Hmox1 Upregulation Is a Mutual Marker in Human Tumor Cells Exposed to Physical Plasma-Derived Oxidants

Bekeschus, Sander; Freund, Eric; Wende, Kristian; Gandhirajan, Rajesh Kumar; Schmidt, Anke

doi:10.3390/antiox7110151

Cited by 32 publications

(25 citation statements)

References 74 publications

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“…Several studies by others and us have observed plasma-induced tumor cell death before [82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98]. Kumar and colleagues observed in several pancreatic cancer cell lines an increase in apoptosis concomitant with downregulation of MAPK7, BCL2, and CHK1 [99].…”

Section: Discussionmentioning

confidence: 94%

Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells

et al. 2019

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Recent advances in melanoma therapy increased median survival in patients. However, death rates are still high, motivating the need of novel avenues in melanoma treatment. Cold physical plasma expels a cocktail of reactive species that have been suggested for cancer treatment. High species concentrations can be used to exploit apoptotic redox signaling pathways in tumor cells. Moreover, an immune-stimulatory role of plasma treatment, as well as plasma-killed tumor cells, was recently proposed, but studies using primary immune cells are scarce. To this end, we investigated the role of plasma-treated murine B16F10 melanoma cells in modulating murine immune cells’ activation and marker profile. Melanoma cells exposed to plasma showed reduced metabolic and migratory activity, and an increased release of danger signals (ATP, CXCL1). This led to an altered cytokine profile with interleukin-1β (IL-1β) and CCL4 being significantly increased in plasma-treated mono- and co-cultures with immune cells. In T cells, plasma-treated melanoma cells induced extracellular signal-regulated Kinase (ERK) phosphorylation and increased CD28 expression, suggesting their activation. In monocytes, CD115 expression was elevated as a marker for activation. In summary, here we provide proof of concept that plasma-killed tumor cells are recognized immunologically, and that plasma exerts stimulating effects on immune cells alone.

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Section: Discussionmentioning

confidence: 94%

Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells

et al. 2019

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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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“…Plasmas are multi-component systems generating UV radiation, visible light, electromagnetic fields, thermal radiation, electrons and ions, and reactive oxygen species (ROS) and reactive nitrogen species (RNS) [2]. 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].…”

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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Hmox1 Upregulation Is a Mutual Marker in Human Tumor Cells Exposed to Physical Plasma-Derived Oxidants

Cited by 32 publications

References 74 publications

Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells

Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells

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

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

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