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

Sander Bekeschus, Sebastian Eisenmann, Sanjeev Kumar Sagwal, Yana Bodnar, Juliane Moritz, Broder Poschkamp, Ingo Stoffels, Steffen Emmert, Muniswamy Madesh, Klaus Dieter Weltmann, Thomas von Woedtke, Rajesh Kumar Gandhirajan

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Cold 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.

Original languageEnglish (US)
Article number101423
JournalRedox Biology
Volume30
DOIs
StatePublished - Feb 2020

Keywords

  • Cancer
  • Glutathione
  • Melanoma
  • Plasma medicine
  • kINPen

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'xCT (SLC7A11) expression confers intrinsic resistance to physical plasma treatment in tumor cells'. Together they form a unique fingerprint.

Cite this