Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Determinations were made of glyoxalase I and glyoxalase II acitivity in the liver of mice (BDF1 and DBA2 strains) bearing sarcoma 180 and L1210 leukemia in ascites form. A progressive decrease in the both glyoxalase I and glyoxalase II activities to about 40--60% of that of the control groups was observed within the developing period 8--9 days. Test results are interpreted in the light of the postulated role of this enzyme system in cell division and in the tumor development process.
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PMID:Further studies on liver glyoxalase I and glyoxalase II. Activity in mice bearing sarcoma 180 and L1210 leukemia. 69 5

Diethyl esters of the glutathione S-conjugate S-p-bromobenzylglutathione, an inhibitor of glyoxalase I, and S-p-nitrobenzoxycarbonylglutathione, an inhibitor of glyoxalase II, induced growth arrest and toxicity in human leukaemia 60 cells in culture. The median growth inhibitory concentration IC50 values were 8.3 microM (95% C.I. 7.0-9.9 microM) for S-p-bromobenzylglutathione diethyl ester and 56 microM (95% C.I. 36-86 microM) for p-nitrobenzoxycarbonylglutathione. Monoethyl ester and unesterified derivatives were inactive. The diethyl ester derivatives were also toxic to mature human neutrophils under the same culture conditions where the respective median toxic concentration IC50 values were 39.7 (95% C.I. 35.4-44.5 microM) and 127 (95% C.I. 123-132 microM) microM. Diester derivatives may be of future interest in studying the cytotoxicity of glutathione S-conjugates and for the development of cytotoxic anti-tumour agents.
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PMID:Inhibition of proliferation of human leukaemia 60 cells by diethyl esters of glyoxalase inhibitors in vitro. 147

Human promyelocytic leukaemia HL60 cells were incubated with the glyoxalase intermediate S-D-lactoylglutathione in culture. The effects on cell proliferation, maturation, viability and cell cycle were investigated. When HL60 cells (5 x 10(4)/ml) were incubated with 50-500 microM S-D-lactoylglutathione for two days, the rate of cell proliferation was decreased. This effect was maximal at 500 microM S-D-lactoylglutathione where the cell proliferation rate was only 16% of control levels. There was a concomitant decrease in cell viability but little differentiation. During the first day of treatment, there was a significant decrease in the percentage of cells in the G2-M phase of the cell cycle with a concomitant increase in the G0-G1 phase. In contrast, when HL60 cells were incubated with 1.0-1.5 mM S-D-lactoylglutathione, the inhibition of cell proliferation was progressively lifted, with a concomitant increase in the percentage of differentiated cells (27% differentiation with 1.5 mM S-D-lactoylglutathione). The activities of glyoxalase II and gamma-glutamyl transpeptidase were increased in these cells. S-D-Lactoylglutathione slowly entered the HL60 cells and was consumed over the period when changes in cell cycle distribution, growth arrest and decrease in cell viability were observed. The mechanism of inhibition of proliferation of HL60 promyelocytes by S-D-lactoylglutathione is unknown but it may be related to the ability of S-D-lactoylglutathione to stimulate the assembly of microtubules.
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PMID:Inhibition of proliferation of human promyelocytic leukaemia HL60 cells by S-D-lactoylglutathione in vitro. 290 55

The glyoxalase system of human promyelocytic leukaemia HL60 cells was substantially modified during differentiation to neutrophils. The activity of glyoxalase I was decreased and the activity of glyoxalase II was markedly increased relative to the level in control HL60 promyelocytes. There was a decrease in the apparent maximum velocity, Vmax, of glyoxalase I, and an increase in the Vmax of glyoxalase II. The apparent Michaelis constants for both enzymes remained unchanged. The flux of intermediates metabolised via the glyoxalase system increased during differentiation, as judged by the formation of D-lactic acid, whereas the percentage of glucotriose metabolised via the glyoxalase system remained unchanged. The cellular concentrations of the glyoxalase substrates, methylglyoxal and S-D-lactoylglutathione, were markedly decreased during differentiation. The maturation of HL60 promyelocytes is associated with an increased ability to metabolise S-D-lactoylglutathione by glyoxalase II and a concomitant decrease in the mean intracellular concentrations of S-D-lactoylglutathione and methylglyoxal. The maintenance of a high concentration of S-D-lactoylglutathione in HL60 promyelocytes may be related to the status of the microtubular cytoskeleton, since S-D-lactoylglutathione potentiates the GTP-promoted assembly of microtubules.
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PMID:Modification of the glyoxalase system in human HL60 promyelocytic leukaemia cells during differentiation to neutrophils in vitro. 316 82

The activities of glyoxalase I and glyoxalase II were determined in human promyelocytic leukaemia HL60 and erythroleukaemia K562 cells in culture. The activity of glyoxalase I is ca 10-20 times greater than the activity of glyoxalase II under assay conditions. When HL60 and K562 cell lines were incubated with N-methylformamide and 8-carbamoyl-3-methylimidazo-[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (CCRG 81045), substantial changes in the glyoxalase activities were induced. With HL60 cells, treatment with N-methylformamide and CCRG 81045, both of which induce functional differentiation of this cell line, there is a dose-dependent decrease in glyoxalase I activity and a concomitant dose-dependent increase in glyoxalase II activity, both of which are directly proportional to the number of differentiated cells. With K562 cells, N-methylformamide and CCRG 81045 induce an increase in both glyoxalase I and glyoxalase II activities, although only CCRG 81045 induces the appearance of haemoglobin producing cells. N-Methylformamide and CCRG 81045 do not activate or inhibit the activities of glyoxalase I and glyoxalase II from HL60 and K562 cells when studied in cell-free systems. The changes in the glyoxalase activities of HL60 and K562 cells during the incubations therefore appear to be due to alteration in the synthesis and/or regulatory modification of the glyoxalase enzymes induced by N-methylformamide and CCRG 81045. Despite the apparent disparity of the effect of differentiation on the glyoxalase system in the two cell lines, in both cases the glyoxalase I/glyoxalase II activity ratio decreases with the appearance of differentiated cells. Since glyoxalase II catalyses the rate-determining step in the glyoxalase system, this suggests that immature cells have an impaired capacity to metabolise S-D-lactoylglutathione.
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PMID:Glyoxalase activity during differentiation of human leukaemia cells in vitro. 348 Apr 3

It has been reported that many malignant human tissues, including breast, colon, and lung cancers, may show an elevated expression of glyoxalase I (GLO I). GLO I catalyzes the reaction to transform hemimercaptal, a compound formed from methylglyoxal (MG) and reduced glutathione, into S-D-lactoylglutathione, which is then converted to D-lactic acid by glyoxalase II. GLO I inhibitors are expected to be useful for inhibiting tumorigenesis through the accumulation of apoptosis-inducible MG in tumor cells. Here, we investigated the anti-proliferative activity of eight kinds of isoflavone isolated from Erythrina poeppigiana against the growth of HL-60 human leukemia cells from the viewpoint of GLO I inhibition. Of the compounds tested, the diprenyl isoflavone, isolupalbigenin, was shown to exhibit the highest anti-proliferative activity against HL-60 cells. Upon the treatment of HL-60 cells with isolupalbigenin, MG was significantly accumulated in the culture medium, and the caspase 3 activity of the cell lysate was elevated in a time-dependent manner. Thus, it is suggested that isolupalbigenin inhibits the enzyme GLO I, resulting in MG accumulation in the medium, and leading to cell apoptosis. Isolupalbigenin, with two prenyl groups in its A- and B-rings, might be expected to become a potent leading compound for the development of anticancer agents.
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PMID:Inhibitory Effect of Isoflavones from Erythrina poeppigiana on the Growth of HL-60 Human Leukemia Cells through Inhibition of Glyoxalase I. 2659 64