles and cold plasma on glioblastoma cancer therapy , 2014 .

[25]  Martin Clupek,et al.  Aqueous-phase chemistry and bactericidal effects from an air discharge plasma in contact with water: evidence for the formation of peroxynitrite through a pseudo-second-order post-discharge reaction of H2O2 and HNO2 , 2014 .

[26]  Y. S. Shin,et al.  Nonthermal plasma induces head and neck cancer cell death: the potential involvement of mitogen-activated protein kinase-dependent mitochondrial reactive oxygen species , 2014, Cell Death and Disease.

[27]  Jürgen Schlegel,et al.  Plasma in Cancer Treatment , 2013 .

[28]  Petr Lukes,et al.  Formation of ROS and RNS in Water Electro-Sprayed through Transient Spark Discharge in Air and their Bactericidal Effects , 2013 .

[29]  P. Bruggeman,et al.  Mechanisms of bacterial inactivation in the liquid phase induced by a remote RF cold atmospheric pressure plasma jet , 2013 .

[30]  D. Pai,et al.  Self-organized pattern formation in helium dielectric barrier discharge cryoplasmas , 2013 .

[31]  M Keidar,et al.  Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy , 2011, British Journal of Cancer.

[32]  M. Mizuno,et al.  Plasma-Activated Medium Selectively Kills Glioblastoma Brain Tumor Cells by Down-Regulating a Survival Signaling Molecule, AKT Kinase , 2011 .

[33]  S. Cavadias,et al.  Analysis of Mechanisms at the Plasma–Liquid Interface in a Gas–Liquid Discharge Reactor Used for Treatment of Polluted Water , 2009 .

[34]  P. Bruggeman,et al.  Anode pattern formation in atmospheric pressure air glow discharges with water anode , 2009 .

[35]  Johan van de Koppel,et al.  Regular pattern formation in real ecosystems. , 2008, Trends in ecology & evolution.

[36]  K. Schoenbach,et al.  Self-organization in cathode boundary layer microdischarges , 2004 .

[37]  M. Cross,et al.  Pattern formation outside of equilibrium , 1993 .

[38]  W. R. Angus The Identification of Molecular Spectra , 1941, Nature.