scholarly journals MCF-7 and its Multidrug Resistant Variant MCF-7/ADR Overcome TNF Cytotoxicity through Prevention of Reactive Oxygen Species Accumulation

2019 ◽  
Vol 25 (2) ◽  
pp. 118-123
Author(s):  
Morteza Ghandadi ◽  
Javad Behravan ◽  
Samira Biabani ◽  
Sara Abbaspor ◽  
Fatemeh Mosaffa
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Multidrug Resistant ◽  
Oxygen Species ◽  
Resistant Variant ◽  
Ros Accumulation ◽  
Tnf Α ◽  
Factor Α ◽  
Mcf 7

Background: Signal transduction of numerous cytokines and growth factors are mediated by reactive oxygen species (ROS). Tumor necrosis factor-α (TNF-α) have stimulated accumulation of ROS in various in vitro studies. MCF-7 and its Adriamycin resistant variant MCF-7/ADR are resistant against TNF-α cytotoxicity. Role of ROS in the resistance of MCF-7 and MCF-7/ADR cells was investigated. Methods: ROS accumulation and viability in MCF-7 and MCF-7/ADR after TNF-α exposure was evaluated using 2',7'-dichlorofluorescein diacetate (DCFH-DA) as a fluorescent probe and 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide (MTT) cytotoxicity assay respectively. Results: ROS level did not change significantly after TNF-α exposure. Induction of ROS accumulation along with TNF-α treatment sensitized these cells to TNF-α toxicity. Conclusion: It can be concluded that lack of ROS accumulation following TNF-α exposure is involved at least by part in the resistance of MCF-7 and its drug resistant derivative MCF-7/ADR cells to TNF-α cytotoxicity.

scholarly journals Salvianolic Acid A Protects Against Oxidative Stress and Apoptosis Induced by Intestinal Ischemia-Reperfusion Injury Through Activation of Nrf2/HO-1 Pathways

2018 ◽  
Vol 49 (6) ◽  
pp. 2320-2332 ◽  
Author(s):  
Guo Zu ◽  
Tingting Zhou ◽  
Ningwei Che ◽  
Xiangwen Zhang
Keyword(s):  
Reactive Oxygen Species ◽  
Glutathione Peroxidase ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Tnf Α

Background/Aims: Ischemia-reperfusion (I/R) adversely affects the intestinal mucosa. The major mechanisms of I/R are the generation of reactive oxygen species (ROS) and apoptosis. Salvianolic acid A (SalA) is suggested to be an effective antioxidative and antiapoptotic agent in numerous pathological injuries. The present study investigated the protective role of SalA in I/R of the intestine. Methods: Adult male Sprague-Dawley rats were subjected to intestinal I/R injury in vivo. In vitro experiments were performed in IEC-6 cells subjected to hypoxia/ reoxygenation (H/R) stimulation to simulate intestinal I/R. TNF-α, IL-1β, and IL-6 levels were measured using enzyme-linked immunosorbent assay. Malondialdehyde and myeloperoxidase and glutathione peroxidase levels were measured using biochemical analysis. Apoptosis was measured by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling staining or flow cytometry in vivo and in vitro. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. Western blotting was performed to determine the expression of heme oxygenase-1 (HO-1), Nrf2 and proteins associated with apoptosis. The mRNA expressions of Nrf2 and HO-1 were detected by quantitative real-time polymerase chain reaction in vivo and in vitro. Results: Malondialdehyde level and myeloperoxidase and glutathione peroxidase, TNF-α, IL-1β, and IL-6 levels group in intestinal tissue decreased significantly in the SalA pretreatment groups compared to the I/R group. SalA markedly abolished intestinal injury compared to the I/R group. SalA significantly attenuated apoptosis and increased Nrf2/HO-1 expression in vivo and in vitro. However, Nrf2 siRNA treatment partially abrogated the above mentioned effects of SalA in H/R-induced ROS and apoptosis in IEC-6 cells. Conclusion: The present study demonstrated that SalA ameliorated oxidation, inhibited the release of pro-inflammatory cytokines and alleviated apoptosis in I/R-induced injury and that these protective effects may partially occur via regulation of the Nrf2/ HO-1 pathways.

scholarly journals Multidrug-resistant Acinetobacter baumannii resists reactive oxygen species and survives in macrophages

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yoshinori Sato ◽  
Yuka Unno ◽  
Chizuru Miyazaki ◽  
Tsuneyuki Ubagai ◽  
Yasuo Ono
Keyword(s):  
Reactive Oxygen Species ◽  
Acinetobacter Baumannii ◽  
Reactive Oxygen ◽  
Bacterial Count ◽  
Multidrug Resistant ◽  
Intracellular Reactive Oxygen Species ◽  
Clinical Isolates ◽  
Oxygen Species ◽  
Tnf Α ◽  
Mouse Macrophages

AbstractWe investigated the intracellular survival of multidrug-resistant Acinetobacter baumannii (MDRAB) clinical isolates in macrophages, after phagocytosis, to determine their virulence characteristics. After ATCC 19606 and 5 clinical isolates of MDRAB were phagocytosed by mouse and human macrophages, the bacterial count of MDRAB strains, R4 and R5, increased in the mouse macrophages, 24 hours after phagocytosis. Bacterial count of the strains, R1 and R2, was almost equal 4 and 24 hours after phagocytosis. Intracellular reactive oxygen species was detected in the macrophages after phagocytosis of these bacteria. Further, the strains R1, R2, R4, and R5 showed higher catalase activity than ATCC 19606. Additionally, strains R1, R4, and R5 grew more efficiently than ATCC 19606 in the presence of H2O2, whereas growth of strains R2 and R3 was marginally more than that of ATCC 19606 in the presence of H2O2. The MDRAB clinical isolates altered the expression of TNF-α, IL-1β, IL-6, and MIP-2 mRNA induced in J774A.1 cells, 24 hours after phagocytosis. These results provide insights into the renewed virulence characteristics of MDRAB clinical isolates. Finally, tigecycline killed MDRAB phagocytosed by the macrophages more effectively than colistin, although colistin and tigecycline are both considered effective antibiotics for the treatment of MDRAB.

scholarly journals Sulphamoylated Estradiol Analogue Induces Reactive Oxygen Species Generation to Exert Its Antiproliferative Activity in Breast Cancer Cell Lines

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4337
Author(s):  
Maphuti T. Lebelo ◽  
Anna M. Joubert ◽  
Michelle H. Visagie
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Superoxide Anion ◽  
Fluorescent Microscopy ◽  
Reactive Oxygen ◽  
Breast Cancer Cell Lines ◽  
Oxygen Species ◽  
Morphological Studies ◽  
Mcf 7

2-Methoxyestradiol (2ME), a 17β-estradiol metabolite, exerts anticancer properties in vitro and in vivo. To address 2ME’s low bioavailability, research led to the in silico design of sulphamoylated 2ME analogues. However, the role of oxidative stress induced in the activity exerted by sulphamoylated compounds remains elusive. In the current study, the influence of 2-Ethyl-17-oxoestra-1,3,5(10)-trien-3-yl sulphamate (ESE-one) on reactive oxygen species (ROS) induction and its effect on cell proliferation, as well as morphology, were assessed in breast tumorigenic cells (MCF-7 and MDA-MB-231). Fluorescent microscopy showed that sulphamoylated estradiol analogues induced hydrogen peroxide and superoxide anion, correlating with decreased cell growth demonstrated by spectrophotometry data. ESE-one exposure resulted in antiproliferation which was repressed by tiron (superoxide inhibitor), trolox (peroxyl inhibitor) and N,N′-dimethylthiourea (DMTU) (hydrogen peroxide inhibitor). Morphological studies demonstrated that tiron, trolox and DMTU significantly decreased the number of rounded cells and shrunken cells in MCF-7 and MDA-MB-231 cells induced by ESE-one. This in vitro study suggests that ESE-one induces growth inhibition and cell rounding by production of superoxide anion, peroxyl radical and hydrogen peroxide. Identification of these biological changes in cancer cells caused by sulphamoylated compounds hugely contributes towards improvement of anticancer strategies and the ROS-dependent cell death pathways in tumorigenic breast cells.

scholarly journals Metabolism of Reactive Oxygen Species in Osteosarcoma and Potential Treatment Applications

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 87 ◽  
Author(s):  
Wei Sun ◽  
Bing Wang ◽  
Xing-Long Qu ◽  
Bi-Qiang Zheng ◽  
Wen-Ding Huang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Tumour Growth ◽  
Xenograft Model ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mg63 Cells ◽  
Ros Accumulation ◽  
Ros Formation

Background: The present study was designed to explore the underlying role of hypoxia-inducible factor 1α (HIF-1α) in reactive oxygen species (ROS) formation and apoptosis in osteosarcoma (OS) cells induced by hypoxia. Methods: In OS cells, ROS accumulated and apoptosis increased within 24 h after exposure to low HIF-1α expression levels. A co-expression analysis showed that HIF was positively correlated with Forkhead box class O1 (FoxO1) expression and negatively correlated with CYP-related genes from the National Center for Biotechnology Information’s Gene Expression Omnibus (NCBI GEO) datasets. Hypoxia also considerably increased HIF-1α and FoxO1 expression. Moreover, the promoter region of FoxO1 was directly regulated by HIF-1α. We inhibited HIF-1α via siRNA and found that the ROS accumulation and apoptosis induced by hypoxia in OS cells decreased. In this study, a murine xenograft model of BALB-c nude mice was adopted to test tumour growth and measure the efficacy of 2-ME + As2O3 treatment. Results: Ad interim knockdown of HIF-1α also inhibited manganese-dependent superoxide dismutase (MnSOD), catalase and sestrin 3 (Sesn3) expression in OS cells. Furthermore, hypoxia-induced ROS formation and apoptosis in OS cells were associated with CYP450 protein interference and were ablated by HIF-1α silencing via siRNA. Conclusions: Our data reveal that HIF-1α inhibits ROS accumulation by directly regulating FoxO1 in OS cells, which induces MnSOD, catalase and Sesn3 interference, thus resulting in anti-oxidation effects. The combination of an HIF-1α inhibitor (2-mercaptoethanol,2-ME) and ROS inducer (arsenous oxide, As2O3) can prohibit proliferation and migration and promote apoptosis in MG63 cells in vitro while inhibiting tumour growth in vivo.

scholarly journals Quinazolin-derived myeloperoxidase inhibitor suppresses influenza A virus-induced reactive oxygen species, pro-inflammatory mediators and improves cell survival

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254632
Author(s):  
Juan A. De La Cruz ◽  
Thota Ganesh ◽  
Becky A. Diebold ◽  
Weiping Cao ◽  
Amelia Hofstetter ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Influenza A Virus ◽  
Inflammatory Mediators ◽  
Influenza A ◽  
Mononuclear Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α

Superoxide radicals and other reactive oxygen species (ROS) are implicated in influenza A virus-induced inflammation. In this in vitro study, we evaluated the effects of TG6-44, a novel quinazolin-derived myeloperoxidase-specific ROS inhibitor, on influenza A virus (A/X31) infection using THP-1 lung monocytic cells and freshly isolated peripheral blood mononuclear cells (PBMC). TG6-44 significantly decreased A/X31-induced ROS and virus-induced inflammatory mediators in THP-1 cells (IL-6, IFN-γ, MCP-1, TNF-α, MIP-1β) and in human PBMC (IL-6, IL-8, TNF-α, MCP-1). Interestingly, TG6-44-treated THP-1 cells showed a decrease in percent cells expressing viral nucleoprotein, as well as a delay in translocation of viral nucleoprotein into the nucleus. Furthermore, in influenza A virus-infected cells, TG6-44 treatment led to suppression of virus-induced cell death as evidenced by decreased caspase-3 activation, decreased proportion of Annexin V+PI+ cells, and increased Bcl-2 phosphorylation. Taken together, our results demonstrate the anti-inflammatory and anti-infective effects of TG6-44.

scholarly journals Cytotoxic Effect of Curcumin on Malaria Parasite Plasmodium falciparum: Inhibition of Histone Acetylation and Generation of Reactive Oxygen Species

2006 ◽  
Vol 51 (2) ◽  
pp. 488-494 ◽  
Author(s):  
Long Cui ◽  
Jun Miao ◽  
Liwang Cui
Keyword(s):  
Reactive Oxygen Species ◽  
Plasmodium Falciparum ◽  
Cytotoxic Effect ◽  
Nuclear Dna ◽  
Reactive Oxygen ◽  
Multidrug Resistant ◽  
Oxygen Species ◽  
Mammalian Cell Lines ◽  
Parasite Plasmodium Falciparum

ABSTRACT The emergence of multidrug-resistant parasites is a major concern for malaria control, and development of novel drugs is a high priority. Curcumin, a natural polyphenolic compound, possesses diverse pharmacological properties. Among its antiprotozoan activities, curcumin was potent against both chloroquine-sensitive and -resistant Plasmodium falciparum strains. Consistent with findings in mammalian cell lines, curcumin's prooxidant activity promoted the production in P. falciparum of reactive oxygen species (ROS), whose cytotoxic effect could be antagonized by coincubation with antioxidants and ROS scavengers. Curcumin treatment also resulted in damage of both mitochondrial and nuclear DNA, probably due to the elevation of intracellular ROS. Furthermore, we have demonstrated that curcumin inhibited the histone acetyltransferase (HAT) activity of the recombinant P. falciparum general control nonderepressed 5 (PfGCN5) in vitro and reduced nuclear HAT activity of the parasite in culture. Curcumin-induced hypoacetylation of histone H3 at K9 and K14, but not H4 at K5, K8, K12, and K16, suggested that curcumin caused specific inhibition of the PfGCN5 HAT. Taken together, these results indicated that at least the generation of ROS and down-regulation of PfGCN5 HAT activity accounted for curcumin's cytotoxicity for malaria parasites.

scholarly journals Sevoflurane modulates the release of reactive oxygen species, myeloperoxidase, and elastase in human whole blood: Effects of different stimuli on neutrophil response to volatile anesthetic in vitro

2017 ◽  
Vol 30 (4) ◽  
pp. 362-370
Author(s):  
Grégory Minguet ◽  
Thierry Franck ◽  
Jean Joris ◽  
Didier Serteyn
Keyword(s):  
Reactive Oxygen Species ◽  
Whole Blood ◽  
Reactive Oxygen ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Polymorphonuclear Neutrophil ◽  
Oxygen Species ◽  
Tnf Α ◽  
Stimulation Of

Volatile anesthetics have been shown to modulate polymorphonuclear neutrophil (PMN) functions. The aim of this study was to examine the impact of clinically relevant concentrations of sevoflurane (SEVO), a volatile anesthetic, on the release of reactive oxygen species (ROS), myeloperoxidase (MPO), and elastase (EL) from human activated PMNs. For this purpose, samples of whole blood were collected from healthy volunteers and exposed in vitro to 2.3% or 4.6% SEVO in air. To assess for a stimulus-dependent effect of the volatile anesthetic, PMNs were activated using different validated protocols. Artificial stimulation of neutrophils involved either a combination of cytochalasin B (CB) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA). In addition, a combination of lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-α) was also tested as a natural activation mean of PMNs. The production of ROS by PMNs was assessed by L-012 chemiluminescence. Total MPO and EL released in supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Furthermore, degranulation of the active fraction of MPO was also measured by specific immunological extraction followed by enzymatic detection (SIEFED). Overall, SEVO enhanced the release of ROS, MPO, and EL following artificial stimulation of PMNs but the volatile anesthetic inhibited the degranulation of active MPO and EL after neutrophil exposure to LPS and TNF-α. This study highlighted that the effect of SEVO on activated PMNs is dependent on the conditions of cell stimulation. These properties should be taken into consideration in future studies investigating immunomodulatory effects of volatile anesthetics.

scholarly journals Modulation of reactive oxygen species by Rac1 or catalase prevents asbestos-induced pulmonary fibrosis

2009 ◽  
Vol 297 (5) ◽  
pp. L846-L855 ◽  
Author(s):  
Shubha Murthy ◽  
Andrea Adamcakova-Dodd ◽  
Sarah S. Perry ◽  
Linda A. Tephly ◽  
Richard M. Keller ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Fibrosis ◽  
Alveolar Macrophages ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Tnf Α

The release of reactive oxygen species (ROS) and cytokines by alveolar macrophages has been demonstrated in asbestos-induced pulmonary fibrosis, but the mechanism linking alveolar macrophages to the pathogenesis is not known. The GTPase Rac1 is a second messenger that plays an important role in host defense. In this study, we demonstrate that Rac1 null mice are protected from asbestos-induced pulmonary fibrosis, as determined by histological and biochemical analysis. We hypothesized that Rac1 induced pulmonary fibrosis via generation of ROS. Asbestos increased TNF-α and ROS in a Rac1-dependent manner. TNF-α was elevated only 1 day after exposure, whereas ROS generation progressively increased in bronchoalveolar lavage cells obtained from wild-type (WT) mice. To determine whether ROS generation contributed to pulmonary fibrosis, we overexpressed catalase in WT monocytes and observed a decrease in ROS generation in vitro . More importantly, administration of catalase to WT mice attenuated the development of fibrosis in vivo. For the first time, these results demonstrate that Rac1 plays a crucial role in asbestos-induced pulmonary fibrosis. Moreover, it suggests that a simple intervention may be useful to prevent progression of the disease.

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