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

Bekeschus, Sander; Eisenmann, Sebastian; Sagwal, Sanjeev Kumar; Bodnar, Yana; Moritz, Juliane; Poschkamp, Broder; Stoffels, Ingo; Emmert, Steffen; Madesh, Muniswamy; Weltmann, K.‐D.; Woedtke, Thomas von; Gandhirajan, Rajesh Kumar

doi:10.1016/j.redox.2019.101423

Cited by 48 publications

(39 citation statements)

References 63 publications

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“…However, while the physical modalities mentioned generate ROS in the interior of cells, gas plasma treatment adds ROS from the outside with mechanisms and redox‐chemical reaction pathways only starting to be understood as of now. [ 78–80 ] Due to the mechanism of action, gas plasma produced ROS may only act in a localized manner but not systemically.…”

Section: Discussionmentioning

confidence: 99%

Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion

et al. 2020

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Medical technologies from physics are imperative in the diagnosis and therapy of many types of diseases. In 2013, a novel cold physical plasma treatment concept was accredited for clinical therapy. This gas plasma jet technology generates large amounts of different reactive oxygen and nitrogen species (ROS). Using a melanoma model, gas plasma technology is tested as a novel anticancer agent. Plasma technology derived ROS diminish tumor growth in vitro and in vivo. Varying the feed gas mixture modifies the composition of ROS. Conditions rich in atomic oxygen correlate with killing activity and elevate intratumoral immune‐infiltrates of CD8+ cytotoxic T‐cells and dendritic cells. T‐cells from secondary lymphoid organs of these mice stimulated with B16 melanoma cells ex vivo show higher activation levels as well. This correlates with immunogenic cancer cell death and higher calreticulin and heat‐shock protein 90 expressions induced by gas plasma treatment in melanoma cells. To test the immunogenicity of gas plasma treated melanoma cells, 50% of mice vaccinated with these cells are protected from tumor growth compared to 1/6 and 5/6 mice negative control (mitomycin C) and positive control (mitoxantrone), respectively. Gas plasma jet technology is concluded to provide immunoprotection against malignant melanoma both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion

et al. 2020

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“…Tumor-toxic injections with plasma-treated liquids have been recently demonstrated in vivo using a model of pancreatic cancer [88]. Finally, another timely question is whether plasma treatment might be able to revert chemotherapeutic resistance, but apart from first studies on drug-transporter expression in cancer cells after plasma treatment [89,90], such studies are yet awaited to come.…”

Section: Discussionmentioning

confidence: 99%

Gas Plasma-Treated Prostate Cancer Cells Augment Myeloid Cell Activity and Cytotoxicity

et al. 2020

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Despite recent improvements in cancer treatment, with many of them being related to foster antitumor immunity, tumor-related deaths continue to be high. Novel avenues are needed to complement existing therapeutic strategies in oncology. Medical gas plasma technology recently gained attention due to its antitumor activity. Gas plasmas act via the local deposition of a plethora of reactive oxygen species (ROS) that promote the oxidative cancer cell death. The immunological consequences of plasma-mediated tumor cell death are only poorly understood, however. To this end, we exposed two prostate cancer cell lines (LNCaP, PC3) to gas plasma in vitro, and investigated the immunomodulatory effects of the supernatants in as well as of direct co-culturing with two human myeloid cell lines (THP-1, HL-60). After identifying the cytotoxic action of the kINPen plasma jet, the supernatants of plasma-treated prostate cancer cells modulated myeloid cell-related mitochondrial ROS production and their metabolic activity, proliferation, surface marker expression, and cytokine release. Direct co-culture amplified differentiation-like surface marker expression in myeloid cells and promoted their antitumor-toxicity in the gas plasma over the untreated control conditions. The results suggest that gas plasma-derived ROS not only promote prostate cancer cell death but also augment myeloid cell activity and cytotoxicity.

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“…The latter play a crucial role in mediating the plasma effects in cells [3][4][5] by mediating oxidative modifications [6][7][8] to induce signaling pathways [9][10][11]. First discovered as a new tool for disinfection and wound healing [12][13][14], plasma also demonstrates cytotoxicity towards cancer cells [15][16][17]. A range of cellular responses have been found, including apoptosis, growth inhibition, cell cycle arrest, as well as cytoskeletal and mitochondrial damage [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Combination Treatment with Cold Physical Plasma and Pulsed Electric Fields Augments ROS Production and Cytotoxicity in Lymphoma

Wolff

Kolb

Weltmann

et al. 2020

Cancers

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New approaches in oncotherapy rely on the combination of different treatments to enhance the efficacy of established monotherapies. Pulsed electric fields (PEFs) are an established method (electrochemotherapy) for enhancing cellular drug uptake while cold physical plasma is an emerging and promising anticancer technology. This study aimed to combine both technologies to elucidate their cytotoxic potential as well as the underlying mechanisms of the effects observed. An electric field generator (0.9–1.0 kV/cm and 100-μs pulse duration) and an atmospheric pressure argon plasma jet were employed for the treatment of lymphoma cell lines as a model system. PEF but not plasma treatment induced cell membrane permeabilization. Additive cytotoxicity was observed for the metabolic activity and viability of the cells while the sequence of treatment in the combination played only a minor role. Intriguingly, a parallel combination was more effective compared to a 15-min pause between both treatment regimens. A combination effect was also found for lipid peroxidation; however, none could be observed in the cytosolic and mitochondrial reactive oxygen species (ROS) production. The supplementation with either antioxidant, a pan-caspase-inhibitor or a ferroptosis inhibitor, all partially rescued lymphoma cells from terminal cell death, which contributes to the mechanistic understanding of this combination treatment.

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

Cited by 48 publications

References 63 publications

Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion

Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion

Gas Plasma-Treated Prostate Cancer Cells Augment Myeloid Cell Activity and Cytotoxicity

Combination Treatment with Cold Physical Plasma and Pulsed Electric Fields Augments ROS Production and Cytotoxicity in Lymphoma

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