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- ItemInvestigating the Mutagenicity of a Cold Argon-Plasma Jet in an HET-MN Model(San Francisco, California, US : PLOS, 2016) Kluge, Susanne; Bekeschus, Sander; Bender, Claudia; Benkhai, Hicham; Sckell, Axel; Below, Harald; Stope, Matthias B.; Kramer, Axel; Yousfi, MohammedObjective: So-called cold physical plasmas for biomedical applications generate reactive oxygen and nitrogen species and the latter can trigger DNA damage at high concentrations. Therefore, the mutagenic risks of a certified atmospheric pressure argon plasma jet (kINPen MED) and its predecessor model (kINPen 09) were assessed. Methods: Inner egg membranes of fertilized chicken eggs received a single treatment with either the kINPen 09 (1.5, 2.0, or 2.5 min) or the kINPen MED (3, 4, 5, or 10 min). After three days of incubation, blood smears (panoptic May-Grünwald-Giemsa stain) were performed, and 1000 erythrocytes per egg were evaluated for the presence of polychromatic and normochromic nuclear staining as well as nuclear aberrations and binucleated cells (hen’s egg test for micronuclei induction, HET-MN). At the same time, the embryo mortality was documented. For each experiment, positive controls (cyclophosphamide and methotrexate) and negative controls (NaCl-solution, argon gas) were included. Additionally, the antioxidant potential of the blood plasma was assessed by ascorbic acid oxidation assay after treatment. Results: For both plasma sources, there was no evidence of genotoxicity, although at the longest plasma exposure time of 10 min the mortality of the embryos exceeded 40%. The antioxidant potential in the egg’s blood plasma was not significantly reduced immediately (p = 0.32) or 1 h (p = 0.19) post exposure to cold plasma. Conclusion: The longest plasma treatment time with the kINPen MED was 5–10 fold above the recommended limit for treatment of chronic wounds in clinics. We did not find mutagenic effects for any plasma treatment time using the either kINPen 09 or kINPen MED. The data provided with the current study seem to confirm the lack of a genotoxic potential suggesting that a veterinary or clinical application of these argon plasma jets does not pose mutagenic risks.
- ItemPhysical plasma-triggered ROS induces tumor cell death upon cleavage of HSP90 chaperone([London] : Macmillan Publishers Limited, part of Springer Nature, 2019) Bekeschus, Sander; Lippert, Maxi; Diepold, Kristina; Chiosis, Gabriela; Seufferlein, Thomas; Azoitei, NinelHSP90 is a ubiquitously expressed molecular chaperone implicated in the correct folding and maturation of a plethora of proteins including protein kinases and transcription factors. While disruption of chaperone activity was associated with augmented cancer cell death and decreased tumor growth both in vitro and in vivo, the regulation of HSP90 is not clearly understood. Here we report that treatment of cancer cells with cold physical plasma, an emerging and less aggressive tumor therapy, resulted in ROS generation which subsequently triggered the cleavage of HSP90. Notably, cleavage of HSP90 was followed by the degradation of PKD2, a crucial regulator of tumor growth and angiogenesis. Pre-sensitization of cancer cells with subliminal doses of PU-H71, an HSP90 inhibitor currently under clinical evaluation, followed by treatment with cold-plasma, synergistically and negatively impacted on the viability of cancer cells. Taken together, cold-plasma can be used in conjunction with pharmacologic treatment in order to target the expression and activity of HSP90 and the downstream client proteins implicated in various cancer cell capabilities.