Mitochondria-Mediated Anticancer Effects of Non-Thermal Atmospheric Plasma.

Aigul Zhunussova,Ari D Brooks,Richard Sensenig,Zulfiya Orynbayeva,Boris Polyak,Gary Friedman,Sultan Tuleukhanov,Elina A Vitol,Dhyan Chandra

doi:10.1371/journal.pone.0156818

Abstract

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.

Highlights

Prostate cancer is the second leading cause of death from cancer in North American and European men [1]
Plasma exerts distinct cytotoxicity on prostate cancer and normal cells To assess the effects of plasma on metabolism of metastatic prostate DU145 cells and their normal counterparts, human primary prostate epithelial cells PrEC, first we determined the plasma doses that are potentially cytotoxic
We validated the effects of plasma treated phosphate-buffered saline (PBS) on cell proliferative activity

Summary

Introduction

Prostate cancer is the second leading cause of death from cancer in North American and European men [1]. It is a slow growing cancer, but as many other types of cancer, it is generally incurable once it reaches the metastatic stage [2]. Existing chemotherapies have severe side effects and do not provide a cure for advanced stages of the disease. There is an urgent need for novel medical approaches for treating tumor types which tend to develop resistance to chemo- and radiation therapies [3]. PLOS ONE | DOI:10.1371/journal.pone.0156818 June 6, 2016

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