Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plant-derived phenolic compounds manifest many beneficial effects and can potentially inhibit several stages of carcinogenesis. In the present study, we investigated the efficacy of Emblica officinalis (E. officinalis) polyphenol fraction (EOP) on the induction of apoptosis in mouse and human carcinoma cell lineses and its modulatory effect on N- nitrosodiethylamine (NDEA) induced liver tumors in rats. The results indicate that EOP treatment could induce apoptosis in Dalton's Lymphoma Ascites (DLA) and CeHa cell lines At 200 microg/ml dose EOP induced membrane blebbing, chromatin condensation and intenucleosomal breaks as evident from the morphology and DNA ladder pattern obtained in gel electrophoresis. The results also suggested that EOP treatment could decrease the liver tumour development induced by NDEA. Animals administered (oral) with NDEA (0.02%, 2.5 ml/rat, 5 days a week, 20 weeks) developed visible liver tumours by the end of the 20th week and the liver weight raised to 5.2 +/- 1.1 g/ 100 g body weight. Only 11% of the animals treated with EOP (60 mg/kg, oral, 5 days a week for 20 weeks) developed visible liver tumours by this period and the liver weights were reduced to 3.2 +/- 0.7 g/ 100 g body weight. gamma-glutamyl transpeptidase activity was raised to 88.4 +/- 16.2 U/l in serum of NDEA treated group was reduced to 48.4 +/- 14.8 U/l by EOP treatment. Elevated levels of serum alkaline phosphatase (ALP), glutamate pyruvate transaminase (GPT), bilirubin, liver glutathione S-transferase (GST) and glutathione (GSH) in the NDEA administered group were significantly reduced by EOP treatment. The EOP was found to scavenge superoxide and hydroxyl radicals and inhibit lipid peroxidation in vitro. EOP also inhibited DNA topoisomerase I in Saccharomyces cervisiae mutant cell cultures and the activity of cdc25 tyrosine phosphatase.
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PMID:Induction of apoptosis in mouse and human carcinoma cell lines by Emblica officinalis polyphenols and its effect on chemical carcinogenesis. 1286 70

The present research establishes standard two-dimensional (2-D) maps for control, reactive lymph node and non-Hodgkin's lymphoma (mantle cell lymphoma, MCL). Medium sensitivity, mass spectrometry compatible colloidal Coomassie has revealed a total of ca. 750 spots in each of the maps. Comparison of 2-D maps by statistical packages, such as the PDQuest, established up- and downregulation of a total of ca. 145 spots, with positive variations of up to 10-folds and negative variations of up to 13-folds in both MCL biopsies' protein extracts. Qualitative and quantitative variations in the two lymphoma samples are consistent. More than 20 proteins have been so far identified by matrix assisted laser desorption/ionisation-time of flight (MALDI-TOF)-mass spectrometry, with an additional five spots, which gave very good spectra but could not be matched to any of the presently available databases. Some of the spots, such as the 78 kDa glucose-regulated protein precursor and the glutathione S-transferase P, appear to be in common with other tumors, such as lung adenocarcinoma. Others may simply reflect overall changes in cellular metabolism and growth rate that occur during malignancy and thus might turn out to be in common with any cell population receiving any kind of stress. Some (notably T-cell leukemia/lymphoma protein 1A, TCL1, found to be 10-fold overexpressed) appear to be specific of the non-Hodgkin's lymphoma here studied. Western blot and immunohistochemical analyses were applied to obtain further information about stathmin (Op18) and TCL1, respectively.
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PMID:Two-dimensional molecular profiling of mantle cell lymphoma. 1287 73

The leukocyte specific protein 1 or LSP1 is a multi functional protein involved in such divers biological processes as the regulation of neutrophil motility, chemotaxis, adhesion and membrane immunoglobulin M (mIgM) mediated apoptosis of B-lymphocytes. The 330-amino-acid mouse LSP1 protein contains a high-affinity F-actin binding site and in intact cells localizes to the F-actin filament containing cytoskeleton. Here we use a high-speed F-actin co sedimentation assay and transfection experiments in the LSP1- T-lymphoma cell line BW5147 to show that LSP1 interacts with F-actin and the cytoskeleton through residues downstream of amino acid residue 230. We then designed a novel cell-free cytoskeleton binding assay in which a set of GST-LSP1 fusion proteins are allowed to bind to the cytoskeleton in NP-40 soluble lysates of BW5147 cells and are recovered in the low-speed detergent insoluble pellet. Using this assay the cytoskeleton binding site of mouse LSP1 maps to the 300-330 interval. These results will allow the design of LSP1 mutants that do not bind to the cytoskeleton to determine the importance of LSP1 cytoskeleton binding for the diverse functions of LSP1.
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PMID:A cell-free binding assay maps the LSP1 cytoskeletal binding site to the COOH-terminal 30 amino acids. 1297 89

The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA) protein stabilizes beta-catenin by the novel mechanism of binding to the negative regulator, glycogen synthase kinase 3 (GSK-3), and depleting cytoplasmic GSK-3 levels. The two domains of LANA required for interaction with GSK-3 were further characterized. Evidence for similarity between the C-terminal LANA interaction domain and the axin GSK-3 interaction domain was obtained using GSK-3 and LANA mutants. GSK-3(F291L), which does not interact with axin, also failed to bind to LANA, and a mutation in the axin homology domain of LANA, L1132P, destroyed binding to GSK-3. The N-terminal LANA interaction domain was found to mediate interaction by acting as a substrate for GSK-3. GSK-3(R96A), a priming pocket mutant, did not bind to LANA, suggesting that LANA was a primed GSK-3 substrate. Phosphorylation of endogenous LANA precipitated from primary effusion lymphoma cells was inhibited by the GSK-3 inhibitor LiCl. GST-LANA(1-340) was phosphorylated by GSK-3, and mitogen-activated protein kinase (MAPK) and casein kinase I functioned as priming kinases in vitro. Mutation of consensus GSK-3 sites revealed that sites between LANA amino acids 219 and 268 were important for GSK-3 phosphorylation. Immunoprecipitation assays revealed that loss of GSK-3 phosphorylation of this N-terminal domain correlated with loss of GSK-3 interaction. Although LANA-associated GSK-3 actively phosphorylated LANA, GSK-3 coprecipitated with LANA was unable to phosphorylate an exogenous peptide substrate. LANA sequestration of GSK-3 may explain the ability of KSHV-infected cells to tolerate increased levels of nuclear GSK-3.
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PMID:Regulation of the interaction between glycogen synthase kinase 3 and the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen. 1605 35

Methotrexate is administered in high doses to treat childhood acute lymphoblastic leukemia and malignant lymphoma. Hepatotoxicity and bone marrow suppression often limit its use, however. The objective of this study was to determine the genetic polymorphisms associated with the hepatotoxicity and elimination of methotrexate. Genetic polymorphisms of glutathione S-transferase (GST) genes including GSTT1 positive/null, GSTM1 positive/null, and GSTP1 A313G, and genes for reduced folate carrier 1 G80A (RFC1 G80A), methylenetetrahydrofolate reductase C677T (MTHFR C677T), and breast cancer resistant protein C421A (BCRP C421A) were determined for 26 patients by the polymerase chain reaction (PCR) method or by direct sequencing. A high frequency of hepatotoxicity (P = 0.035) was observed for patients with GSTM1 positive and RFC1 AA(80), and serum concentrations of methotrexate 48 h after the start of infusion were higher for patients with the TT(677) genotype of MTHFR (P = 0.028). In conclusion, GSTM1 positive/null and RFC1 G80A polymorphisms could be predictors for hepatotoxicity, and the MTHFR C677T polymorphism is associated with elimination of methotrexate.
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PMID:Genetic polymorphisms associated with adverse events and elimination of methotrexate in childhood acute lymphoblastic leukemia and malignant lymphoma. 1718 May 79

Polymorphisms in detoxification enzymes of the glutathione S-transferase (GST) family have been associated with risk and prognosis of several cancer types. We studied deletions of GSTM1 and GSTT1, and the GSTP1 Ile(105)Val polymorphism in 89 patients with follicular lymphoma (FL). Patients with a GSTM1 or GSTT1 deletion had a significantly worse event-free survival, when compared with patients with undeleted genotype (p = 0.03 and p = 0.03, respectively). Outcome was even worse in patients with a double negative genotype, in comparison with patients with only one GST deletion or normal genotype (p = 0.01). In the multivariate analysis, the GSTM1/GSTT1 genotype tended to have a prognostic significance independent from the Follicular Lymphoma International Prognostic Index (FLIPI) score. In particular, GSTM1/T1 deletions identified patients with negative prognosis in the low (<3) FLIPI score group (p = 0.01). Larger prospective studies including homogeneously treated patients will be needed to confirm these results.
Leuk Lymphoma 2007 Mar
PMID:Glutathione-S-transferase genotypes influence prognosis in follicular non-Hodgkin's Lymphoma. 1745

Kaposi sarcoma-associated herpesvirus is associated with two lymphoproliferative disorders, primary effusion lymphoma (PEL) and Castleman disease. In PEL, Kaposi sarcoma-associated herpesvirus is present in a latent form expressing only few viral genes. Among them is a viral homologue of cellular interferon regulatory factors, vIRF-3. To study the role of vIRF-3 in PEL lymphomagenesis, we analyzed the interaction of vIRF-3 with cellular proteins. Using yeast two-hybrid screen, we detected the association between vIRF-3 and c-Myc suppressor, MM-1alpha. The vIRF-3 and MM-1alpha interaction was also demonstrated by glutathione S-transferase pulldown assay and coimmunoprecipitation of endogenous vIRF-3 and MM-1alpha in PEL-derived cell lines. Overexpression of vIRF-3 enhanced the c-Myc-dependent transcription of the gene cdk4. Addressing the molecular mechanism of the vIRF-3-mediated stimulation, we demonstrated that the association between MM-1alpha and c-Myc was inhibited by vIRF-3. Furthermore, the recruitment of vIRF-3 to the cdk4 promoter and the elevated levels of the histone H3 acetylation suggest the direct involvement of vIRF-3 in the activation of c-Myc-mediated transcription. These findings indicate that vIRF-3 can effectively stimulate c-Myc function in PEL cells and consequently contribute to de-regulation of B-cell growth and differentiation.
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PMID:Stimulation of c-Myc transcriptional activity by vIRF-3 of Kaposi sarcoma-associated herpesvirus. 1772 44

The Epstein-Barr and Kaposi's sarcoma gamma-herpesviruses (KSHVs) are associated with certain cancers, and encode B-cell leukemia/lymphoma 2 (BCL-2) homologs, BHRF-1 and KSHV BCL-2, respectively. Little is known, however, about the molecular interactions allowing viral BCL-2 homologs to mediate their anti-apoptotic function. Cellular anti-apoptotic proteins, such as BCL-2 and MCL-1, prevent death via selective interactions with pro-death BH3-only proteins. To investigate whether BHRF-1 and KSHV BCL-2 function similarly, we made recombinant BHRF-1 and KSHV BCL-2 proteins. We identified the individual binding patterns for BHRF-1 and KSHV BCL-2 to BH3 domains. These studies surprisingly showed that KSHV BCL-2 is more closely related to MCL-1 than to BCL-2, a result confirmed by sequence analysis. GST-BHRF-1 and GST-KSHV BCL-2 bound BH3-only family proteins from human cells. BHRF-1 protected mammalian cells from growth factor withdrawal, etoposide and adriamycin. We found that both BCL-2 and BHRF-1 sequestered pro-death BH3-only proteins under growth factor-deficient conditions. Finally, we tested the ability of a panel of BH3 peptides to inhibit BHRF-1 and KSHV BCL-2 function in a mitochondrial model of apoptosis. We found that each could be inhibited by the select group of BH3 peptides identified in our binding assay. Our studies define the biochemical interactions underlying BHRF-1 and KSHV BCL-2 anti-apoptotic function, and identify peptides that are prototypic inhibitors of this function.
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PMID:BH3 domains define selective inhibitory interactions with BHRF-1 and KSHV BCL-2. 1808 38

The mechanisms involved in regulating mammary cell turnover during the pregnancy-lactation cycle in dairy cows are unclear. The objective of present experiment was to describe expression of genes encoding proteins known to be involved in pathways regulating mammary cell proliferation, apoptosis, differentiation, cell survival, and tissue remodeling. Mammary gland biopsies were taken 7 times during the pregnancy-lactation cycle of 10 dairy cows, and samples were analyzed by immunohistochemistry and real-time PCR. Cell proliferation was greatest during the dry period and apoptosis was high in early dry period and early lactation. Based on Fas (tumor necrosis factor receptor superfamily member 6), Fas ligand, and caspase-3, caspase-8, and caspase-9 gene expression, no indication was found of a stage-dependent shift between the extrinsic and intrinsic pathways leading to apoptosis. Gene expression of microsomal glutathione S-transferase (mGST) did not vary significantly, whereas B-cell leukemia/lymphoma 2 (Bcl-2) and BCL2-associated X protein (Bax) gene expression was greatest during the dry period and early lactation and coincided with high cell turnover. Gene expression of early response genes c-Fos, c-Jun, and c-Myc correlated to neither rate of cell proliferation nor plasma concentration of insulin-like growth factor (IGF)-I and insulin. Gene expression of nuclear factor of kappa light chain gene enhancer in B-cells (NFkappaB) and NFkappaB inhibitor alpha was greatest in the periparturient period, and NFkappaB gene expression coincided with an anticipated need for cell survival factors. Expression of transforming growth factor beta (TGF-beta) receptor 1 and 2 mRNA was greatest in early lactation, whereas TGF-beta1 did not vary significant during the pregnancy-lactation cycle. Even though our results on the TGF-beta system did not comply with other studies, the gene expression pattern of the TGF-beta receptors indicates a role in regulating apoptosis in early lactation. Signal transducer and activator of transcription 5 (STAT5) gene expression was high in the periparturient period, which suggests a role for STAT5 in regulation of mammary cell proliferation and differentiation in dairy cows. Expression of tissue-plasminogen activator, plasminogen activator inhibitor-1, and IGF binding protein 5 genes was greatest in early lactation, suggesting a role for IGF binding protein 5 in coordinating regulation of apoptosis and tissue remodeling.
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PMID:Cellular mechanisms in regulating mammary cell turnover during lactation and dry period in dairy cows. 1848 54

Antioxidants are substances that fight against ROS (reactive oxygen species) and protect the cells from their damaging effects. Production of ROS during cellular metabolism is balanced by their removal by antioxidants. Any condition leading to increased levels of ROS results in oxidative stress, which promotes a large number of human diseases, including cancer. Therefore antioxidants may be regarded as potential anticarcinogens, as they may slow down or prevent development of cancer by reducing oxidative stress. Fruits and vegetables are rich source of antioxidants. Moreover, a number of phytochemicals present in medicinal plants are known to possess antioxidant activity. Therefore the aim of the present study was to investigate antioxidant activity of the aqueous extract of nuts of the medicinal plant Semecarpus anacardium in AKR mouse liver during the development of lymphoma. Antioxidant action was monitored by the activities of antioxidant enzymes catalase, superoxide dismutase and glutathione transferase. The effect of S. anacardium was also studied by observing the activity of LDH (lactate dehydrogenase), an enzyme of anaerobic metabolism. LDH activity serves as a tumour marker. The activities of antioxidant enzymes decreased gradually as lymphoma developed in mouse. However, LDH activity increased progressively. Administration of the aqueous extract of S. anacardium to lymphoma-transplanted mouse led to an increase in the activities of antioxidant enzymes, whereas LDH activity decreased significantly, indicating a decrease in carcinogenesis. The aqueous extract was found to be more effective than doxorubicin, a classical anticarcinogenic drug, with respect to its action on antioxidant enzymes and LDH in the liver of mice with developing lymphomas.
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PMID:Semecarpus anacardium nut extract promotes the antioxidant defence system and inhibits anaerobic metabolism during development of lymphoma. 1876 79


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