Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Individual response to oxidative stress, due to exposure to asbestos fibres plays a significant role in the malignant pleural mesothelioma (MPM) etiology. The differential impact on MPM risk of polymorphic alleles of glutathione-S-transferases (GSTs) and manganese superoxide dismutase (MnSOD/SOD2) genes involved in the defence against oxidative damage has been investigated. Ninety cases of MPM and 395 controls were genotyped using the arrayed-primer extension technique. Logistic regression analysis was applied to assess the predictive role of single nucleotide polymorphisms (SNPs) potentially involved in MPM carcinogenesis after adjustment for potential confounders. An increased risk of MPM was found in subjects bearing a GSTM1 null allele (OR = 1.69, 95% CI = 1.04-2.74; p = 0.034), and in those with the Ala/Ala genotypes at codon 16 within MnSOD (OR = 3.07, 95% CI = 1.55-6.05; p = 0.001). A stronger effect of MnSOD was observed among patients without a clear exposure to asbestos fibres. No effect was found for GSTA2, GSTA4, GSTM3, GSTP1 and GSTT1 genes. These findings, if replicated, contribute substantial evidence to the hypothesis that oxidative stress and cellular antireactive oxygen species systems are involved in the pathogenesis and in the natural history of MPM.
Int J Cancer 2007 Jun 15
PMID:Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma. 1729 Mar 92

Glutathione S transferases (GSTT1, GSTM1, GSTP1) are enzymes that activate the detoxification of endogenous and exogenous agents. The genetic polymorphism in these genes may change the response of individuals to environmental toxicants. The genetic polymorphisms of GSTT1, GSTM1, GSTP1 have been studied extensively in the determination of individual cancer risks. Some studies showed a strong relationship between polymorphism of GSTs and superoxidedismutase enzymes. Using the polymerase chain reaction (PCR) the prevalence of genetic polymorphisms of GSTT1, GSTM1 and MnSOD (Manganese Superoxide Dismurase) was investigated in 104 cases and controls to seek any association with the risk of bladder cancer. The frequency of GSTT1 +/+ polymorphism was 65% (33/51) in the cases and 79% (42/53) in the controls. The frequency of the GSTM1 +/+ polymorphism was 33% (17/51) in the cases and 58% (31/53) in the controls. The frequency of the GSTM1 null genotype was 42% (22/53) in the controls and 68% (34/51) in the patients. The frequency of the SOD AA genotype was 36% (17/51) in the cases and 33% (19/53) in the controls. There was no association between the GSTT1 and SOD polymorphism and bladder cancer incidence. The incidence of the GSTM1 null genotype was increased in bladder cancer patients compared to controls (OR = 1.755, 95% CI = 1.119-2.751).
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PMID:The investigation of GSTT1, GSTM1 and SOD polymorphism in bladder cancer patients. 1734 Feb 8

Administration of manganese superoxide dismutase-plasmid liposomes (MnSOD-PL) has been demonstrated to provide local radiation protection to the lung, esophagus, oral cavity, urinary bladder and intestine. Radiation protection has been shown to be mediated in part by MnSOD stabilization of the antioxidant pool including glutathione and total thiols within cells and in normal tissues. In experiments to determine whether organ-specific radioprotection would also protect orthotopic tumors, mice with Lewis lung carcinoma orthotopically placed at the carina or in other experiments with mice with cheek pouch placed SCCVII orthotopic squamous cell tumors demonstrated paradoxical and beneficial tumor radiosensitization following intratracheal or intraoral MnSOD-PL, respectively. The mechanism of MnSOD-PL tumor radiosensitization may involve a difference in redox balance between tumors and normal tissues. Differences in handling radiation-induced oxidative stress between tumors and normal tissues can provide a fundamental basis to design new cancer therapeutic agents which can exploit differences between normal tissue and tumor mechanisms of handling the oxidative stress of ionizing irradiation damage.
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PMID:Review. Antioxidant gene therapeutic approaches to normal tissue radioprotection and tumor radiosensitization. 1743 62

Archived tumor tissue is a useful resource for retrospective studies addressing relationships between genetic polymorphisms and treatment outcomes. However, genotypes determined in tumor and somatic tissues may differ due to cytogenetic and molecular changes associated with malignant transformation and progression. Discordance between germ line and tumor genotypes may be particularly relevant in leukemia because cytogenetic abnormalities are frequent. We compared genotypes determined in DNA extracted from paired pretreatment bone marrow and buccal samples from 80 adult patients with acute myeloid leukemia (AML). Paired AML and buccal DNA samples were genotyped for polymorphisms (21 single nucleotide polymorphisms and 2 gene deletions) on genes encoding proteins involved in drug metabolism (CYP3A4, CYP2C8, CDA, and GSTP1), oxidative stress mechanisms (CAT, MnSOD, GSTT1, GSTM1, GSTA1, and GPX1), drug transport (MDR1, MRP1, and BCRP), and DNA repair (MGMT, XPD, and XRCC1). Genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, except GSTM1 and GSTT1, for which deletion genotypes were determined using multiplex PCR. Concordance of genotypes was tested by kappa statistics. kappa statistics for paired AML and buccal DNA samples ranged between 0.94 and 1.00, indicating excellent agreement. The GSTT1 and GSTM1 genotypes were in perfect concordance for the paired samples. Agreement was also excellent for genes at AML chromosome deletion and translocation breakpoints, including MDR1 at 7q21.1 and MRP1 at 16p13.1. Based on these data, genotypes derived from archived AML bone marrow samples were not likely to differ from those from genomic DNA, and archived bone marrow samples may be useful for the conduct of retrospective pharmacogenetic studies.
Cancer Epidemiol Biomarkers Prev 2007 May
PMID:Concordance of pharmacogenetic polymorphisms in tumor and germ line DNA in adult patients with acute myeloid leukemia. 1750 36

Oxidative stress, associated with aging and inflammation, is likely to play a role in the etiology of prostate cancer. We evaluated potential associations between gene variants that result in reduced neutralization of reactive oxygen species (ROS; MnSOD Ala-16Val, CAT -262 C>T, and GPX1 Pro200Leu) and prostate cancer risk among 724 men with incident prostate cancer who participated in the Carotene and Retinol Efficacy Trial (CARET) cohort, a randomized trial for the prevention of lung cancer among men with a history of smoking and/or asbestos exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression. Nested case-control analyses included study participants with available DNA (n = 533 cases and 1,470 controls), matched for race, age, and length of follow-time. Overall, there were no associations between genotypes of MnSOD, CAT, and GPX1 and prostate cancer risk, although among men diagnosed before age 65, CAT TT genotype was associated with increased risk (OR, 2.0; 95% CI, 0.97-3.95). Further analyses stratified by factors related to environmental oxidative stress exposures did not modify associations. When calculating the number of risk alleles of MnSOD, CAT, and GPX1 hypothetically related to reduced protection against ROS, there was a nonsignificant relationship between prostate cancer and carriage of five or more risk alleles, in comparison to men with less than five risk alleles (OR, 2.0; 95% CI, 0.90-4.42). In conclusion, it does not seem that variants in MnSOD, CAT, or GPX1 have an influence on prostate cancer risk in this cohort of men who were smokers or exposed to asbestos, although it is possible that cumulative defects in protection from oxidative stress may result in increased risk of the disease.
Cancer Epidemiol Biomarkers Prev 2007 Jun
PMID:Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers. 1754 72

Nuclear factor-kappaB provides an adaptive response to protect cancer cells against cytotoxicity induced by redox active therapeutics. RelB is uniquely expressed at a high level in prostate cancer with high Gleason scores. Recently, we showed that the level of RelB rapidly increases in androgen-independent prostate cancer cells after exposure to ionizing radiation (IR), leading to a reduction in intrinsic radiosensitivity. Here, we show that interaction of 1alpha,25-dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)] with the vitamin D receptor significantly enhances radiosensitivity of prostate cancer cells at clinically relevant radiation doses. The radiosensitization effect of 1alpha,25-(OH)(2)D(3) is mediated, at least in part, by selectively suppressing IR-mediated RelB activation, leading to a reduced expression of its target gene MnSOD, a primary antioxidant enzyme in mitochondria. These results suggest that suppression of manganese superoxide dismutase is a mechanism by which 1alpha,25-(OH)(2)D(3) exerts its radiosensitization effect and that 1alpha,25-(OH)(2)D(3) may serve as an effective pharmacologic agent for selectively sensitizing prostate cancer cells to IR via suppression of antioxidant responses in mitochondria.
Mol Cancer Ther 2007 Jul
PMID:Suppression of RelB-mediated manganese superoxide dismutase expression reveals a primary mechanism for radiosensitization effect of 1alpha,25-dihydroxyvitamin D(3) in prostate cancer cells. 1760 35

Superoxide dismutase (SOD) plays a key role in the detoxification of superoxide free radicals. We evaluated the association of prostate cancer with genetic polymorphisms in SOD1 (CuZn-SOD; IVS3-251A>G), SOD2 [MnSOD; Ex2+24T>C (V16A)], and SOD3 (EC-SOD; IVS1+186C>T, Ex3-631C>G, Ex3-516C>T, and Ex3-489C>T), the three main isoforms of SOD. Prostate cancer cases (n = 1,320) from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were frequency matched to nondiseased controls (n = 1,842) by age, race, time since initial screening, and year of blood draw. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI); stratified analysis by the level of antioxidative vitamins was also conducted. The higher activity Ala variant at SOD2 Ex2+24T>C (V16A), which has been hypothesized to suppress prostate carcinogenesis, was associated with elevation of prostate cancer risk in Caucasians (Val/Ala versus Val/Val: OR, 1.17; 95% CI, 0.97-1.42; Ala/Ala versus Val/Val: OR, 1.28; 95% CI, 1.03-1.60; P(trend) = 0.03). Stratification by quartiles of dietary and supplemental vitamin E intake (IU/d) showed risks of prostate cancer tended to be increased among SOD2 Ala allele carriers, except at the highest quartile of vitamin E intake (>222; P(interaction) = 0.06, Q1-Q3 versus Q4). The association between Ala allele and prostate cancer risk among those with lower intake of vitamin E (</=222) was stronger for smokers (OR, 1.44; 95% CI, 1.10-1.90). No significant association with prostate cancer was observed for polymorphic variants in SOD3 or SOD1. These results suggest that the Ala variant of SOD2 is associated with moderately increased risk of prostate cancer, particularly among men with lower intakes of dietary and supplemental vitamin E.
Cancer Epidemiol Biomarkers Prev 2007 Aug
PMID:Functional variant of manganese superoxide dismutase (SOD2 V16A) polymorphism is associated with prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer study. 1764 72

The antiproliferative and cytotoxic potential of the natural anthracycline aloin from Aloe vera was tested on human uterine carcinoma HeLaS3 cells. Aloin showed a pronounced antiproliferative effect at physiological concentration (IC50 = 97 microM), caused cell cycle arrest in the S phase and markedly increased HeLaS3 cell apoptosis (to 24%). In the concentration range of 20-100 microM, its action was accompanied by remarkable changes in the activity of almost all antioxidant enzymes: MnSOD activity was increased many fold, while CuZnSOD and iNOS activities were inhibited. Moreover, inhibition of CuZnSOD was shown to occur by direct aloin interaction with the enzyme. As catalase activity was not changed, it is suggested that such conditions were responsible for antiproliferative and cytotoxic effects owing to accumulation of H2O2. Aloin alone was a more potent proapoptotic agent than a 2 Gy fractional dose of ionizing radiation or a combination of the two. Compared to other currently used therapeutics, aloin, due to its less undesirable side effects and antimetastatic potential, may prove to be the agent of choice on which clinical protocols for the treatment of human cervical carcinoma should rely in future.
Cancer Biol Ther 2007 Aug
PMID:Antitumor effects of a natural anthracycline analog (Aloin) involve altered activity of antioxidant enzymes in HeLaS3 cells. 1772 68

The objective of this study was to determine in a rat model of hepatocarcinoma (HCC) the effects of the antiangiogenic agent TNP-470 on antioxidant enzymes, including catalase (CAT), superoxide dismutases (Mn-SOD and Cu,Zn-SOD), and glutathione peroxidase (GPx). Tumor was induced in male Wistar rats by diethylnitrosamine and promoted by two-thirds hepatectomy plus acetaminofluorene administration. Experiments were carried out 28 weeks after initiating the treatment. TNP-470 was administered at 30 mg/kg, 2 times per week from weeks 20 to 28. Carcinomatous tissue was growing outside dysplastic nodules in rats with HCC. HCC caused oxidative stress demonstrated by increased lipid peroxidation and oxidized/reduced glutathione ratio that was accompanied by a reduced activity of antioxidant enzymes Cu,Zn-SOD, GPx, and CAT. In contrast, Mn-SOD activity and expression were higher in hepatocarcinoma than in control groups. These effects were absent in animals receiving TNP-470. No significant differences between untreated and TNP-470-treated rats were observed in the expression of the Cu,Zn-SOD, glutathione peroxidise, and CAT. We conclude that TNP-470 inhibits expression and activity of Mn-SOD induced by experimental hepatocarcinogenesis. Oxidative stress reduction by TNP-470 accounts for yet another anti-cancer effect of this molecule.
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PMID:Changes in the antioxidant system by TNP-470 in an in vivo model of hepatocarcinoma. 1776 72

The involvement of mitochondrial glycerophosphate dehydrogenase (mGPDH) has previously been established in the production of ROS in prostate cancer cell lines (LNCaP, DU145, PC3 and CL1). The current study demonstrates that the mRNA level of mGPDH in prostate cancer cells is 3.3-8.9-fold higher compared to the normal prostate epithelial cell line, PNT1A. This is consistent with the enzymatic activity and protein level of mGPDH. However, cytochrome c oxidase (COX) activity is 2.9-3.2-fold down-regulated in androgen-independent prostate cancer cell lines. The level of antioxidant enzymes, catalase, MnSOD and CuZnSOD are up-regulated in prostate cancer cell lines. Furthermore, it was observed that the activity of mGPDH is significantly higher in liver tissues from all mice with cancer compared to liver tissues from control mice. These data suggest that the up-regulation of mGPDH, due to a highly glycolytic environment, contributes to the overall increase in ROS generation and may result in the progression of the cancer.
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PMID:Increased expression of mitochondrial glycerophosphate dehydrogenase and antioxidant enzymes in prostate cancer cell lines/cancer. 1788 33


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