Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate the alterations in lipid peroxidation and antioxidant enzyme defences in the blood of patients with malignant breast tumour and benign breast disease. Forty patients with malignant breast tumour, 20 patients with benign breast disease and also 20 healthy control subjects were recruited for the study. Malondialdehyde levels in plasma and erythrocytes, and the activities of erythrocyte CuZn-superoxide dismutase, catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase were measured. Malondialdehyde levels were higher in patients with both benign breast disease and malignant breast tumour compared with control subjects. The activities of all antioxidant enzymes were higher in patients with malignant breast tumour, while only glutathione peroxidase and CuZn-superoxide dismutase activities were higher in patients with benign breast disease. Except for glucose-6-phosphate dehydrogenase, the antioxidant enzymes studied correlated positively with the malondialdehyde levels in patients with malignant breast tumour. On the other hand, only glucose-6-phosphate dehydrogenase activity was increased by the level of malignancy. The activity increases in erythrocyte antioxidant enzymes may be a compensatory upregulation in response to increased oxidative stress especially in patients with malignant breast tumour.
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PMID:Oxidant/antioxidant status in blood of patients with malignant breast tumour and benign breast disease. 1241 67

The trace mineral selenium inhibits cancer development in a variety of experimental animal models. We used an in vivo canine model to evaluate the effects of dietary selenium supplementation on DNA damage in prostate tissue and on apoptosis in prostate epithelial cells. Sexually intact elderly male beagle dogs were randomly assigned to receive an unsupplemented diet (control group) or diets that were supplemented with selenium (treatment group), either as selenomethionine or as high-selenium yeast at 3 micro g/kg or 6 micro g/kg body weight per day for 7 months. The extent of DNA damage in prostate cells and in peripheral blood lymphocytes, as determined by the alkaline comet assay, was lower among the selenium-supplemented dogs than among the control dogs (prostate P<.001; peripheral blood lymphocytes P =.003; analysis of variance) but was not associated with the activity of the antioxidant enzyme glutathione peroxidase in plasma. The median number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive (i.e., apoptotic) prostate epithelial cells was 3.7 (interquartile range = 1.1-7.6) for the selenium-supplemented dogs and 1.7 (interquartile range = 0.2-2.8) for the control dogs ( P =.04, Mann-Whitney U test). These data suggest that dietary selenium supplementation decreases DNA damage and increases epithelial cell apoptosis within the aging canine prostate.
J Natl Cancer Inst 2003 Feb 05
PMID:Effects of dietary selenium supplementation on DNA damage and apoptosis in canine prostate. 1256 46

The stratum corneum, as the body's principal barrier to the environment, is continuously exposed to environmental sources of reactive oxygen species like ultraviolet light, ozone, and pollution. Reactive oxygen species are believed to be involved in cancer, aging, and inflammatory skin disorders. We have developed a method to measure catalase and superoxide dismutase activity on tape strippings from the human stratum corneum and demonstrated a gradient of antioxidant enzyme activity across the stratum corneum with decreasing levels towards the skin surface. Sun exposure resulted in a seasonal variation of the catalase activity in stratum corneum, with low activities in summer and higher activities in winter for the same person, whereas superoxide dismutase activity in stratum corneum did not seem to vary in those conditions. Exposure of human skin to broadband ultraviolet-A resulted in a dose-dependent deactivation of the catalase activity in stratum corneum within 24 h, whereas exposure to ultraviolet-B had no effect. Superoxide dismutase activity in stratum corneum was not affected by ultraviolet-A or ultraviolet-B irradiation within 24 h. After exposure to a dose of 15 J per cm2 broadband ultraviolet-A, full recovery of the catalase activity occurred in 3-4 wk at an age-dependent rate. We conclude that sun exposure results in a disturbed catalase to superoxide dismutase ratio in the stratum corneum. This may lead to an increased vulnerability to oxidative damage in stratum corneum barrier components. These results therefore stress the importance of providing efficient protection for this internal defense mechanism in sun-exposed areas of the skin.
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PMID:Antioxidant enzyme activity in human stratum corneum shows seasonal variation with an age-dependent recovery. 1260 57

Chronic pancreatitis, K-ras oncogene mutations, and the subsequent generation of reactive oxygen species (ROS) appear to be linked to pancreatic cancer. ROS have also been suggested to be mitogenic and capable of stimulating cell proliferation. Cells contain antioxidant enzymes to regulate steady state levels of ROS produced by products of metabolism. The aims of our study were to determine antioxidant enzyme activity in pancreatic cancer cells and correlate enzyme activity with tumor growth, as well as determine whether tumor cell growth could be altered with antioxidant gene transfection. Western blots, enzyme activity, and enzyme activity gels were performed for manganese superoxide dismutase (MnSOD), copper/zinc, catalase, and glutathione peroxidase in normal human pancreas and in the human pancreatic cancer cell lines BxPC-3, Capan-1, MIA PaCa-2, and AsPC-1. Cell population doubling times were determined and correlated with antioxidant enzyme activity. MnSOD was overexpressed in MIA PaCa-2 using an adenoviral vector, and the effect on cell growth was determined. The cell pancreatic cancer lines BxPC-3, MIA PaCa-2, and AsPC-1 had decreased levels of MnSOD immunoreactive protein as well as activity and decreases in MnSOD levels correlated well with increased rates of tumor cell proliferation as determined by cell doubling time. No correlation could be found between cell growth and levels of copper/zinc superoxide dismutase, catalase, or glutathione peroxidase. Enforced expression of MnSOD by adenovirus transfection in the rapid growing cell line MIA PaCa-2 increased MnSOD immunoreactivity and MnSOD activity and decreased growth rate. Overexpression of MnSOD may be effective in growth suppression of pancreatic cancer.
Cancer Res 2003 Mar 15
PMID:The role of manganese superoxide dismutase in the growth of pancreatic adenocarcinoma. 1264 90

Calcitriol, the hormonal form of vitamin D, enhances the anticancer activity of the immune cytokine tumor necrosis factor, interleukin 1 and interleukin 6 in human breast and renal cell carcinoma cells without affecting the cytotoxic action of interferon-alpha or killer lymphocytes. It also enhances cytotoxicity induced by the anticancer drug doxorubicin, by the redox cycling quinone menadione, and by the reactive oxygen species hydrogen peroxide. The synergistic interaction was accompanied by increased oxidative stress, as manifested by glutathione depletion and was abolished by exposure to the thiol antioxidant N-acetylcysteine. The hormone on its own brought about an increase in the cellular redox state as reflected in the ratio between oxidized and reduced glutathione and glyceraldehyde-3-phosphate dehydrogenase, and a reduction in the expression of the antioxidant enzyme Cu/Zn superoxide dismutase. These results support the notion that the interplay between active vitamin D derivatives and other anticancer agents such as immune cytokines and anticancer drugs plays a role in the in vivo anticancer activity of vitamin D and that reactive oxygen species are involved in the anticancer activity of vitamin D on its own and in its cross-talk with other anticancer modalities.
Recent Results Cancer Res 2003
PMID:The role of reactive oxygen species in the anticancer activity of vitamin D. 1289 35

Thioredoxin reductase (TrxR) in conjunction with thioredoxin (Trx) is a ubiquitous intracellular oxidoreductase system with antioxidant and redox regulatory roles. The properties of TrxR in combination with the functions of Trx position this system at the core of cellular thiol redox control and antioxidant defense. In some human tumors, the thioredoxin system is found over-expressed. Because of its role in stimulating cancer cell growth and as an inhibitor of apoptosis, the Trx system offers a target for the development of drugs to treat and prevent cancer. In a previous research, we successfully synthesized a novel organoselenium compound BBSKE(1,2-[bis(1,2-Benzisoselenazolone-3(2H)-ketone)]ethane, BBSKE, PCT: CN02/00412) targeting the TrxR, and it has demonstrated the inhibitory effect on the growth of a variety of human cancer cells from various organs. In this study, we investigated the inhibitory effect of BBSKE on TrxR activity in PC-3 and DU145 human prostate cancer cell lines, and its antitumoral effect on these two cell lines. Treatment of BBSKE inhibited the TrxR activity in both of the cell lines in a dose-dependent manner and it also inhibited the proliferation of these two cell lines in a dose-dependent manner. Cell cycle analysis showed S phase arrest in both of the cell lines following 48 h exposure to BBSKE. During the S arrest, analysis of cell cycle regulatory proteins demonstrated that BBSKE increased the protein levels of cyclinA, cyclinE, and P21, but decreased the levels of cyclinB1, cyclinD1, and Cdk4. Furthermore, BBSKE decreased the protein level of Bcl-2 but increased the level of Bax, and induced apoptosis in PC-3 and DU145 human prostate cancer cell lines. These results suggest that this novel TrxR inhibitor inhibits the proliferation of prostate cancer cells via S phase arrest and apoptosis in association with the regulation of multiple molecules in the cell cycle.
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PMID:A novel organoselenium compound induces cell cycle arrest and apoptosis in prostate cancer cell lines. 1296 29

The antimalaria drug, artesunate (ART), is very cytotoxic in tumor cell lines. The active moiety of ART is an endoperoxide bridge that generates carbon-centered free radicals and oxidative stress upon cleavage. Oxidative stress appears to be necessary for the antimalarial activity of ART. To test whether antioxidant gene expression affects the ART response in tumor cell lines we compared the baseline antioxidant mRNA gene expression in the 55 human tumor cell line panel from the National Cancer Institute Developmental Therapeutics Program to the ART IC50. Thioredoxin reductase expression showed a significant positive correlation to the ART IC50 and catalase expression was inversely correlated with the ART IC50 (p<0.05). WEHI7.2 mouse thymoma cells selected for resistance to hydrogen peroxide or transfected with thioredoxin, manganese superoxide dismutase, catalase or bcl-2 showed resistance to ART compared to the parental cell line. Taken together these data support a role for oxidative stress in the mechanism of ART action in tumor cells and suggest that antioxidant defenses act in combination to affect the cellular response to ART.
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PMID:Role of antioxidant genes for the activity of artesunate against tumor cells. 1296 9

NQO1 is an antioxidant enzyme, important in the detoxification of environmental carcinogens. A single nucleotide polymorphism (C-->T) at position 609 of the NQO1 cDNA has been associated with susceptibility to tumours induced by chemical carcinogens. In our case-control study, we determined the prevalence of the C609T NQO1 polymorphism by PCR-RFLP analysis in Caucasian patients with oesophageal adenocarcinoma (OAC; n=61), cardiac adenocarcinoma (CAC; n=120) or gastric adenocarcinoma (GAC; n=203) vs. a control group that consisted of 252 healthy blood donors. Additionally, NQO1 mRNA expression and NQO1 protein expression were determined by RT-PCR and immunohistochemistry in a subset of cases. The NQO1 C609T genotype distribution was significantly different among controls (C/C, 73.4%; C/T, 25.0%; T/T, 1.6%) as compared to OAC patients (C/C, 49.2%; C/T, 47.5%; T/T, 3.3%; p=0.0004), CAC patients (C/C, 55.8%; C/T, 40.0%; T/T, 4.2%; p=0.0005) and with GAC patients (C/C, 65.5%; C/T; 30.6%, T/T; 3.9%; p=0.0377). The 609T allele overall frequency was 0.141 in controls, 0.270 in OAC patients, 0.241 in CAC patients and 0.192 in GAC patients. Individuals carrying 1 or 2 609T alleles had a 2.85-fold higher risk (95% CI: 1.61-5.07; p=0.0003) for the development of OAC and a 2.18-fold higher risk (95% CI: 1.38-3.44; p=0.0007) for the development of CAC than wild-type gene homozygotes. Immunohistochemical analysis showed NQO1 protein expression in 133 carcinomas, whereas 17 carcinomas were negative. Negativity for NQO1 protein expression correlated strongly with the NQO1 genotype being present in 3.9% of cases with C/C, 13.9% of cases with C/T and 62.5% of cases with T/T genotype (p<0.001). In contrast, NQO1 mRNA expression was detectable irrespective of underlying genotype. In conclusion, determination of the NQO1 genotype may gain importance as a stratification marker in future prevention trials for adenocarcinoma of upper gastrointestinal tract.
Int J Cancer 2003 Nov 10
PMID:Association between NAD(P)H: quinone oxidoreductase 1 (NQ01) inactivating C609T polymorphism and adenocarcinoma of the upper gastrointestinal tract. 1450 37

The pharmacological properties of garlic and its derivatives are long known, and their underling mechanisms are being extensively investigated. In this study we have addressed the effects of diallyl disulfide (DADS), an oil-soluble garlic molecule, on cell growth of neuroblastoma cell SH-SY5Y, focusing on the redox events associated with this compound. Treatment of SH-SY5Y cells with DADS resulted in arrest of cell cycle in G(2)/M phase and commitment to apoptosis through the activation of the mitochondrial pathway (Bcl-2 down-regulation, cytochrome c release into the cytosol, and activation of caspase-9 and caspase-3). The earliest oxidative event observed after DADS treatment was the increase of production of reactive oxygen species, which reached the maximum yield on 30 min of DADS treatment. The oxidative burst resulted in protein and lipid damage as demonstrated by protein carbonyl accumulation and lipid peroxidation. We demonstrated that apoptosis induction was highly dependent on the activation of the redox-sensitive c-Jun NH(2)-terminal kinase (JNK)/c-Jun pathway. In particular, we established that DADS treatment induces JNK dissociation from glutathione S-transferase and its activation by phosphorylation. Moreover, treatment with JNK inhibitor I significantly reduced DADS-induced apoptosis and treatment with the spin trap 5,5'-dimethyl-1-pyrroline N-oxide or overexpression of the antioxidant enzyme copper, zinc superoxide dismutase, resulted in the inhibition of DADS-mediated toxicity through attenuation of JNK/c-Jun pathway activation. Overall, the results suggest a pivotal role for oxidative stress in DADS-induced apoptosis and, taking into account that tumor cells are deficient in antioxidants, suggest a plausible utilization of this compound as an antiproliferative agent in cancer therapy.
Cancer Res 2003 Sep 15
PMID:Reactive oxygen species-dependent c-Jun NH2-terminal kinase/c-Jun signaling cascade mediates neuroblastoma cell death induced by diallyl disulfide. 1452 20

Carboplatin is currently being used as an anticancer drug against human cancers. However, high dose of carboplatin chemotherapy resulted in ototoxicity in cancer patients. Carboplatin-induced ototoxicity was related to oxidative stress to the cochlea and inner hair cell loss in animals. It is likely that initial oxidative injury spreads throughout the neuroaxis of the auditory system later. The study aim was to evaluate carboplatin-induced hearing loss and oxidative injury to the central auditory system (inferior colliculus) of the rat. Male Wistar rats were divided into two groups of seven animals each and treated as follows: (1) control (normal saline, intraperitoneal [i.p.]) and (2) carboplatin (256 mg/kg, i.p.). Auditory brain-evoked responses (ABRs) were recorded before and 4 days after treatments. The animals were sacrificed on the 4th day and inferior colliculus from brain stem and cerebellum were isolated and analyzed. Carboplatin significantly elevated the hearing threshold shifts at clicks, 2-, 4-, 8-, 16-, and 32-kHz tone burst stimuli. Carboplatin significantly increased nitric oxide and lipid peroxidation, xanthine oxidase, and manganese superoxide dismutase activities in the inferior colliculus, but not in the cerebellum, indicating an enhanced flux of free radicals in the central auditory system. Carboplatin significantly depressed the reduced to oxidized glutathione ratio, antioxidant enzyme activities, such as copper-zinc superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and enzyme protein expressions in the inferior colliculus, but not in the cerebellum, 4 days after treatment. The data suggest that carboplatin induced oxidative injury specifically in the inferior colliculus of the rat leading to hearing loss.
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PMID:Carboplatin-induced oxidative injury in rat inferior colliculus. 1455 5


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