Mechanistic insights into the impact of Cold Atmospheric Pressure Plasma on human epithelial cell lines

Marlène Dezest,Laurent Chavatte,Luc Garrigues,Damien Quinton,Valérie Planat,Anne-Laure Bulteau,Louis Casteilla,Pascal Descargues,Mylène Camus,Franck Clément,Marion Bourdens,Odile Burlet-Schiltz,Stéphane Arbault

doi:10.1038/srep41163

Abstract

Compelling evidence suggests that Cold Atmospheric Pressure Plasma (CAPP) has potential as a new cancer therapy. However, knowledge about cellular signaling events and toxicity subsequent to plasma treatment is still poorly documented. The aim of this study was to focus on the interaction between 3 different types of plasma (He, He-O2, He-N2) and human epithelial cell lines to gain better insight into plasma-cell interaction. We provide evidence that reactive oxygen and nitrogen species (RONS) are inducing cell death by apoptosis and that the proteasome, a major intracellular proteolytic system which is important for tumor cell growth and survival, is a target of (He or He-N2) CAPP. However, RONS are not the only actors involved in cell death; electric field and charged particles could play a significant role especially for He-O2 CAPP. By differential label-free quantitative proteomic analysis we found that CAPP triggers antioxidant and cellular defense but is also affecting extracellular matrix in keratinocytes. Moreover, we found that malignant cells are more resistant to CAPP treatment than normal cells. Taken together, our findings provide insight into potential mechanisms of CAPP-induced proteasome inactivation and the cellular consequences of these events.

Highlights

One of the most promising applications of the cold atmospheric pressure plasmas (CAPPs) in medicine is associated with cancer therapies especially skin cancer such as melanoma and carcinomas with the highest therapy resistance[1]
We choose epithelial cell lines to gain insight into plasma-cell interaction and to determine which cellular pathways are induced by CAPP treatment in normal and malignant cells
Results of previous studies suggested that cancer cells which are deficient in p-53 are more sensitive to CAPP17

Summary

Introduction

One of the most promising applications of the cold atmospheric pressure plasmas (CAPPs) in medicine is associated with cancer therapies especially skin cancer such as melanoma and carcinomas with the highest therapy resistance[1]. CAPPs are partially ionized gases that are out of thermodynamic equilibrium These excited gases contains free charges (electrons, ions), free radicals, excited molecules and photons (UV), and generate a transient electric field[2,3]. Recent studies have shown that CAPPs preferentially activate various cell death modalities in cancer cell lines compared to their normal counterparts[7,8,9,10]. Alteration in proteasome activity upon CAPP exposure would be expected to significantly impact a number of cellular events, thereby influencing the outcome of cold plasma treatment. We choose epithelial cell lines (human keratinocytes, human fibroblasts, human colorectal carcinoma and skin melanoma) to gain insight into plasma-cell interaction and to determine which cellular pathways are induced by CAPP treatment in normal and malignant cells. Our results demonstrate that plasma treatment (He or He-N2) induced a significant decline in proteasome activity and a gradual cell sensitivity to CAPP

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