scholarly journals Cold Atmospheric Plasma Increases Temozolomide Sensitivity of Three-Dimensional Glioblastoma Spheroids via Oxidative Stress-Mediated DNA Damage

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1780
Author(s):  
Priyanka Shaw ◽  
Naresh Kumar ◽  
Angela Privat-Maldonado ◽  
Evelien Smits ◽  
Annemie Bogaerts
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Three Dimensional ◽  
Threshold Concentration ◽  
Atmospheric Plasma ◽  
Current Standard ◽  
Cold Atmospheric Plasma ◽  
Anticancer Properties ◽  
Genetic Abnormalities ◽  
Dimensional Cell

Glioblastoma multiforme (GBM) is the most frequent and aggressive primary malignant brain tumor in adults. Current standard radiotherapy and adjuvant chemotherapy with the alkylating agent temozolomide (TMZ) yield poor clinical outcome. This is due to the stem-like properties of tumor cells and genetic abnormalities in GBM, which contribute to resistance to TMZ and progression. In this study, we used cold atmospheric plasma (CAP) to enhance the sensitivity to TMZ through inhibition of antioxidant signaling (linked to TMZ resistance). We demonstrate that CAP indeed enhances the cytotoxicity of TMZ by targeting the antioxidant specific glutathione (GSH)/glutathione peroxidase 4 (GPX4) signaling. We optimized the threshold concentration of TMZ on five different GBM cell lines (U251, LN18, LN229, U87-MG and T98G). We combined TMZ with CAP and tested it on both TMZ-sensitive (U251, LN18 and LN229) and TMZ-resistant (U87-MG and T98G) cell lines using two-dimensional cell cultures. Subsequently, we used a three-dimensional spheroid model for the U251 (TMZ-sensitive) and U87-MG and T98G (TMZ-resistant) cells. The sensitivity of TMZ was enhanced, i.e., higher cytotoxicity and spheroid shrinkage was obtained when TMZ and CAP were administered together. We attribute the anticancer properties to the release of intracellular reactive oxygen species, through inhibiting the GSH/GPX4 antioxidant machinery, which can lead to DNA damage. Overall, our findings suggest that the combination of CAP with TMZ is a promising combination therapy to enhance the efficacy of TMZ towards the treatment of GBM spheroids.

scholarly journals The synergistic effect of Canady Helios cold atmospheric plasma and a FOLFIRINOX regimen for the treatment of cholangiocarcinoma in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Olivia Jones ◽  
Xiaoqian Cheng ◽  
Saravana R. K. Murthy ◽  
Lawan Ly ◽  
Taisen Zhuang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Chemotherapy Regimen ◽  
Synergetic Effect ◽  
Atmospheric Plasma ◽  
High Recurrence Rate ◽  
Cold Atmospheric Plasma ◽  
Tract Cancer ◽  
Anticancer Properties ◽  
Potential Interactions

AbstractCholangiocarcinoma (CCA) is a rare biliary tract cancer with a low five-year survival rate and high recurrence rate after surgical resection. Currently treatment approaches include systemic chemotherapeutics such as FOLFIRINOX, a chemotherapy regimen is a possible treatment for severe CCA cases. A limitation of this chemotherapy regimen is its toxicity to patients and adverse events. There exists a need for therapies to alleviate the toxicity of a FOLFIRINOX regimen while enhancing or not altering its anticancer properties. Cold atmospheric plasma (CAP) is a technology with a promising future as a selective cancer treatment. It is critical to know the potential interactions between CAP and adjuvant chemotherapeutics. In this study the aim is to characterize the efficacy of FOLFIRINOX and CAP in combination to understand potential synergetic effect on CCA cells. FOLFIRINOX treatment alone at the highest dose tested (53.8 µM fluorouracil, 13.7 µM Leucovorin, 5.1 µM Irinotecan, and 3.7 µM Oxaliplatin) reduced CCA cell viability to below 20% while CAP treatment alone for 7 min reduced viability to 3% (p < 0.05). An analysis of cell viability, proliferation, and cell cycle demonstrated that CAP in combination with FOLFIRINOX is more effective than either treatment alone at a lower FOLFIRINOX dose of 6.7 µM fluorouracil, 1.7 µM leucovorin, 0.6 µM irinotecan, and 0.5 µM oxaliplatin and a shorter CAP treatment of 1, 3, or 5 min. In conclusion, CAP has the potential to reduce the toxicity burden of FOLFIRINOX and warrants further investigation as an adjuvant therapy.

scholarly journals Cold Atmospheric Plasma Treatment of Chondrosarcoma Cells Affects Proliferation and Cell Membrane Permeability

2020 ◽  
Vol 21 (7) ◽  
pp. 2291
Author(s):  
Lyubomir Haralambiev ◽  
Andreas Nitsch ◽  
Josephine M. Jacoby ◽  
Silas Strakeljahn ◽  
Sander Bekeschus ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Membrane Permeability ◽  
Surgical Resection ◽  
Cell Lines ◽  
Atp Release ◽  
Cell Types ◽  
Atmospheric Plasma ◽  
Cell Membrane Permeability ◽  
Membrane Function ◽  
Cold Atmospheric Plasma

Chondrosarcoma is the second most common malign bone tumor in adults. Surgical resection of the tumor is recommended because of its resistance to clinical treatment such as chemotherapy and radiation therapy. Thus, the prognosis for patients mainly depends on sufficient surgical resection. Due to this, research on alternative therapies is needed. Cold atmospheric plasma (CAP) is an ionized gas that contains various reactive species. Previous studies have shown an anti-oncogenic potential of CAP on different cancer cell types. The current study examined the effects of treatment with CAP on two chondrosarcoma cell lines (CAL-78, SW1353). Through proliferation assay, the cell growth after CAP-treatment was determined. A strong antiproliferative effect for both cell lines was detected. By fluorescein diacetate (FDA) assay and ATP release assay, alterations in the cell membrane and associated translocation of low molecular weight particles through the cytoplasmic membrane were observed. In supernatant, the non-membrane-permeable FDA and endogenously synthesized ATP detected suggest an increased membrane permeability after CAP treatment. Similar results were shown by the dextran-uptake assay. Furthermore, fluorescence microscopic G-/F-actin assay was performed. G- and F-actin were selectively dyed, and the ratio was measured. The presented results indicate CAP-induced changes in cell membrane function and possible alterations in actin-cytoskeleton, which may contribute to the antiproliferative effects of CAP.

scholarly journals Scorpion Venom Causes Upregulation of p53 and Downregulation of Bcl-xL and BID Protein Expression by Modulating Signaling Proteins Erk1/2 and STAT3, and DNA Damage in Breast and Colorectal Cancer Cell Lines

2017 ◽  
Vol 17 (2) ◽  
pp. 271-281 ◽  
Author(s):  
Abdulrahman Khazim Al-Asmari ◽  
Anvarbatcha Riyasdeen ◽  
Mozaffarul Islam
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Anticancer Agent ◽  
Cancer Cell Lines ◽  
Scorpion Venom ◽  
Breast Cancer Cell Lines ◽  
Anticancer Properties

Scorpion venoms efficiently block the normal neurotransmitter signaling pathway by prejudicing the ion channel operating mechanism in the body system. Besides its negative effect, venoms also possess some beneficial qualities for humans. They have also been shown to exhibit anticancer properties in various cancer types. This unique property of the venom as an anticancer agent is mainly a result of its role in initiating apoptosis and inhibiting several signaling cascade mechanisms that promote cancer cell proliferation and growth. In this study, we examine the effect of venom on phenotypic changes as well as changes at the molecular levels in colorectal and breast cancer cell lines. A dramatic decrease in cell invasion was observed in both cancer cell lines on venom treatment. Additionally, there was decrease in IL-6, RhoC, Erk1/2, and STAT3 in venom-treated cell lines, providing strong evidence of its anticancer properties. Furthermore, decrease in the expression of antiapoptotic proteins and also upregulation of proapoptotic ones by these lines were observed on venom treatment. Moreover, a vivid picture of DNA damage was also detected on venom treatment. In conclusion, scorpion venom possesses significant potential as an anticancer agent against colorectal and breast cancer cell lines.

Assessment of Mutations Induced by Cold Atmospheric Plasma Jet Treatment Relative to Known Mutagens in Escherichia coli

Mutagenesis ◽  
2021 ◽  
Author(s):  
Bethany L Patenall ◽  
Hollie J Hathaway ◽  
Maisem Laabei ◽  
Amber E Young ◽  
Naing T Thet ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Dna Fragmentation ◽  
Ames Test ◽  
Plasma Jet ◽  
Atmospheric Plasma ◽  
Nitrogen Species ◽  
Cold Atmospheric Plasma ◽  
X Irradiation ◽  
Mutagenic Effects

Abstract The main bactericidal components of cold atmospheric plasma (CAP) are thought to be reactive oxygen and nitrogen species (RONS) and UV radiation, both of which have the capacity to cause DNA damage and mutations. Here, the mutagenic effects of CAP on Escherichia coli were assessed in comparison to X- and UV-irradiation. DNA damage and mutagenesis were screened for using a diffusion-based DNA fragmentation assay and modified Ames test respectively. Mutant colonies obtained from the latter were quantitated and sequenced. CAP was found to elicit a similar mutation spectrum to X-irradiation, that did not resemble that for UV implying that CAP produced RONS are more likely the mutagenic component of CAP. CAP treatment was also shown to promote resistance to the antibiotic ciprofloxacin. Our data suggest that CAP treatment has mutagenic effects that may have important phenotypic consequences.

Anticancer Properties of a New Hybrid Analog AD-013 Combining a Coumarin Scaffold with an α-methylene-δ-lactone Motif

2018 ◽  
Vol 18 (3) ◽  
pp. 450-457 ◽  
Author(s):  
Angelika Dlugosz ◽  
Katarzyna Gach-Janczak ◽  
Jacek Szymanski ◽  
Dariusz Deredas ◽  
Henryk Krawczyk ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Pcr Analysis ◽  
Cytotoxic Activities ◽  
Anticancer Properties ◽  
Apoptotic Genes ◽  
Mcf 7

Background: Coumarin is a natural phytochemical but as such has no medical uses. However, various natural and synthetic coumarin analogs attract attention due to their interesting biological properties. Objective: Here, we evaluated and compared anticancer properties of a new synthetic hybrid compound AD- 013, which integrates a coumarin moiety and an α-methylene-δ-lactone motif, with novobiocin, a natural antibiotic bearing a coumarin scaffold. Methods: Cytotoxic activities of compound AD-013 and novobiocin were assessed by the MTT assay. In order to explore the mechanism of anticancer activity of analog AD-013, we performed quantitative real-time PCR analysis of apoptosis- and cell cycle-related genes. The ability of AD-013 and novobiocin to induce apoptosis and DNA damage was studied by flow cytometry. Results: The cytotoxic activity of this new compound was compared with the activity of a coumarin-based antibiotic novobiocin against two cancer cell lines, MCF-7 and HL-60 and also against normal human cells, MCF- 10A and HUVEC. AD-013 was much more cytotoxic than novobiocin in both cancer cell lines and showed some selectivity against MCF-7 cancer cells as compared with MCF-10A healthy cells. Expression levels of the pro-apoptotic genes significantly increased while the anti-apoptotic genes, were down-regulated for both compounds in both cancer cell lines. </P><P> AD-013 was able to inhibit cell proliferation, generate DNA damage and induce apoptosis. The obtained data showed that this compound caused the cell cycle arrest in subG0/G1 in both cancer cell lines. Conclusion: The new hybrid analog was a much stronger apoptosis inducer than novobiocin and activated the intrinsic pathway of apoptosis.

scholarly journals Reduction of Human Glioblastoma Spheroids Using Cold Atmospheric Plasma: The Combined Effect of Short- and Long-Lived Reactive Species

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 394 ◽  
Author(s):  
Angela Privat-Maldonado ◽  
Yury Gorbanev ◽  
Sylvia Dewilde ◽  
Evelien Smits ◽  
Annemie Bogaerts
Keyword(s):  
Cell Migration ◽  
Tumour Size ◽  
Three Dimensional ◽  
Tumour Microenvironment ◽  
Atmospheric Plasma ◽  
Paramagnetic Resonance ◽  
Cold Atmospheric Plasma ◽  
And Control ◽  
Phosphate Buffered Saline

Cold atmospheric plasma (CAP) is a promising technology against multiple types of cancer. However, the current findings on the effect of CAP on two-dimensional glioblastoma cultures do not consider the role of the tumour microenvironment. The aim of this study was to determine the ability of CAP to reduce and control glioblastoma spheroid tumours in vitro. Three-dimensional glioblastoma spheroid tumours (U87-Red, U251-Red) were consecutively treated directly and indirectly with a CAP using dry He, He + 5% H2O or He + 20% H2O. The cytotoxicity and spheroid shrinkage were monitored using live imaging. The reactive oxygen and nitrogen species produced in phosphate buffered saline (PBS) were measured by electron paramagnetic resonance (EPR) and colourimetry. Cell migration was also assessed. Our results demonstrate that consecutive CAP treatments (He + 20% H2O) substantially shrank U87-Red spheroids and to a lesser degree, U251-Red spheroids. The cytotoxic effect was due to the short- and long-lived species delivered by CAP: they inhibited spheroid growth, reduced cell migration and decreased proliferation in CAP-treated spheroids. Direct treatments were more effective than indirect treatments, suggesting the importance of CAP-generated, short-lived species for the growth inhibition and cell cytotoxicity of solid glioblastoma tumours. We concluded that CAP treatment can effectively reduce glioblastoma tumour size and restrict cell migration, thus demonstrating the potential of CAP therapies for glioblastoma.

scholarly journals Interaction of cold atmospheric plasma jet with bio targets: different sensitivities of human cell lines

2019 ◽  
Vol 1393 ◽  
pp. 012153
Author(s):  
Dm Zakrevsky ◽  
E Yelak ◽  
P Gugin ◽  
E Golubitskaya ◽  
O Troizkaja ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cell ◽  
Plasma Jet ◽  
Atmospheric Plasma ◽  
Human Cell Lines ◽  
Cold Atmospheric Plasma

scholarly journals Cold Atmospheric Plasma, a Novel Approach against Bladder Cancer, with Higher Sensitivity for the High-Grade Cell Line

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 41
Author(s):  
Edgar Tavares-da-Silva ◽  
Eurico Pereira ◽  
Ana S. Pires ◽  
Ana R. Neves ◽  
Catarina Braz-Guilherme ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cell Viability ◽  
Cell Line ◽  
Cell Lines ◽  
Metabolic Activity ◽  
Atmospheric Plasma ◽  
High Grade ◽  
Cold Atmospheric Plasma ◽  
Higher Sensitivity

Antitumor therapies based on Cold Atmospheric Plasma (CAP) are an emerging medical field. In this work, we evaluated CAP effects on bladder cancer. Two bladder cancer cell lines were used, HT-1376 (stage III) and TCCSUP (stage IV). Cell proliferation assays were performed evaluating metabolic activity (MTT assay) and protein content (SRB assay). Cell viability, cell cycle, and mitochondrial membrane potential (Δψm) were assessed using flow cytometry. Reactive oxygen and nitrogen species (RONS) and reduced glutathione (GSH) were evaluated by fluorescence. The assays were carried out with different CAP exposure times. For both cell lines, we obtained a significant reduction in metabolic activity and protein content. There was a decrease in cell viability, as well as a cell cycle arrest in S phase. The Δψm was significantly reduced. There was an increase in superoxide and nitric oxide and a decrease in peroxide contents, while GSH content did not change. These results were dependent on the exposure time, with small differences for both cell lines, but overall, they were more pronounced in the TCCSUP cell line. CAP showed to have a promising antitumor effect on bladder cancer, with higher sensitivity for the high-grade cell line.

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