Search Results
Cold Atmospheric Plasma in the Treatment of Osteosarcoma
2017-9-19, Gümbel, Denis, Bekeschus, Sander, Gelbrich, Nadine, Napp, Matthias, Ekkernkamp, Axel, Kramer, Axel, Stope, Matthias B.
Human osteosarcoma (OS) is the most common primary malignant bone tumor occurring most commonly in adolescents and young adults. Major improvements in disease-free survival have been achieved by implementing a combination therapy consisting of radical surgical resection of the tumor and systemic multi-agent chemotherapy. However, long-term survival remains poor, so novel targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active research. This includes immunotherapy, photodynamic therapy, or treatment with nanoparticles. Cold atmospheric plasma (CAP), a highly reactive (partially) ionized physical state, has been shown to inherit a significant anticancer capacity, leading to a new field in medicine called “plasma oncology.” The current article summarizes the potential of CAP in the treatment of human OS and reviews the underlying molecular mode of action.
xCT (SLC7A11) expression confers intrinsic resistance to physical plasma treatment in tumor cells
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 Kumar
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.