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- ItemCold physical plasma-induced oxidation of cysteine yields reactive sulfur species (RSS)(Amsterdam [u.a.] : Elsevier, 2019) Bruno, Giuliana; Heusler, Thea; Lackmann, Jan-Wilm; Woedtke, Thomas von; Weltmann, Klaus-Dieter; Wende, KristianPurpose: Studying plasma liquid chemistry can reveal insights into their biomedical effects, i.e. to understand the direct and indirect processes triggered by the treatment in a model or clinical application. Due to the reactivity of the sulfur atom, thiols are potential targets for plasma- derived reactive species. Being crucial for protein function and redox signaling pathways, their controllable modification would allow expanding the application range. Additionally, models to control and standardize CAP sources are desired tools for plasma source design. Methods: Cysteine, a ubiquitous amino acid, was used as a tracer compound to scavenge the reactive species produced by an argon plasma jet (kINPen). The resulting product pattern was identified via high-resolution mass spectrometry. The Ellman´s assay was used to screen CAP derived thiol consumption, and long-lived species deposition (hydrogen peroxide, nitrite, nitrate) was monitored in relation to the presence of cysteine. Results: The intensity of cysteine oxidation increased with treatment time and availability of oxygen in the feed gas. A range of products from cysteine was identified, in part indicative for certain treatment conditions. Several non-stable products occur transiently during the plasma treatment. Bioactive reactive sulfur species (RSS) have been found for mild treatment conditions, such as cysteine sulfoxides and cysteine-S-sulfonate. Considering the number of cysteine molecules in the boundary layer and the achieved oxidation state, short-lived species dominate in cysteine conversion. In addition, a boundary layer depletion of the tracer was observed. Conclusion: Translating these data into the in-vivo application, strong direct oxidation of protein thiol groups with subsequent changes in protein biochemistry must be considered. Plasma-derived RSS may in part contribute to the observed biomedical effects of CAP. Care must be taken to control the discharge parameter tightly as chemical dynamics at or in the liquid are subject to change easily. © 2019
- ItemxCT (SLC7A11) expression confers intrinsic resistance to physical plasma treatment in tumor cells(Amsterdam [u.a.] : Elsevier, 2020) Bekeschus, Sander; Eisenmann, Sebastian; Sagwal, Sanjeev Kumar; Bodnar, Yana; Moritz, Juliane; Poschkamp, Broder; Stoffels, Ingo; Emmert, Steffen; Madesh, Muniswamy; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Gandhirajan, Rajesh KumarCold physical plasma is a partially ionized gas investigated as a new anticancer tool in selectively targeting cancer cells in monotherapy or in combination with therapeutic agents. Here, we investigated the intrinsic resistance mechanisms of tumor cells towards physical plasma treatment. When analyzing the dose-response relationship to cold plasma-derived oxidants in 11 human cancer cell lines, we identified four 'resistant' and seven 'sensitive' cell lines. We observed stable intracellular glutathione levels following plasma treatment only in the 'resistant' cell lines indicative of altered antioxidant mechanisms. Assessment of proteins involved in GSH metabolism revealed cystine-glutamate antiporter xCT (SLC7A11) to be significantly more abundant in the 'resistant' cell lines as compared to 'sensitive' cell lines. This decisive role of xCT was confirmed by pharmacological and genetic inhibition, followed by cold physical plasma treatment. Finally, microscopy analysis of ex vivo plasma-treated human melanoma punch biopsies suggested a correlation between apoptosis and basal xCT protein abundance. Taken together, our results demonstrate that xCT holds the potential as a biomarker predicting the sensitivity of tumor cells towards plasma treatment.