Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02003 (NBT)
 1,323 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Natural or recombinant human tumor necrosis factor (TNF) induced NBT-reducing activity of ML-1 cells in a dose-dependent manner. Interferon-gamma (IFN-gamma) induced NBT-reducing activity only marginally. However, when IFN-gamma was combined with TNF, induction of NBT-reducing activity was remarkably increased. IFN-alpha or -beta had almost no effect on the induction of NBT-reducing activity of ML-1 cells, either alone or in combination with TNF. Treatment with both TNF and IFN-gamma synergistically enhanced morphological changes, growth inhibition and activity of Fc receptors, and NBT reduction in ML-1 cells, but not phagocytic activity. The TNF treated cells were classified as macrophage-like by morphology, and by lineage-specific alpha-naphthyl acetate esterase stain. The results indicate that combinations of TNF and IFN-gamma act synergistically in the induction of differentiation of human myeloblastic ML-1 cells.
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PMID:Synergism of tumor necrosis factor and interferon-gamma in induction of differentiation of human myeloblastic leukemic ML-1 cells. 310 15

The individual roles of two types of TNF receptors (55 kDa and 75 kDa) in induction of differentiation of human myeloblastic leukemia ML-1 cells were investigated using three monoclonal antibodies. The antibody htr-9, which recognizes the 55 kDa receptor, induced differentiation of ML-1 cells. Utr-1, which recognizes the 75 kDa receptor, blocked 125I-TNF binding by about 80% and inhibited by about 80% the TNF-induced NBT reducing activity. Htr-5 recognizes the 55 kDa receptor, blocked 125I-TNF binding by about 20% and inhibited by about 60% the TNF-induced NBT reducing activity. The data suggest that either of the two TNF receptors alone can mediate signals for the differentiation of ML-1 cells, and that simultaneous stimulation of both receptors will induce differentiation more effectively.
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PMID:Roles of two tumor necrosis factor receptors in induction of differentiation of ML-1 cells. 839 78

The effects of all-trans retinoic acid (ATRA), either alone or in combination with GM-CSF, on the induction of differentiation of a human myeloblastic leukemia cell line, ML-1, were investigated. ATRA alone caused only slight induction of NBT-reducing activity even at a high concentration (10(-7) M), but when combined with GM-CSF, it led to remarkable increase in the induction of NBT-reducing activity. Synergistic effect of both agents was also observed on morphological changes and the inhibition of cell proliferation. When ATRA or GM-CSF was used alone, neither parameter was changed substantially for long periods of up to 9 days. However, the combination of both agents induced remarkable morphological changes with segmented nuclei and also suppressed DNA-synthesizing activity.
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PMID:Retinoic acid combined with GM-CSF induces morphological changes with segmented nuclei in human myeloblastic leukemia ML-1 cells. 921 50

Boswellic acid acetate (BC-4), a compound isolated from the herb Boswellia carterii Birdw., can induce differentiation and apoptosis of leukemia cells. Based on cell morphology and NBT reduction, BC-4 induced monocytic differentiation of myeloid leukemia HL-60, U937 and ML-1 cells at a dose under 12.5 microg/ml (24.2 microM). BC-4 was a potent inducer, with 90% of the cells showing morphologic changes and 80-90% of the cells showing NBT reduction. Specific and non-specific esterase were also increased by BC-4. Based on benzidine staining assay, BC-4 failed to induce erythroid leukemia DS-19 and K562 cells differentiation. In contrast to its selective differentiation effect, BC-4 strongly inhibited growth of all cell lines tested. The growth inhibition effect was dose- and time-dependent. In HL-60 cells, 20 microg/ml (38.8 microM) of BC-4 decreased viable cell number by 60% at 24 h, whereas at 3 days there was virtually no viable cells. Morphologic and DNA fragmentation analysis proved that BC-4 induced cell apoptosis. The dual apoptotic and differentiation effects of BC-4 suggest that it may be a powerful agent in the treatment of leukemia.
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PMID:Boswellic acid acetate induces differentiation and apoptosis in leukemia cell lines. 993 34

Various inhibitors of protein kinases regulate the growth and differentiation of human leukemic cell lines. The pyridinyl imidazole inhibitor SB203580 has been widely used to elucidate the role of p38 kinase in a wide array of biological systems. In the present investigation, we found that SB203580 effectively induced the granulocytic differentiation of human promyelocytic HL-60 cells. In addition to morphological differentiation, it also induced NBT-reduction, lysozyme activity and growth-inhibition. It also induced the differentiation of human myeloid leukemia HT93 and ML-1 cells, but not of other cell lines, such as NB4, U937, THP-1, K562 and HEL. This differentiation was not associated with the inhibition of p38 kinase activity, but was closely associated with the activation of extracellular signal-regulated kinase. These results demonstrate a new activity for this drug.
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PMID:Pyridinyl imidazole inhibitor SB203580 activates p44/42 mitogen-activated protein kinase and induces the differentiation of human myeloid leukemia cells. 1148 75

We reported previously that treatment of human myeloblastic leukemia ML-1 cells with all-trans retinoic acid (ATRA) in combination with GM-CSF enhances the granulocytic differentiation, which is induced only slightly by ATRA alone. To investigate the mechanism underlying this differentiation and the synergistic effect of ATRA and GM-CSF, we used cDNA microarray to examine gene expression profiles of ML-1 cells treated with ATRA and/or GM-CSF. We identified 22 up-regulated genes in ML-1 cells treated with both reagents and examined the expression of these genes in cells treated with ATRA and/or GM-CSF by Northern blot analysis. Comparison of cells treated with both reagents and cells treated with ATRA or GM-CSF alone revealed that expression of nine of the 19 genes was induced synergistically by combined treatment with ATRA and GM-CSF. Expression of most of these genes was increased only slightly by ATRA alone, and this induction was enhanced by the addition of GM-CSF. These results indicate that GM-CSF enhances ATRA-induced gene expression. Moreover, studies with inhibitors of signaling molecules suggested that activation of JAK2 is associated with the synergistic induction of several genes by ATRA and GM-CSF. JAK2 inhibitor suppressed induction of NBT-reducing activity in ML-1 cells treated with both reagents. It is likely that the enhancer effect of GM-CSF on ATRA-induced gene expression leads to the differentiation induced synergistically by ATRA combined with GM-CSF. Further studies of the mechanism underlying this effect may identify better approaches for the treatment of RA-insensitive leukemia.
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PMID:Granulocyte macrophage colony-stimulating factor enhances retinoic acid-induced gene expression. 1688 1