Abstract
The antimicrobial, anti-inflammatory and tissue-stimulating effects of cold argon atmospheric plasma (CAAP) accelerate its use in various fields of medicine. Here, we investigated the effects of CAAP at different radiation doses on mesenchymal stem cells (MSCs) and human osteosarcoma (MNNG/HOS) cells. We observed an increase in the growth rate of MSCs at sufficiently low irradiation doses (10–15 min) of CAAP, while the growth of MNNG/HOS cells was slowed down to 41% at the same irradiation doses. Using flow cytometry, we found that these effects are associated with cell cycle arrest and extended death of cancer cells by necrosis. Reactive oxygen species (ROS) formation was detected in both types of cells after 15 min of CAAP treatment. Evaluation of the genes’ transcriptional activity showed that exposure to low doses of CAAP activates the expression of genes responsible for proliferation, DNA replication, and transition between phases of the cell cycle in MSCs. There was a decrease in the transcriptional activity of most of the studied genes in MNNG/HOS osteosarcoma cancer cells. However, increased transcription of osteogenic differentiation genes was observed in normal and cancer cells. The selective effects of low and high doses of CAAP treatment on cancer and normal cells that we found can be considered in terms of hormesis. The low dose of cold argon plasma irradiation stimulated the vital processes in stem cells due to the slight generation of reactive oxygen species. In cancer cells, the same doses evidently lead to the formation of oxidative stress, which was accompanied by a proliferation inhibition and cell death. The differences in the cancer and normal cells’ responses are probably due to different sensitivity to exogenous oxidative stress. Such a selective effect of CAAP action can be used in the combined therapy of oncological diseases such as skin neoplasms, or for the removal of remaining cancer cells after surgical removal of a tumor.
Highlights
Cold atmospheric plasma (CAP) has found its application in medicine as an effective agent for microflora destruction on various surfaces or in liquids [1]
We have shown that cold argon atmospheric plasma (CAAP) stimulates the processes of proliferation in stem cells at the same small doses of irradiation, whereas in cancer cells, it leads to a significant slowdown in proliferation, apoptosis activation, and cell necrosis
The proliferation of cancer MNNG/HOS cells was not accelerated after 10 min of CAAP irradiation in contrast to mesenchymal stem cells (MSCs), but the tendency to inhibition was less pronounced
Summary
Cold atmospheric plasma (CAP) has found its application in medicine as an effective agent for microflora destruction on various surfaces or in liquids [1] This agent can directly affect mammalian cells and tissues and provide a significant reduction in microbial load (for example, on wound surfaces), including multiple antibiotic-resistant bacteria [2]. It has been shown that low doses of CAP irradiation activate the processes of cell proliferation and wound healing [14]. There are virtually no studies showing the efficiency of cold plasma exposure under the same irradiation conditions, using the same generators, but on different cell types. We investigated the sensitivity of normal and cancer human cells to low and high irradiation doses of cold atmospheric argon plasma (CAAP) and under different irradiation modes. The CAAP use would allow this, without damaging normal cells, and with the stimulation of the processes of their proliferation and growth, providing recovery of damaged human tissues after surgical procedures
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