Cold atmospheric plasma, a new strategy to induce senescence in melanoma cells

Abstract

Over the past few years, the application of cold atmospheric plasma (CAP) in medicine has developed into an innovative field of research of rapidly growing importance. One promising new medical application of CAP is cancer treatment. Different studies revealed that CAP may potentially affect the cell cycle and cause cell apoptosis or necrosis in tumor cells dependent on the CAP device and doses. In this study, we used a novel hand-held and battery-operated CAP device utilizing the surface micro discharge (SMD) technology for plasma production in air and consequently analysed dose-dependent CAP treatment effects on melanoma cells. After 2 min of CAP treatment, we observed irreversible cell inactivation. Phospho-H2AX immunofluorescence staining and Flow cytometric analysis demonstrated that 2 min of CAP treatment induces DNA damage, promotes induction of Sub-G1 phase and strongly increases apoptosis. Further, protein array technology revealed induction of pro-apoptotic events like p53 and Rad17 phosphorylation of Cytochrome c release and activation of Caspase-3. Interestingly, using lower CAP doses with 1 min of treatment, almost no apoptosis was observed but long-term inhibition of proliferation. H3K9 immunofluorescence, SA-ß-Gal staining and p21 expression revealed that especially these low CAP doses induce senescence in melanoma cells. In summary, we observed differences in induction of apoptosis or senescence of tumor cells in respond to different CAP doses using a new CAP device. The mechanism of senescence with regard to plasma therapy was so far not described previously and is of great importance for therapeutic application of CAP.

Cold Atmospheric Plasma: methods of production and application in dentistry and oncology

“…Cold atmospheric plasma can be used as a new strategy to induce senescence in melanoma cells [135]. Some researchers used a ‘miniFlat-Plaster’ that uses the flexible and scalable Surface Micro Discharge (SMD) technology for plasma production in air.…”

Non‐equilibrium atmospheric pressure plasmas modulate cell cycle‐related gene expressions in melanocytic tumors of RET‐transgenic mice

“…Previous studies have showed that the plasma irradiation is effective for melanoma therapy in vitro (12)(13)(14). To our knowledge, however, information about melanoma therapy by NEAPPs in vivo has not been presented.…”

Plasma-activated medium induces A549 cell injury via a spiral apoptotic cascade involving the mitochondrial–nuclear network

“…These relatively short-lived RONS produced in media by plasma irradiation may be converted to other relatively long-lived species such as hydrogen peroxide (H 2 O 2 ), nitrate/nitrite (NO x ), and other uncertain species, which endow PAM with high and sustainable reactivity [13,16,17]. RONS are known to induce apoptosis via several signaling cascades including mitogen-activated protein kinase and phosphatidylinositol-3-kinase-Akt [8,18,19]. However, the mechanisms underlying the effects of PAM on cancer cells have not yet been elucidated in detail.…”