The sensitivity of melanoma towards plasma-treated liquids is determined by its intracellular ROS level

Abstract

The recent development of cold atmospheric plasma (CAP) paved the way for new approaches in the treatment of cancer [1]. Plasma generates various components among which reactive oxygen and nitrogen species (RONS) are hypothesized to mediate the cytotoxic effects observed in biological systems [2]. Several studies have indicated that CAP can selectively target cancer cells, which partly may be explained by the difference in ROS levels between normal and aberrant cells [3]. Melanoma is the deadliest type of skin cancer, mainly because of its great metastatic potential [4]. Melanoma is derived from pigment-producing melanocytes in the basal layers of the epidermis of the skin. Cells from melanocytic origin are under a continuous oxidative stress [5]. These cells therefore have acquired a highly effective antioxidant network which might explain why melanomas are in general resistant to therapies that aim to augment hypoxia-induced apoptosis [6]. Recently, it was discovered that melanocytes express Cytoglobin (Cygb) at a high level [7]. Cygb has been proposed to play a cytoprotective role as a ROS-scavenger and tumor suppressor. In melanoma, the transition from melanocytes is frequently accompanied by a loss of Cygb expression. Whether Cygb is downregulated in melanocyte-to-melanoma transition may influence tumor malignancy and the efficacy of cancer treatments. Recently, in our lab, the selectivity of CAP-treated Phosphate Buffered Saline (pPBS) was investigated in two melanoma cell lines (A357 & Malme3M), and one normal cell line (Primary Melanocyte). Flow cytometric analysis showed that pPBS can induce apoptotic cell death in a selective way, whereby the sensitivity of cells towards pPBS seems to be correlated with their intrinsic intracellular ROS level. Moreover, preliminary data suggests that cells with high Cygb expression are more resistant to pPBS than cells with low expression. As proteins are the main facilitators of biological functions, one could hypothesize that plasma-protein interactions will be key determinants of the cell’s faith after plasma treatment. Therefore, we are currently investigating the effects of plasma-induced RONS on recombinant human Cygb, which might contribute to a better understanding of the above-mentioned postulated functions of the Cygb.