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)

Immunogold studies of normal human kidney and common human kidney cancers were performed using polyclonal antibodies to antioxidant enzymes, including antibodies to copper, zinc and manganese superoxide dismutases, catalase, glutathione peroxidase, and glutathione S-transferases and their subunits. Normal tissue adjacent to human renal tumors had the same antioxidant enzyme immunoreactive protein profiles as normal human kidney, thus establishing that the presence of tumor does not alter the levels of antioxidant enzyme immunoreactive proteins in adjacent kidney tissue. Levels of immunoreactive protein for antioxidant enzymes were determined in four common types of malignant renal cancer. In general, tumors had low levels of antioxidant enzymes; however, certain histologic types of renal tumors had high levels of immunoreactive protein for glutathione S-transferase subunits, which could affect their susceptibility to chemotherapy. Studies of transitional carcinoma of the renal pelvis were especially informative since it was possible to compare levels of antioxidant enzyme immunoreactive protein with adjacent normal transitional epithelium; the majority of antibodies resulted in lower levels of immunoreactive protein in transitional cell carcinoma than in adjacent normal transitional epithelium. Our results are discussed in relation to the response of renal tumors to therapy.
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PMID:Immunogold analysis of antioxidant enzymes in common renal cancers. 872 Apr 59

The levels of the antioxidant enzyme manganese superoxide dismutase (Mn-SOD) are frequently decreased in tumor cells and increased in normal cells upon treatment with ionizing radiation. We studied Mn-SOD at different stages during the neoplastic conversion of radiation-initiated Syrian hamster embryo HDR-3 cells. Mn-SOD activity and the concentration of Mn-SOD protein and mRNA increased gradually during the malignant transformation of HDR-3 cells after radiation exposure; fully neoplastic cells showed greater Mn-SOD levels than preneoplastic and normal 84-3 cells. Inhibitors of superoxide (SO) anion production (thenoyltrifluoroacetone and rotenone) decreased the concentration of Mn-SOD mRNA, raising the possibility that the generation of SO radicals participated in the upregulation of Mn-SOD in cells transformed by exposure to radiation. We observed an increase in the concentration of tumor necrosis factor alpha (TNF alpha) in HDR-3 cells relative to mock-irradiated cells. Together with the observation that TNF alpha stimulates the production of SO by mitochondria and increases the level of Mn-SOD mRNA in other experimental systems, our results suggest that as normal 84-3 cells undergo malignant transformation induced by ionizing radiation they produce TNF alpha, to which the cells respond by increasing the concentration of Mn-SOD mRNA and protein and the activity of the enzyme.
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PMID:Increased manganese superoxide dismutase activity, protein, and mRNA levels and concurrent induction of tumor necrosis factor alpha in radiation-initiated Syrian hamster cells. 898 10

Thioredoxin and thioredoxin reductase are redox proteins that have been implicated in the control of cell proliferation and transformation. We report the levels and activity of these proteins and their mRNAs in human primary tumors and tumor cell lines. Half of human primary colorectal carcinomas (5/10) examined had increased thioredoxin mRNA, of 3- to over 100-fold, compared to adjacent normal colonic mucosa from the same subject. Thioredoxin reductase protein and activity were increased an average of 2-fold in human colorectal tumors compared to normal mucosa. A number of human hematologic and solid tumor cell lines were studied and showed a 10-fold range of thioredoxin mRNA and a 23-fold range of thioredoxin reductase mRNA. Increased proliferation and hypoxia are factors that might contribute to the increased expression in solid tumors. We found that serum stimulation of growth arrested MCF-7 breast cancer cells caused a 59% increase in thioredoxin mRNA and a 62% increase in thioredoxin reductase mRNA by 24 hours. Exposure of HT-20 colon cancer cells to hypoxia resulted in a 14-fold increase in thioredoxin mRNA by 16 hours, and a transient 4-fold increase in thioredoxin reductase mRNA at 1 hour that had returned to control levels by 8 hours. Cancer cells were found to release thioredoxin into the medium at rates between 1 to 2 pmole/10(6) cells/3 hours. The rate of secretion was not, however, related to cellular-levels of thioredoxin. The results of the study show that the expression of thioredoxin and thioredoxin reductase are increased several fold in some human solid tumors compared to normal tissue. Secretion of thioredoxin, which is known to have a direct growth stimulating activity, by human tumor cells might lead to the stimulation of cancer cell growth.
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PMID:Thioredoxin and thioredoxin reductase gene expression in human tumors and cell lines, and the effects of serum stimulation and hypoxia. 904 7

Normal cells are protected by antioxidant enzymes from the toxic effects of high concentrations of reactive oxygen species generated during cellular metabolism. Even though cancer cells generate reactive oxygen species, it has been demonstrated biochemically that antioxidant enzyme levels are low in most animal and human cancers. However, a few cancer types have been found to have elevated levels of antioxidant enzymes, particularly manganese superoxide dismutase. Morphologic studies of animal and human cancer have confirmed that although the majority of tumor cell types from several organ systems have low antioxidant enzymes, adenocarcinomas may have elevated manganese superoxide dismutase and catalase levels. However, all cancers examined to date have some imbalance in antioxidant enzyme levels compared with the cell of origin. Antioxidant enzyme importance in cancer genesis has been difficult to evaluate in early cancerous lesions using biochemical techniques because such lesions are small and therefore below the level of detection. Using immunohistochemical techniques, early lesions of human and animal cancers were demonstrated to have low antioxidant enzymes, thus suggesting a role for these enzymes both in the genesis of cancer and the malignant phenotype. All but one human cancer cell type (the granular cell variant of human renal adenocarcinoma) examined showed both low catalase and glutathione peroxidase levels, suggesting that most cancer cell types cannot detoxify hydrogen peroxide. Our results to date are used to propose new cancer therapies based on modulation of cellular redox state.
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PMID:Antioxidant enzyme levels in cancer. 915 Nov 41

To determine whether non-hematologic tumors influence the bone marrow's antioxidant enzyme response to the radioprotective cytokine interleukin 1 alpha (IL-1), studies were undertaken using BDF1 and Balb/c mice bearing small, medium or large Lewis lung carcinoma (LLCa) or EMT6 mammary carcinoma tumors, respectively. Results demonstrated that, similar to nontumor-bearing mice, treatment of tumor-bearing animals with IL-1 was associated with a significant increase in marrow MnSOD activity. However, the duration of this elevated activity was reduced as tumor burden increased, and this reduction may have an impact on IL-1's ability to radioprotect tumor bearing animals, especially when tumor burden is large. In addition to cytokine-mediated responses, significant tumor-related influences on the marrow's antioxidant enzyme status were seen. Notably, it was observed that the presence of tumor was correlated with a marked suppression of antioxidant enzyme activity. Surprisingly, however, the pattern of enzyme suppression was found to differ between the two tumor models studied both in temporal onset and in the number of enzymes involved. In conclusion, the data obtained from these studies on tumor-bearing animals demonstrate that there are both cytokine-related and tumor-related influences which can effect the antioxidant enzyme status of the hematopoietic marrow-influences which may have the potential to alter the marrow's ability to tolerate free radical-generating events, both endogenous (i.e inflammation, infection) and exogenous (i.e. radiation, certain chemotherapeutic drugs) in origin.
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PMID:Antioxidant enzyme activity in murine hematopoietic bone marrow following treatment with interleukin 1 alpha: influence of tumor. 921 82

Among many pharmaceuticals that have been tested for their effects on longevities of different animal rodents, deprenyl is unique in that its effects on longevity has been tested in at least four different animal species by independent research groups and that the effect has been postulated to be due to its effect of raising such antioxidant enzyme activities as superoxide dismutase (SOD) and catalase (CAT) in selective brain regions. Thus far, in all four species of animals examined (rats, mice, hamsters, and dogs), a positive effect was demonstrated, although the extent of its effect is quite variable. Our group has examined the effect on longevities in rats and mice and on antioxidant enzymes in rats, mice, and dogs. Although in rats of both sexes, we have obtained positive effects on longevity, two studies with different doses in mice did not reveal a significantly positive effect. We have observed, however, significantly positive effects on SOD (in Cu, Zn-, and Mn-) as well as CAT (but not glutathione peroxidase) activities in the brain dopaminergic system such as in the S. nigra and striatum (but not in hippocampus) in all rats, mice, and dogs, although the effects were quite variable, depending on the doses used. In mice, however, a long-term administration (3x/w, 3 months) caused a remarkable decrease in the magnitude of activity as well as a narrowing of the effective dose range, which may explain a relatively weak effect of the drug on mouse longevity. Further, a recent study on aging beagle dogs by Ruehl et al. showed a remarkable effect on longevity, which agrees with our SOD study in dogs. Although deprenyl has been claimed to have several other effects, such as a radical scavenging effect and a neuroprotective effect, past reports on its effects on longevities and antioxidant defenses are compatible with the notion that the drug prolongs the life span of animals by reducing the oxidative damage to the brain dopaminergic system during aging. Further, our studies on F-344 rats as well as a dog study by Ruehl et al. suggest that the drug may at least partially prolong the life span of animals by enhancing immune system function and preventing tumor development in animals.
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PMID:Assessing the effects of deprenyl on longevity and antioxidant defenses in different animal models. 992 38

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the hormonal form of vitamin D, has anticancer activity in vivo and in vitro. Doxorubicin exerts its cytotoxic effect on tumor cells mainly by two mechanisms: (a) generation of reactive oxygen species (ROS); and (b) inhibition of topoisomerase II. We studied the combined cytotoxic action of 1,25(OH)2D3 and doxorubicin on MCF-7 breast cancer cells. Pretreatement with 1,25(OH)2D3 resulted in enhanced cytotoxicity of doxorubicin. The average enhancing effect after a 72-h pretreatment with 1,25(OH)2D3 (10 nM) followed by a 24-h treatment with 1 microg/ml doxorubicin was 74+/-9% (mean +/- SE). Under these experimental conditions, 1,25(OH)2D3 on its own did not affect cell number or viability. 1,25(OH)2D3 also enhanced the cytotoxic activity of another ROS generating quinone, menadione, but did not affect cytotoxicity induced by the topoisomerase inhibitor etoposide. The antioxidant N-acetylcysteine slightly reduced the cytotoxic activity of doxorubicin but had a marked protective effect against the combined action of 1,25(OH)2D3 and doxorubicin. These results indicate that ROS are involved in the interaction between 1,25(OH)2D3 and doxorubicin. 1,25(OH)2D3 also increased doxorubicin cytotoxicity in primary cultures of rat cardiomyocytes. Treatment of MCF-7 cells with 1,25(OH)2D3 alone markedly reduced the activity, protein, and mRNA levels of the cytoplasmic antioxidant enzyme Cu/Zn superoxide dismutase, which indicated that the hormone inhibits its biosynthesis. This reduction in the antioxidant capacity of the cells could account for the synergistic interaction between 1,25(OH)2D3 and doxorubicin and may also suggest increased efficacy of 1,25(OH)2D3 or its analogues in combination with other ROS-generating anticancer therapeutic modalities.
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PMID:1,25-Dihydroxyvitamin D3 enhances the susceptibility of breast cancer cells to doxorubicin-induced oxidative damage. 1002 76

An investigation was made of ethoxyresorufin O-deethylase (EROD) activity, a cytochrome P450 (CYP) dependent enzyme mainly catalyzed by CYP1A1, glutathione S-transferase (GST) activity toward the substrates 1-chloro-2,4- dinitrobenzene (CDNB) and ethacrynic acid (EAA), reduced glutathione (GSH) levels, and antioxidant enzyme (AOE) activity namely catalase (CAT) and selenium- dependent glutathione peroxidase (Se-GPx) in tumor and surrounding tumor-free (normal) tissues in female breast cancer patients. Wide interindividual variations were found in the enzyme activities in both tumor and normal breast tissues. No significant differences were noted between mean EROD and CAT activities in tumor and normal breast tissues. The mean activities of CDNB GST, EAA GST and Se-GPx and GSH levels in tumor tissue were significantly higher than those in normal breast tissue. These results show that CYP, GST and AOE behave differentially in breast tumors.
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PMID:Xenobiotic metabolizing and antioxidant enzymes in normal and neoplastic human breast tissue. 1032 33

In order to decrease toxicity and/or increase radiosensitizing activity, a new 2-nitroimidazole derivative, methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804), was synthesized to solve the problem of tumor hypoxia. Evaluation of the efficiency of KIN-804 was carried out through studying the antioxidant enzyme system: The superoxide dismutase (SOD), catalase and lipid peroxide levels provide a rough index of the balance between free radical generation and scavenging. Female albino mice were inoculated with Ehrlich ascites carcinoma (EAC) in the thigh. The administration of KIN-804 (i.p. 80 mg/kg body weight) was carried out 20 min before localized irradiation of 10 Gy. In general, the data revealed that KIN-804 administration, followed or not by gamma irradiation, exerted significant inhibition of SOD and catalase activities accompanied by a significant increase in lipid peroxide level in tumor-bearing mice.
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PMID:Studies of methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) 2: effect on certain antioxidant enzyme systems in mice bearing Ehrlich ascites carcinoma. 1070 83

In this communication, we investigate the preventive effect of a flavonoid antioxidant, silymarin, on free radical-generating skin tumor promoting agent benzoyl peroxide (BPO)-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. Topical application of silymarin at a dose of 6 mg prior to BPO resulted in a highly significant protection against BPO-induced tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated SENCAR mouse skin. The preventive effect of silymarin was evident in terms of a 70% reduction (P < 0.001) in tumor incidence, a 67% reduction (P < 0.001) in tumor multiplicity and a 44% decrease (P < 0.001) in tumor volume/tumor. In oxidative stress studies, topical application of BPO resulted in 75, 87 and 61% depletion in superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) activities in mouse epidermis, respectively. These decreases in antioxidant enzyme activities were significantly (P < 0.005-0.001) reversed by pre-application of silymarin in a dose-dependent manner. The observed effects of silymarin were 18-66, 32-72 and 20-67% protection against BPO-induced depletion of SOD, catalase and GPX activity in mouse epidermis, respectively. Silymarin pre-treatment also resulted in a dose-dependent inhibition (35-87%, P < 0.05-0. 001) of BPO-induced lipid peroxidation in mouse epidermis. In inflammatory response studies, silymarin showed a strong inhibition of BPO-induced skin edema (62-85% inhibition, P < 0.001), myeloperoxidase activity (42-100% inhibition, P < 0.001) and interleukin-1alpha protein level in epidermis (36-81% inhibition, P < 0.001). These results, together with our other recent studies, suggest that silymarin could be useful in preventing a wide range of carcinogen and tumor promoter-induced cancers.
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PMID:Inhibitory effect of a flavonoid antioxidant silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. 1075 20


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