Physical plasma-triggered ROS induces tumor cell death upon cleavage of HSP90 chaperone

Bekeschus, Sander; Lippert, Maxi; Diepold, Kristina; Chiosis, Gabriela; Seufferlein, Thomas; Azoitei, Ninel

doi:10.1038/s41598-019-38580-0

Cited by 41 publications

(42 citation statements)

References 39 publications

(46 reference statements)

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“…[ 51 ] For MTX, however, it is established that such NFκB activation is a consequence of drug‐induced DNA double‐strand breaks and apoptosis. [ 52 ] With regard to ICD, HSP90 can also inhibit cell death [ 53 ] through interaction with Akt via NFκB‐mediated apoptosis inhibition. [ 54 ] In DCs, phosphorylation of NFκB through DAMPs and TLR4 is a critical mechanism of antitumor activity of these cells.…”

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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“…Medical gas plasma technology recently gained attention due to its antitumor activity against many types of cancers [4][5][6]. Specifically, plasma was shown to inactivate, for instance, malignant melanoma [7], squamous cell carcinoma [5,8], lung cancer [9], colon cancer [10], pancreatic cancer [11], osteosarcoma [12], glioblastoma [13], and hepatocellular carcinoma [14].…”

Section: Introductionmentioning

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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“…Several groups, including us, have previously demonstrated anti-tumor effects with physical plasma treatment [14][15][16]. Some studies already highlighted an added value when combining direct plasma treatment with chemotherapeutic [17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Gas Plasma-Conditioned Ringer’s Lactate Enhances the Cytotoxic Activity of Cisplatin and Gemcitabine in Pancreatic Cancer In Vitro and In Ovo

Liedtke

Freund

Hermes

et al. 2020

Cancers

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Pancreatic cancer is one of the most aggressive tumor entities. Diffuse metastatic infiltration of vessels and the peritoneum restricts curative surgery. Standard chemotherapy protocols include the cytostatic drug gemcitabine with limited efficacy at considerable toxicity. In search of a more effective and less toxic treatment modality, we tested in human pancreatic cancer cells (MiaPaca and PaTuS) a novel combination therapy consisting of cytostatic drugs (gemcitabine or cisplatin) and gas plasma-conditioned Ringer’s lactate that acts via reactive oxygen species. A decrease in metabolic activity and viability, change in morphology, and cell cycle arrest was observed in vitro. The combination treatment was found to be additively toxic. The findings were validated utilizing an in ovo tumor model of solid pancreatic tumors growing on the chorion-allantois membrane of fertilized chicken eggs (TUM-CAM). The combination of the drugs (especially cisplatin) with the plasma-conditioned liquid significantly enhanced the anti-cancer effects, resulting in the induction of cell death, cell cycle arrest, and inhibition of cell growth with both of the cell lines tested. In conclusion, our novel combination approach may be a promising new avenue to increase the tolerability and efficacy of locally applied chemotherapeutic in diffuse metastatic peritoneal carcinomatosis of the pancreas.

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Physical plasma-triggered ROS induces tumor cell death upon cleavage of HSP90 chaperone

Cited by 41 publications

References 39 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

Gas Plasma-Conditioned Ringer’s Lactate Enhances the Cytotoxic Activity of Cisplatin and Gemcitabine in Pancreatic Cancer In Vitro and In Ovo

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