Cold atmospheric plasma induces apoptosis of melanoma cells via Sestrin2‐mediated nitric oxide synthase signaling

Abstract

Cold atmospheric plasma (CAP) represents a promising therapy for selectively cancer killing. However, the mechanism of CAP-induced cancer cell death remains unclear. Here, we identified the tumor necrosis factor-family members, especially Fas, and overloaded intracellular nitric oxide participated in CAP induced apoptosis in A375 and A875 melanoma cell lines, which was known as extrinsic apoptosis pathway. This progress was mediated by antagonistic protein of reactive oxygen species, Sestrin2. The over expression of Sestrin2 induced by plasma treatment resulted in phosphorylation of p38 mitogen-activated protein kinase (MAPK), followed by increased expression of nitric oxide synthase (iNOS), Fas and Fas ligand. Depletion of Sestrin2 reduced iNOS and Fas expression, which was associated with reduction of plasma-induced apoptosis. In contrast, inhibition of iNOS activity and phosphorylation of p38 did not alter Sestrin2 expression in plasma-treated melanoma cells. Taken together, cold atmospheric plasma increases Sestrin2 expression and further activates downstream iNOS, Fas and p38 MAPK signaling to induce apoptosis of melanoma cell lines. These findings suggest a previously unrecognized mechanism in melanoma cells response to cold atmospheric plasma therapy.

On a heavy path – determining cold plasma-derived short-lived species chemistry using isotopic labelling

“…[16][17][18][19] High intensity treatment results in the shutdown of cellular processes and cell death by apoptosis or necrosis-like processes. 20,21 These effects, especially in combination with immune cell modulation, are currently investigated for cancer treatment. [22][23][24][25] Medical plasmas are multicomponent systems containing electrons, ions, electric elds, and a multiplicity of reactive oxygen and nitrogen species (ROS/RNS).…”

Cold atmospheric plasma promotes different types of superficial skin erosion wounds healing

“…Cold atmospheric plasma (CAP) is an ionised gas that is recognised as the fourth physical state of nature, and its composition includes ions, electrons, electric emissions, thermal emissions, radicals, and bioactive molecules . A more in‐depth look demonstrates the capacities of CAP with respect to promoting wound healing, accelerating blood coagulation, killing pathogenic microorganisms, and even killing tumour cells selectively in vitro with little damage to normal cells . Current literature shows that CAP has an effect on common resistant pathogenic microorganisms on human skin, such as Staphylococcus aureus and fungi .…”

Genome-Wide Comparison of the Target Genes of the Reactive Oxygen Species and Non-Reactive Oxygen Species Constituents of Cold Atmospheric Plasma in Cancer Cells

“…However, the target genes of CAP were identified just by examining a single or a few genes in most studies. Previous studies reported that SESN2 and HMOX1 were upregulated in melanoma and lymphoma cells by CAP, leading to the increase of apoptosis [19,20], whereas HSP90 and MMP-9 were downregulated in breast and colon cancer cells, leading to death or growth inhibition of tumor cells [21,22]. These deregulation processes were found to increase apoptosis or inhibit cell proliferation.…”