Mitochondria-Mediated Anticancer Effects of Non-Thermal Atmospheric Plasma.
Non-thermal atmospheric pressure plasma has attracted great interest due to its multiple potential biomedical applications with cancer treatment being among the most urgent. To realize the clinical potential of non-thermal plasma, the exact cellular and molecular mechanisms of plasma effects must be understood. This work aimed at studying the prostate cancer specific mechanisms of non-thermal plasma effects on energy metabolism as a central regulator of cell homeostasis and proliferation. It was found that cancer cells with higher metabolic rate initially are more resistant to plasma treated phosphate-buffered saline (PBS) since the respiratory and calcium sensitive signaling systems were not responsive to plasma exposure. However, dramatic decline of cancer oxidative phosphorylation developed over time resulted in significant progression of cell lethality. The normal prostate cells with low metabolic activity immediately responded to plasma treated PBS by suppression of respiratory functions and sustained elevation of cytosolic calcium. However, over time the normal cells start recovering their mitochondria functions, proliferate and restore the cell population. We found that the non-thermal plasma induced increase in intracellular ROS is of primarily non-mitochondrial origin. The discriminate non-thermal plasma effects hold a promise for clinical cancer intervention.
Department of Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.|Department of Biophysics and Biomedicine, Al-Farabi Kazakh National University, Almaty, Kazakhstan.
Aigul
A
Zhunussova
Department of Electrical and Computer Engineering, Drexel University, Philadelphia, Pennsylvania, United States of America.
Elina A
EA
Vitol
Department of Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
Boris
B
Polyak
Department of Biophysics and Biomedicine, Al-Farabi Kazakh National University, Almaty, Kazakhstan.
Sultan
S
Tuleukhanov
Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Ari D
AD
Brooks
Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Richard
R
Sensenig
Department of Electrical and Computer Engineering, Drexel University, Philadelphia, Pennsylvania, United States of America.
Gary
G
Friedman
Department of Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
Zulfiya
Z
Orynbayeva
D000970:Antineoplastic Agents / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D058626:Plasma Gases / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D058626:Plasma Gases; D017382:Reactive Oxygen Species