Abstract

Hydrogen peroxide (H2O2) is an important signaling molecule in cancer cells. However, the significant secretion of H2O2 by cancer cells have been rarely observed. Cold atmospheric plasma (CAP) is a near room temperature ionized gas composed of neutral particles, charged particles, reactive species, and electrons. Here, we first demonstrated that breast cancer cells and pancreatic adenocarcinoma cells generated micromolar level H2O2 during just 1 min of direct CAP treatment on these cells. The cell-based H2O2 generation is affected by the medium volume, the cell confluence, as well as the discharge voltage. The application of cold atmospheric plasma (CAP) in cancer treatment has been intensively investigated over the past decade. Several cellular responses to CAP treatment have been observed including the consumption of the CAP-originated reactive species, the rise of intracellular reactive oxygen species, the damage on DNA and mitochondria, as well as the activation of apoptotic events. This is a new previously unknown cellular response to CAP, which provides a new prospective to understand the interaction between CAP and cells in vitro and in vivo. The short-lived reactive species in CAP may activate cells in vivo to generate long-lived reactive species such as H2O2, which may trigger immune attack on tumorous tissues via the H2O2-mediated lymphocyte activation.

Highlights

  • Cold atmospheric plasma (CAP), a near room temperature ionized gas composed of charged particles, neutral particles and electrons, has shown its promising application in cancer treatment over the past decade[6,7,8,9,10,11]

  • We first provide the experimental evidence that the 1 min of CAP treatment can trigger μM level cancer cell-based H2O2 generation through comparing the H2O2 generation in the CAP-treated cell-free medium and the CAP-treated cancer cells covered by a thin layer of medium

  • We investigated the evolution of extracellular H2O2 in PSM and H2O2-Dulbecco’s modified Eagle’s medium (DMEM), which have been used to culture cancer cell lines

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Summary

Introduction

Cold atmospheric plasma (CAP), a near room temperature ionized gas composed of charged particles, neutral particles and electrons, has shown its promising application in cancer treatment over the past decade[6,7,8,9,10,11]. For the direct CAP treatment in vitro, a thin layer of cell culture medium is used to cover cancer cells[36] This medium layer facilitates the transition of the reactive species in the gas phase into the dissolved reactive species in medium[36]. The direct CAP treatment can be regarded essentially the same as the indirect CAP treatment if we assume that the formed long-lived reactive species such as H2O2, NO2−, ONOO− in the CAP-treated solution is the sole factor leading to decreased tumor cell viability. We first provide the experimental evidence that the 1 min of CAP treatment can trigger μM level cancer cell-based H2O2 generation through comparing the H2O2 generation in the CAP-treated cell-free medium and the CAP-treated cancer cells covered by a thin layer of medium Such cell-based H2O2 generation can be regulated by controlling the volume of the medium layer, the cell confluence, as well as the discharge voltage. This is a novel perspective to understand the interaction between CAP and cells

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