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)

Phorbol, the unesterified parent alcohol of the skin promoter TPA, was administered i.p., twice weekly, throughout the lifetime of mice of 7 inbred strains: males and females of AKR/J, C3Heb and BALB/c, and females of SJL/J, DBA/2, SWR and C57BL. A striking difference in strain response was observed, with a pronounced leukaemogenic effect in SWR, a signficiant shortening of the latent period for spontaneous reticulum cell sarcomas (RCNB) in SJL/J, and no demonstrable effect in the other strains. When mice of 3 of the above-mentioned strains (SWR, SJL/J and AKR/J) were thymectomized prior to the beginning of phorbol treatment, different patterns of response were again observed. Thymectomy did not influence the leukaemia incidence in SWR mice, slightly inhibited RCNB development in SJL/J mice and converted phorbol into a leukaemogenic agent for AKR/J mice.
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PMID:Leukaemogenic action of phorbol in intact and thymectomized mice of different strains. 79 8

In this report, we elucidate the role of Na(+)-K+ pump in the regulation of polyamine spermidine (Spd) transport in murine leukemia (L 1210) cells in culture. Ouabain, known to bind extracellularly to the alpha-subunit of the Na(+)-K+ pump, inhibits the pump activity. The L 1210 cells were found to possess ouabain binding sites at 7.5 fmol/10(6) cells. Ouabain significantly inhibited the Spd uptake in a dose-dependent manner. The maximum inhibition of Spd uptake by ouabain was observed beyond 200 microM. Spd transport was inversely correlated with the [3H]ouabain binding to L 1210 cells: an increase in the saturation of ouabain binding to L 1210 cells resulted in a decrease of the Spd uptake process. Treatment of L 1210 cells with protein kinase C activator phorbol esters increased the Spd transport and, also, ouabain-sensitive 86Rb+ uptake, a measure of the activity of the Na(+)-K+ pump. H-7, a protein kinase C inhibitor, significantly inhibited the ouabain-sensitive 86Rb+ uptake by L 1210 cells. Phorbol esters stimulated the level, but not the rate, of 22Na+ influx. Addition of H-7 to L 1210 cells inhibited the 22Na+ influx process. A concomitant phorbol ester-induced increase in 22Na+ influx, [14C]Spd uptake, together with the functioning of Na(+)-K+ pump, indicates the role of the "Na+ cycle" in the regulation of the polyamine transport process.
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PMID:Phorbol esters augment polyamine transport by influencing Na(+)-K+ pump in murine leukemia cells. 131 10

The reovirus receptor on mammalian cells has not been fully characterized and controversy exists over the nature of this receptor. We report here that the expression of this receptor is dependent on the differentiation status of a human promyelocytic leukaemia cell line (HL60). Phorbol treatment of HL60 cells for 24 h, at a concentration range of 160 nM down to 1 nM, led to differentiation of these cells towards monocytes and a loss of approximately 80% of their ability to bind reovirus in a fluorescence assay. These cells also lost their susceptibility to T1 and T3 reovirus infection. DMSO treatment for 24 h at a concentration of 1.25% (v/v) led to differentiation towards granulocytes. This was accompanied by an increase of approximately 15% in binding of reovirus to these cells. After being infected by T1 or T3 reovirus, the granulocytes produced higher titres of progeny virus than did untreated HL60 cells. Similar differences were noted when virus binding to HL60 cells was assayed using radiolabelled reovirus. These effects were not detected when murine L fibroblasts were treated with DMSO or phorbol. ATCC-derived murine R1.1 cells did not bind reovirus. Competition data indicated that there may be two reovirus receptors on HL60 cells, and that T1 can bind to only one receptor whereas T3 can bind to both receptors. Our data also suggested that the beta-adrenergic receptor was unlikely to act as the reovirus receptor on HL60 cells.
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PMID:Regulation of expression of the reovirus receptor on differentiated HL60 cells. 164 37

Phorbol-12-myristate 13-acetate (PMA), a stimulator of protein kinase C, dramatically decreased topoisomerase II-reactive drug-induced DNA cleavage in HL-60 human leukemia cells. The effect of staurosporine, an inhibitor of protein kinase C, on drug-induced, topoisomerase II-mediated DNA cleavage was quantified in the same cells. Staurosporine decreased the magnitude of 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA)- and etoposide-induced DNA cleavage in a dose- and time-dependent fashion. Measurement of several parameters of cell proliferation revealed no clear and uniform correlation between staurosporine's inhibition of these parameters and its effects on drug-induced DNA cleavage. A direct comparison with PMA's effects on drug-induced DNA cleavage showed that whereas PMA's inhibition of etoposide-induced cleavage was much greater than its inhibition of m-AMSA-induced cleavage, the magnitude of staurosporine's effect on the cleavage produced by the two topoisomerase II-reactive drugs was similar. Thus, although PMA stimulates protein kinase C and staurosporine inhibits this enzyme, it is unlikely that the actions of either on topoisomerase II-reactive, drug-induced DNA cleavage are mediated directly via protein kinase C. Furthermore, it is likely that the mechanisms by which PMA and staurosporine inhibit topoisomerase II-reactive drug-induced cleavage are different.
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PMID:The effect of staurosporine on drug-induced, topoisomerase II-mediated DNA cleavage in human leukemia cells. 166 Mar 53

Phorbol myristate acetate (PMA) but not its inactive analogue phorbol didecanoate modulated the release of [3H] serotonin by rat basophilic leukemia (RBL) cells stimulated by antigen-IgE complexes. Concanavalin A or the calcium ionophore ionomycin, suggesting that protein kinase C (PKC) was involved in the exocytosis process. The PKC inhibitor sphingosine markedly inhibited release. When the PKC content of RBL cells was diminished by a prior 24 h-exposure (long-term PMA-treated cells) to 50 or 100 ng/ml PMA, the release induced by the three secretagogues was also strongly inhibited. Since cell activation by PMA in different cell systems is accompanied by PKC translocation from cytosol to membrane, we studied the location of PKC in resting cells and its translocation by a 5 min-exposure to 100 ng/ml PMA. PKC was cytosolic in long-term PMA-treated and control RBL cells and its translocation occurred regardless of the total PKC cell content, showing a possible correlation between the level of functional PKC (susceptible to be translocated) and exocytosis. Taken together, these data suggest that PKC is involved in the controlling of exocytosis by different secretagogues.
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PMID:Rat basophilic leukemia cells: protein kinase C and secretion. 193 87

Rat basophilic leukemia (RBL-2H3) cells serve as a model to examine the role of external and internal free Ca2+ concentration [Ca2+]i, following ionomycin induced stimulation of leukotriene C4 (LTC4) formation. Brief exposure of RBL cells to Ca(2+)-free medium abolished the effect of ionomycin on elevation of [Ca2+]i (monitored by Quin-2/AM) and on stimulation of LTC4 production. In Ca(2+)-rich medium (1.8 mM) however there was a large increase in both parameters. We showed recently (Her et al., 1990) that hydrocortisone (HC) and dexamethasone markedly suppressed the elevated [Ca2+]i induced by antigen. Following HC pretreatment, there was a modest (35%) suppression of [Ca2+]i elevation induced by submaximal (0.1 microM) as well as maximal (1 microM) doses of ionomycin (nevertheless, 8 fold increase above basal level was still observed), LTC4 formation, however, was only inhibited (47%) by HC when induced by submaximal dose of ionomycin, but not that induced by higher doses of ionomycin. Phorbol ester (TPA) abolished elevation of [Ca2+]i induced by antigen. Short treatment with TPA had a modest inhibitory (28%) effect on elevation of [Ca2+]i and on LTC4 formation (23%) induced by ionomycin. It is proposed that high [Ca2+]i, possibly originated mainly from extracellular source, is essential for induction of LTC4 formation.
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PMID:The role of external and internal free Ca2+ concentration on ionomycin induced leukotriene C4 formation in rat basophilic leukemia cells. 195 35

Phorbol 12,13-dibutyrate (PDBu) enhances 5'-(N-ethylcarboxamido)-adenosine (NECA) stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production in the human T-cell leukemia line, Jurkat. Addition of the Ca2+ ionophore A23187 lowered the EC50 value for PDBu from 49 to 7.1 nM. In binding experiments, where intact cells were incubated with [3H]PDBu at 37 degrees C, addition of A23187 increased the number of binding sites for the phorbol ester. Pretreatment of cells with A23187 was not sufficient to increase [3H]PDBu binding; A23187 had to be combined with phorbol ester in order to enhance [3H]PDBu binding. PDBu treatment translocated protein kinase from the cytosol to the membrane. This effect of the phorbol ester could be enhanced with A23187 whereas A23187 per se had no effect on protein kinase C distribution. From these data it is concluded that the synergism between A23187 and PDBu, monitored as enhancement of NECA-stimulated cAMP accumulation and increase in [3H]PDBu binding, is paralleled by translocation of the enzyme to the particulate fraction of the cells. The finding that cells where the cellular content of protein kinase C had been translocated to the membrane compartment bound more [3H]PDBu than control cells also suggests that [3H]PDBu binding to intact cells reflects the amount of membrane bound-, rather than the total cellular-enzyme content.
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PMID:Synergism between phorbol ester and the Ca2+ ionophore A23187 on protein kinase C translocation, [3H]PDBu binding and adenosine A2-receptor activation in Jurkat cells. 216 37

We examined the effects of phorbol ester treatment on topoisomerase II-mediated events in two human leukemia cell lines with different proclivities toward phorbol ester-induced monocytoid differentiation. HL-60 is the parent line that will terminally differentiate; 1E3 is a derived line that will not terminally differentiate. Within 24 h of phorbol ester treatment, etoposide-induced, topoisomerase II-mediated DNA cleavage declined 10-fold, whereas 4'-(9-acridinylamino)-methanesulfon-m-anisidide- induced DNA cleavage declined 3-fold in HL-60. In phorbol-treated 1E3, etoposide-induced DNA cleavage declined only 2-fold, whereas 4'-(9-acridinylamino)methanesulfon-m-anisidide-induced cleavage was barely affected. There was a 2- to 3-fold decline in topoisomerase II activity within the nuclear extracts from phorbol-treated HL-60 cells but not from phorbol-treated 1E3 cells. Immunoblotting experiments with anti-topoisomerase II antibodies indicated that phorbol treatment produced a structural change in the immunoreactive topiosomerase II in HL-60 nuclear extracts but produced no change in 1E3 topoisomerase II. Phorbol ester treatment also produced a decline in the level of topoisomerase II gene expression in HL-60 but not in 1E3 cells. By contrast, the cytotoxicity of etoposide in both lines was decreased following phorbol treatment. Thus, phorbols may uncouple the mechanisms linking drug-induced, topoisomerase II-DNA cleavable complex stabilization with drug-induced cytotoxicity, particularly in 1E3.
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PMID:Phorbol ester effects on topoisomerase II activity and gene expression in HL-60 human leukemia cells with different proclivities toward monocytoid differentiation. 217 56

The growth inhibitory effect of tumour promoters on human leukaemia and lung cancer cell lines was examined using the [3-(4,5 dimethylthiazol)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. The four cell lines used were the K562 human leukaemia cell line, its adriamycin (ADM)-resistant subline (K562/ADM), which shows the mdr phenotype, PC-9 (a human lung adenocarcinoma cell line) and its cisplatin (CDDP)-resistant subline (PC-9/CDDP), which does not show the mdr phenotype. Phorbol 12-tetradecanoate-13-acetate (TPA) and the TPA-type tumour promoters, aplysiatoxin and debromoaplysiatoxin, inhibited the growth of the two parental cell lines, K562 and PC-9. The non-TPA-type tumour promoter, okadaic acid, also inhibited the growth of the two parental cell lines in a dose-dependent manner. TPA-type and okadaic acid inhibited the growth of K562/ADM more weakly than that of K562, and showed no growth inhibition in PC-9/CDDP. Anhydrodebromoaplysiatoxin, an inactive derivative of the TPA-type tumour promoter, could suppress the growth of K562 and K562/ADM only at high concentration (more than 50 pM) and it showed similar growth inhibitory effects on the two cell lines. Okadaic acid tetramethyl ether, the inactive form of the non-TPA-type tumour promoter did not inhibit the growth of any of the cell lines. The growth inhibitory effect of these compounds was well correlated with their tumour-promoting activity. A study of the accumulation of okadaic acid revealed that the amount of 3H-okadaic acid in K562/ADM and PC-9/CDDP was similar to that in their parental cells indicating that cross-resistance to this tumour promoter in the drug-resistant cell lines is not due to a difference in the amount of drug accumulated in sensitive and resistant cells. These results suggest the presence of another common mechanism for resistance to ADM and CDDP as well as to TPA- or non-TPA-type tumour promoters.
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PMID:Cross-resistance to tumour promoters in human cancer cell lines resistant to adriamycin or cisplatin. 220 49

Phorbol ester-induced differentiation of human B-chronic lymphocytic leukaemic cells was found to be preceded by a rapid transient induction in expression of the c-jun proto-oncogene, which paralleled that of c-fos. Induced expression of c-myc but not of c-fos/c-jun proto-oncogenes was markedly higher in a proliferating variant leukaemic cell population compared with that seen in typical lymphocytic leukaemia cells. These data suggest that the c-fos/c-jun nuclear oncogenes play a role in induced differentiation, whilst c-myc is more important in the proliferative response of B lymphocytes.
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PMID:Patterns of nuclear proto-oncogene expression during induced differentiation and proliferation of human B chronic lymphocytic leukaemia cells. 231 71


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