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)

Novel vitamin D3 derivatives, 26-homo-delta 22-1 alpha,25(S)-dihydroxyvitamin D3 and 26-homo-delta 22-1 alpha,25(R)-dihydroxyvitamin D3 were compared with the native hormone, 1,25-dihydroxyvitamin D3, and with other vitamin D3 derivatives, in inhibition of cell growth, induction of phenotypic differentiation, and c-myc mRNA reduction of HL-60 cells. The degree of inhibition in cell growth caused by 26-homo-delta 22-1 alpha,25(S)-(OH)2D3 was the greatest followed by 26-homo-delta 22-1 alpha,25(R)-(OH)2D3. The ability to reduce NBT was parallel to that to inhibit cellular proliferation. 26-homo-delta 22-1 alpha,25(S)-(OH)2D3, 26-homo-delta 22-1 alpha,25(R)-(OH)2D3, 24-homo-24-F2-1 alpha,25-(OH)2D3, and 1 alpha,24(R)-(OH)2-26-Cl-D3 were more active than 1 alpha,25-(OH)2D3 in the induction of OK-M1+ and OK-Mo-2+ HL-60 cells. Using two color flow cytometric analysis, the percentages of OK-M5(+)- and OK-DR(+)-HL-60 cells were 33% in the treatment with 26-homo-delta 22-1 alpha,25(S)-(OH)2D3 plus interferon-gamma (IFN-gamma) but 14% in the treatment with 1 alpha,25-(OH)2D3 plus IFN-gamma. 26-Homo-delta 22-1 alpha,25(S)-(OH)2D3 has an inhibitory effect on c-myc reduction in treated HL-60 cells. These results suggest that the novel vitamin D3 derivatives, 26-homo-delta 22-1 alpha,25(S)-(OH)2D3 and 26-homo-delta 22-1 alpha,25(R)-(OH)2D3, have preferential activity in inducing phenotypic differentiation and in inducing cell proliferation related c-myc mRNA activity.
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PMID:Novel vitamin D3 derivatives, 26-homo-delta 22-dehydro-1 alpha,25(S)-dihydroxyvitamin D3 and 26-homo-delta 22-dehydro-1 alpha,25(R)-dihydroxyvitamin D3: preferential activity in c-myc mRNA production and in induction of phenotypic differentiation of HL-60 cells. 240 90

Induction of hematopoietic differentiation in human promyelocytic leukemia cells (HL-60) by new synthetic drugs or natural products has recently been recognized as a new strategy in the identification and testing of potential cancer chemopreventive and/or chemotherapeutic agents. 2-(Allythio) pyrazine (2-AP) is a pyrazine derivative of allysulfide, which has been suggested to be a potential cancer chemopreventive agent in previous in vivo and in vitro experiments. In the present study, we have investigated the inducing effect of granulocytic differentiation in HL-60 cells by 2-AP. Treatment of HL-60 cells with various concentrations of 2-AP (1-100 microM) for 7 days showed the induction of granulocytic differentiation following both morphological examination and NBT (nitroblue tetrazolium) testing (up to 40 and 52%, respectively). The expressions of bcl-2 and c-myc were down-regulated during granulocytic differentiation of HL-60 cells (up to 40%). The immunoblots for G1 cyclins in the G1-S phase transition (cyclin D1 and E) showed a progressive decrease of their expressions in both concentration- and time-dependent manners (up to 30 and 50%, respectively). These results suggest that 2-AP could induce the differentiation of HL-60 cells and might have potent cancer chemoprevention and/or chemotherapy roles in human leukemias.
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PMID:Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by 2-(allylthio) pyrazine. 1050 71

To evaluate the effects of a novel 2-aminosteroid, 2-(4'-methyl-1'-piperazinyl)-3alpha-hydroxyl-5alpha-androstane-17-one (KH), on in vitro murine WEHI-3B leukemia cells, semisolid colony culture, MTT assay, morphological examination, NBT reduction, NSAE test and ACP assay were used to determine proliferation and differentiation. It was found that the growth of leukemia cells in colony and liquid cultures was inhibited by KH (10(-8)-10(-4) mol/l) after treatment for 7 days. The percentages of NBT and NSAE positive cells were 71.17 and 79.25%, respectively, after treatment with KH (10(-8)-10(-6) mol/l) for 5 days. The morphology of treated leukemia cells was identified to be macrophage-like and these cells acquired significant ACP activities. It was indicated that the ACP enzyme activities were increased as high as two and three times of the control, respectively, after treatment with 10(-8) or 10(-5) mol/l KH for 6 days. It was also indicated by DNA fragmentation in gel electrophoresis that WEHI-3B cells were induced toward apoptosis by KH (10(-8)-10(-4) mol/l) when checked at day 5. The c-myc mRNA expressions in WEHI-3B cells were decreased by 58.7% after treatment with KH (10(-8) mol/l) for 5 days. Therefore, it is first reported here that KH, a novel 2-aminosteroid, could suppress proliferation and induce differentiation of WEHI-3B leukemia cells. These differentiated cells were mature macrophage-like cells and showed characteristics of functional phagocytes acquired with acid phosphatase activity. The mechanisms underlying the above effects involved the apoptosis of WEHI-3B leukemia cells and the down-regulation of c-myc oncogene expression. It is also shown that the counts of immature granulocytes and monocytes were significantly decreased in both peripheral blood and bone marrow of BALB/c leukemia mice after KH was administrated per os for 7 consecutive days with four doses (5, 10, 15 or 20 mg/kg day), respectively. It is also observed that the enlarged spleens in leukemia mice were decreased when compared with the control.
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PMID:The effects and mechanisms of a novel 2-aminosteroid on murine WEHI-3B leukemia cells in vitro and in vivo. 1133 17

18:1/docosahexaenoic acid (DHA)-containing phosphatidylethanolamine (PE) enhanced cell differentiation and growth inhibition of HL-60 induced by dibutyryl cAMP (dbcAMP) in a dose-dependent manner. The combined treatment of 200 microM dbcAMP and 50 microM 18:1/DHA-PE increased the NBT reducing activity, which is as an indicator of cell differentiation, to more than 75% from 40% of cells treated with 200 microM dbcAMP alone. In HL-60 cells treated with 50 microM 18:1/DHA-PE and 200 microM dbcAMP for 24 h, the expression level of c-jun mRNA and c-Jun protein were remarkably elevated compared to cells treated with dbcAMP alone. In contrast, there was no difference in the expression levels of c-fos mRNA and c-Fos protein between the combination of 18:1/DHA-PE + dbcAMP or dbcAMP alone. On the other hand, the combine treatment of 18:1/DHA-PE and dbcAMP markedly reduced the expression level of c-myc oncogene during 48 h incubation. The decreases of c-myc mRNA by 18:1/DHA-PE and/or dbcAMP was correlated with growth inhibition effect. Thus, 18:1/DHA-PE might enhance dbcAMP-induced HL-60 cell differentiation and growth inhibition by regulation of c-jun and c-myc mRNA and their products.
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PMID:Docosahexaenoic acid-containing phosphatidylethanolamine enhances HL-60 cell differentiation by regulation of c-jun and c-myc expression. 1633 92

This study was aimed to investigate the enhancement of all-trans retinoic acid-induced HL-60 leukemia cell differentiation by human umbilical cord mesenchymal stem cells (hucMSC). The HL-60 cells were divided into 4 groups: control group (HL-60 cells treated without ATRA), hucMSC group (HL-60 cells co-cultured with hucMSCs), ATRA group (HL-60 cells treated with ATRA) and ATRA + hucMSC group (HL-60 cells treated with ATRA and co-cultured with hucMSCs). The proliferations of control group and hucMSC group were compared by Cell Counting Kit-8 (CCK8). The morphology of HL-60 cells and NBT positive rate in 4 groups were observed and compared by means of microscopy, the c-myc expression of HL-60 cells in different groups was evaluated by real-time PCR, and the CD11b expression on HL-60 cells in different groups were detected by flow cytometry. The results showed that in the co-culturing system, hucMSCs could inhibit the proliferation of HL-60 (hucMSC:HL-60 is 1:1, 48 hours p < 0.05, 72 hours p < 0.01; hucMSC:HL-60 is 1:5, 72 hours p < 0.05). In condition of stimulation with 2 micromol/L ATRA, the neutrophil like HL-60 cells and NBT positive rate in ATRA + hucMSC group were higher than those in ATRA group (p < 0.05). The c-myc expression of HL-60 cells in ATRA + hucMSC group was lower than that in ATRA group (p < 0.05). Furthermore, HL-60 cells in ATRA + hucMSC group had stronger CD11b expression than ATRA group (48 hours p < 0.05, 72 hours p < 0.01). It is concluded that hucMSC not only can inhibit the proliferation of HL-60 cells, but also can enhance the differentiation effect of HL-60 cells induced by ATRA.
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PMID:[Enhancement of all-trans retinoic acid induced HL-60 leukemia cell differentiation by human umbilical cord mesenchymal stem cells]. 2072 92

Momordica charantia (bitter gourd) has been used in the traditional system of medicine for the treatment of various diseases. Anticancer activity of M. charantia extracts has been demonstrated by numerous in vitro and in vivo studies. In the present study, we investigated the differentiation inducing potential of fractionated M. charantia seed extracts in human myeloid HL60 cells. We found that the HL60 cells treated with the fractionated seed extracts differentiated into granulocytic lineage as characterized by NBT staining, CD11b expression, and specific esterase activity. The differentiation inducing principle was found to be heat-stable, and organic in nature. The differentiation was accompanied by a downregulation of c-myc transcript, indicating the involvement of c-myc pathway, at least in part, in differentiation. Taken together these results indicate that fractionated extracts of M. charantia seeds possess differentiation inducing activity and therefore can be evaluated for their potential use in differentiation therapy for leukemia in combination with other inducers of differentiation.
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PMID:Antileukemic Potential of Momordica charantia Seed Extracts on Human Myeloid Leukemic HL60 Cells. 2265 56