Extracellular superoxide dismutase and its role in cancer

Griess, Brandon; Tom, Eric; Domann, Frederick E.; Teoh-Fitzgerald, Melissa

doi:10.1016/j.freeradbiomed.2017.08.013

Cited by 145 publications

(131 citation statements)

References 229 publications

(271 reference statements)

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“…SOD is a type of primary cellular antioxidant catalyzing the conversion of superoxide to H 2 O 2 , which has been proven to favor tumor progression (12). There are three members of the SOD family present in mammals, namely CuZnSOD, MnSOD and extracellular SOD (EC-SOD), which are located in different places inside or outside the cell (28). Epidemiological evidence has indicated that increased levels of SOD were observed in several tumor types along with tumor progression from early-stage (non-invasive) to late-stage (metastatic) (29).…”

Section: Discussionmentioning

confidence: 99%

Curcumin inhibits superoxide dismutase-induced epithelial-to-mesenchymal transition via the PI3K/Akt/NF-κB pathway in pancreatic cancer cells

Jiang

Xiao

et al. 2018

Int J Oncol

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Curcumin is a natural polyphenol compound derived from turmeric. It possesses multiple pharmacological properties, including antioxidant, anti-inﬂammatory and anti-tumor progression properties. Our recent study demonstrated that superoxide dismutase (SOD)-dependent production of hydrogen peroxide (H2O2) promoted the invasive and migratory activity of pancreatic cancer cells. However, whether curcumin suppresses SOD-induced cancer progression and the related mechanisms remains unclear. Since epithelial‑to-mesenchymal transition (EMT) plays a key role in tumor metastasis, the aim of the present study was to examine whether curcumin intervenes with SOD-induced EMT in pancreatic cancer and the underlying mechanism. The human pancreatic cancer cells BxPC-3 and Panc-1 were exposed to SOD in the presence or absence of curcumin, catalase (CAT, a scavenger of H2O2), or LY 294002 [a phosphoinositide-3 kinase (PI3K) inhibitor]. Intracellular reactive oxygen species (ROS) and H2O2 were evaluated by 2,7-dichlorodihydroﬂuorecein diacetate and H2O2 assay, respectively. The activation of p-Akt and p-nuclear factor (NF)-κB were examined by western blotting. The migratory and invasive abilities of pancreatic cancer cells were tested by the wound healing and Transwell invasion assays. The expression of E-cadherin, N-cadherin and vimentin (EMT-related genes) were measured by reverse transcription-quantitative polymerase chain reaction and western blotting at the mRNA and protein levels, respectively. The findings of the present study demonstrated that curcumin decreased SOD-induced production of ROS and H2O2 in BxPC-3 and Panc-1 cells. Curcumin was able to suppress SOD-induced invasion and migration, and it also regulated the expression of the above‑mentioned EMT-related genes and cell morphology. SOD-induced cell invasion was also inhibited by catalase and LY 294002. Furthermore, the levels of p-Akt and p-NF-κB caused by SOD could be offset by treatment with curcumin and LY 294002. To summarize, these results demonstrated that curcumin was able to prevent SOD-driven H2O2-induced pancreatic cancer metastasis by blocking the PI3K/Akt/NF-κB signaling pathway. The use of curcumin to inhibit the H2O2/Akt/NF-κB axis may be a promising therapeutic approach to the treatment of patients with pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Curcumin inhibits superoxide dismutase-induced epithelial-to-mesenchymal transition via the PI3K/Akt/NF-κB pathway in pancreatic cancer cells

Jiang

Xiao

et al. 2018

Int J Oncol

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“…For example, tumors associated macrophages have been shown to induce sub-lethal oxidative stress in murine mammary cancer cells, maybe through the secretion of TNF-α. On the other hand, extracellular superoxide dismutases might finely tuning the levels of H 2 O 2 in the extracellular milieu altering the proliferation and differentiation of immune cells ( 200 ). In fact, ROS may induce decreased viability in CD4+ T lymphocytes and the inhibition of DNA synthesis ( 181 , 201 ).…”

Section: Redox Control Of Cellular Fatementioning

confidence: 99%

Influence of Inflammation in the Process of T Lymphocyte Differentiation: Proliferative, Metabolic, and Oxidative Changes

et al. 2018

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T lymphocytes, from their first encounter with their specific antigen as naïve cell until the last stages of their differentiation, in a replicative state of senescence, go through a series of phases. In several of these stages, T lymphocytes are subjected to exponential growth in successive encounters with the same antigen. This entire process occurs throughout the life of a human individual and, earlier, in patients with chronic infections/pathologies through inflammatory mediators, first acutely and later in a chronic form. This process plays a fundamental role in amplifying the activating signals on T lymphocytes and directing their clonal proliferation. The mechanisms that control cell growth are high levels of telomerase activity and maintenance of telomeric length that are far superior to other cell types, as well as metabolic adaptation and redox control. Large numbers of highly differentiated memory cells are accumulated in the immunological niches where they will contribute in a significant way to increase the levels of inflammatory mediators that will perpetuate the new state at the systemic level. These levels of inflammation greatly influence the process of T lymphocyte differentiation from naïve T lymphocyte, even before, until the arrival of exhaustion or cell death. The changes observed during lymphocyte differentiation are correlated with changes in cellular metabolism and these in turn are influenced by the inflammatory state of the environment where the cell is located. Reactive oxygen species (ROS) exert a dual action in the population of T lymphocytes. Exposure to high levels of ROS decreases the capacity of activation and T lymphocyte proliferation; however, intermediate levels of oxidation are necessary for the lymphocyte activation, differentiation, and effector functions. In conclusion, we can affirm that the inflammatory levels in the environment greatly influence the differentiation and activity of T lymphocyte populations. However, little is known about the mechanisms involved in these processes. The elucidation of these mechanisms would be of great help in the advance of improvements in pathologies with a large inflammatory base such as rheumatoid arthritis, intestinal inflammatory diseases, several infectious diseases and even, cancerous processes.

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“…Superoxide radical is produced by the single electron reduction of the oxygen molecule. This reactive free radical is rapidly converted to hydrogen peroxide via superoxide dismutase (SOD), which is the only enzyme that scavenges superoxide [5]. Hydrogen peroxide is also a highly reactive molecule that is broken down into water by 2 types of enzymes, catalase (CAT) and glutathione peroxidase (GPx).…”

Section: Introductionmentioning

confidence: 99%

Glutathione level and glutathione reductase activity in serum of coronary heart disease patients

Zuzak¹,

Horecka²,

Kiełczykowska³

et al. 2017

J Pre Clin Clin Res.

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level and glutathione reductase activity in serum of coronary heart disease patients. J Pre-Clin Clin Res. 2017; 11(2): 103-105. doi: 10.26444/jpccr/81277 Abstract Introduction. Oxidative stress induced by the generation of excess reactive oxygen species is one of the cause of atherosclerosis finally leading to coronary heart disease (CHD). Glutathione reductase (GR), a flavoprotein antioxidant enzyme, regenerates glutathione (GSH) from its oxidized form, which is essential for scavenging of hydrogen peroxide by glutathione peroxidase. The aim of this study was to analyze the activity of GR and GSH level in serum of patients with various stages of CHD. Materials and method. Sixty consecutive patients with diagnosis of stable angina (SA, n=20), unstable angina (UA, n=20) and non-fatal myocardial infarction (MI, n=20) together with 20 healthy control subjects were enrolled. Venous blood samples were collected just before the coronary catheterization procedure (in study patients). GR activities and GSH concentration was determined using commercially available colorimetric kits. Results. The highest GR activity and GSH serum level was noticed in UA patients. However, statistical evaluation showed that only glutathione reductase activity was significantly higher in serum obtained from myocardial infarction patients, compared to stable angina pectoris patients (19.52 ± 13.88 vs 11.63 ± 5.45 nmol/min/ml for MI and SA, respectively; p<0.048). There were no significant differences in GSH between the CHD patients and controls. Conclusion. The elevated activity of glutathione reductase in serum of patients with unstable angina pectoris and myocardial infarction suggests the role of antioxidant system acute coronary syndromes.

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Extracellular superoxide dismutase and its role in cancer

Cited by 145 publications

References 229 publications

Curcumin inhibits superoxide dismutase-induced epithelial-to-mesenchymal transition via the PI3K/Akt/NF-κB pathway in pancreatic cancer cells

Curcumin inhibits superoxide dismutase-induced epithelial-to-mesenchymal transition via the PI3K/Akt/NF-κB pathway in pancreatic cancer cells

Influence of Inflammation in the Process of T Lymphocyte Differentiation: Proliferative, Metabolic, and Oxidative Changes

Glutathione level and glutathione reductase activity in serum of coronary heart disease patients

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