xCT (SLC7A11) expression confers intrinsic resistance to physical plasma treatment in tumor cells

Publication date: Available online 3 January 2020Source: Redox BiologyAuthor(s): Sander Bekeschus, Sebastian Eisenmann, Sanjeev Kumar Sagwal, Gabriella Pasqual-Melo, Juliane Moritz, Yana Bodnar, Juliane Moritz, Broder Poschkamp, Ingo Stoffels, Steffen Emmert, Thomas von Woedtke, Madesh Muniswamy, Klaus-Dieter Weltmann, Rajesh Kumar GandhirajanAbstractCold 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 toget...

Source: Redox Biology - January 5, 2020 Category: Biology Source Type: research