Increased 14-3-3ζ Expression in the Multidrug-Resistant Leukemia Cell Line HL-60/VCR as Compared to the Parental Line Mediates Cell Growth and Apoptosis in Part through Modification of Gene Expression

2014 ◽  
Vol 132 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Rong Liang ◽  
Xie-Qun Chen ◽  
Qin-Xian Bai ◽  
Zhe Wang ◽  
Tao Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Growth ◽  
Cell Line ◽  
Leukemia Cell ◽  
Multidrug Resistant ◽  
Leukemia Cell Line ◽  
Parental Line

scholarly journals Comparative cellular pharmacology of daunorubicin and idarubicin in human multidrug-resistant leukemia cells

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3267-3273 ◽  
Author(s):  
E Berman ◽  
M McBride
Keyword(s):  
Growth Inhibition ◽  
Cell Line ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Fold Increase ◽  
Multidrug Resistant ◽  
Fresh Medium ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Cellular Pharmacology

Abstract We examined the effect of daunorubicin (DNR), the new anthracycline derivative idarubicin (IDR), and verapamil on two leukemia cell lines that displayed the multidrug resistant (MDR) phenotype and used laser flow cytometry to quantitate intracellular anthracycline content. The vinblastine-resistant human lymphoblastic leukemia cell line CEM-VBL demonstrated minimal DNR uptake; simultaneous incubation with verapamil and DNR increased intracellular DNR uptake fourfold. IDR uptake was 10 times more rapid in these cells and simultaneous incubation with IDR and verapamil resulted in only a 1.2-fold increase of intracellular IDR. Similar results were observed in the vincristine-resistant human myeloid leukemia cell line HL-60/RV+. Intracellular retention of DNR and IDR was also measured in each cell line. In CEM-BVL cells, 38% of the original DNR concentration remained after a 2-hour resuspension in fresh medium compared with 71% of the original IDR concentration. In HL- 60/RV+ cells, 36% of the DNR concentration remained compared with 51% of the IDR concentration. After incubation of CEM-VBL and HL-60/RV+ cells with DNR for 1 hour followed by resuspension in fresh medium plus verapamil, intracellular DNA retention increased 5- and 5.2-fold, respectively. However, incubation of these cells for 1 hour with IDR followed by resuspension in fresh medium plus verapamil resulted in only a 1.6- and 2.4-fold increase in intracellular IDR retention. Lastly, clonogenic experiments were performed to correlate intracellular anthracycline content with cytotoxicity. DNR alone had a minimal effect on the clonogenic growth of CEM-VBL cells, whereas the combination of DNR plus verapamil resulted in approximately 80% growth inhibition. However, incubation of these cells with IDR alone resulted in greater than 95% growth inhibition. These results suggest that IDR may be more effective than DNR in leukemia cells that display the MDR phenotype.

scholarly journals Differing responses of globin and glycophorin gene expression to hemin in the human leukemia cell line K562

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 738-746 ◽  
Author(s):  
BL Tonkonow ◽  
R Hoffman ◽  
D Burger ◽  
JT Elder ◽  
EM Mazur ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Globin Gene ◽  
Leukemia Cell ◽  
K562 Cells ◽  
Leukemia Cell Line ◽  
Human Leukemia ◽  
Globin Mrna ◽  
Human Leukemia Cell Line ◽  
Globin Gene Expression

Abstract The human leukemia cell line, K562, produces embryonic and fetal hemoglobins and glycophorin A, proteins normally associated only with erythroid cells. Hemoglobin accumulation is enhanced by exposure of the cells to 0.05 mM hemin. We have examined K562 cells before and after exposure to hemin to determine whether expression of these erythroid proteins was shared by all cells or confined to specific subpopulations. Globin gene expression was examined by quantitation of globin mRNA sequences, using a 3H-globin cDNA molecular hybridization probe. Constitutive cells produced globin mRNA, the content of which was increased 3–4-fold by hemin. Cell-to-cell distribution of globin mRNA was determined by in situ hybridization of 3H-globin cDNA to constitutive and hemin-treated K562 cells. Virtually all cells in the culture exhibited grain counts above background, indicating globin gene expression by all cells, rather than a confined subpopulation. Virtually all hemin-treated cells had 3–5-fold higher grain counts, indicating uniformly increased globin gene expression. The glycophorin content of K562 cells was estimated by fluorescence-activated cell sorting (FACS) of cells labeled with fluorescein-labeled antiglycophorin antiserum. The vast majority of constitutive cells contained glycophorin, but exhibited to apparent increase in glycophorin accumulation after hemin exposure. Thus, glycophorin and globin genes exhibited differential responses to hemin. These differences could reflect normal differences in the patterns of specialized gene expression in stem cells. Alternatively, different aberrations of gene expression could be occurring in response to the determinants of the neoplastic properties of K562.

2′,5′-Oligoadenylate-Antisense Chimeras Cause RNase L to Selectively Degrade bcr/abl mRNA in Chronic Myelogenous Leukemia Cells

Blood ◽  
1998 ◽  
Vol 92 (11) ◽  
pp. 4336-4343 ◽  
Author(s):  
Avudaiappan Maran ◽  
Cornelius F. Waller ◽  
Jayashree M. Paranjape ◽  
Guiying Li ◽  
Wei Xiao ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cell Line ◽  
Chronic Myelogenous Leukemia ◽  
Leukemia Cell ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Mrna Levels ◽  
Rnase L ◽  
Hematopoietic Stem

We report an RNA targeting strategy, which selectively degrades bcr/abl mRNA in chronic myelogenous leukemia (CML) cells. A 2′,5′-tetraadenylate activator (2-5A) of RNase L was chemically linked to oligonucleotide antisense directed against either the fusion site or against the translation start sequence in bcr/abl mRNA. Selective degradation of the targeted RNA sequences was demonstrated in assays with purified RNase L and decreases of p210bcr/abl kinase activity levels were obtained in the CML cell line, K562. Furthermore, the 2-5A-antisense chimeras suppressed growth of K562, while having substantially reduced effects on the promyelocytic leukemia cell line, HL60. Findings were extended to primary CML cells isolated from bone marrow of patients. The 2-5A-antisense treatments both suppressed proliferation of the leukemia cells and selectively depleted levels of bcr/abl mRNA without affecting levels of β-actin mRNA, determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The specificity of this approach was further shown with control oligonucleotides, such as chimeras containing an inactive dimeric form of 2-5A, antisense lacking 2-5A, or chimeras with altered sequences including several mismatched nucleotides. The control oligonucleotides had either reduced or no effect on CML cell growth and bcr/abl mRNA levels. These findings show that CML cell growth can be selectively suppressed by targeting bcr/abl mRNA with 2-5A-antisense for decay by RNase L and suggest that these compounds should be further explored for their potential as ex vivo purging agents of autologous hematopoietic stem cell transplants from CML patients.

scholarly journals Antiproliferative and proapoptotic effects of a pyrrole containing arylthioindole in human Jurkat leukemia cell line and multidrug-resistant Jurkat/A4 cells

2015 ◽  
Vol 16 (12) ◽  
pp. 1820-1829 ◽  
Author(s):  
Alex A Philchenkov ◽  
Michael P Zavelevich ◽  
Volodymyr P Tryndyak ◽  
Ludmila M Kuiava ◽  
Dmitry Yu Blokhin ◽  
...  
Keyword(s):  
Cell Line ◽  
Leukemia Cell ◽  
Multidrug Resistant ◽  
Leukemia Cell Line

scholarly journals The effect of Kagocel® on gene expression of Toll-like receptors of innate immunity in THP-1 human monocytes with different levels of differentiation

2021 ◽  
Vol 21 (2) ◽  
pp. 116-121
Author(s):  
T. M. Sokolova ◽  
V. V. Poloskov
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Active Ingredient ◽  
Viral Infections ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Acute Monocytic Leukemia ◽  
Toll Like Receptors ◽  
Monocytic Leukemia ◽  
Different Levels

Kagocel® is used in Russia for the treatment of viral infections. In terms of its chemical structure, Kagocel® active ingredient is a copolymer of gossypol polyphenol and carboxymethylcellulose. The study investigated antiviral and cytokine-inducing activity of Kagocel®, as well as its toxic effects. The aim of the study was to investigate the effect of Kagoce ® active ingredient on the induction of expression of the innate immune system receptor genes (Toll-like receptors, TLR) in the THP-1 human acute monocytic leukemia cell line with different levels of differentiation. Materials and methods: the effect of Kagocel active ingredient was investigated at the concentrations of 0.2 and 2 mg/mL in the THP-1 human acute monocytic leukemia cell line with different levels of differentiation: non-differentiated monocytes, and monocytes differentiated into macrophage-like cells. Comparative analysis of the activity of TLR 2, 3, 4, 7, 8, 9 genes was carried out by quantitative RT-PCR. The study determined standard deviations of the levels of gene expression in the experimental cells (2deltaCq ± SD) relative to the expression in the control cells. Results: Kagocel active ingredient at the concentration of 0.2 mg/mL induced activation of TLR2 expression in THP-1 monocytes by 3.5 times, TLR3 by 2 times, TLR4 by 1.6 times, and at the concentration of 2 mg/mL also induced activation of TLR7 and TLR8 by 1.4 times, and TLR9 by 2 times. The levels of TLR2, TLR3, TLR9 induction were significantly higher in THP-1 monocytes partially differentiated into macrophage-like cells, and the highest stimulation level was observed for TLR2 (8 times). Conclusions: the results obtained characterise Kagocel® as a stimulator of TLR genes in the THP-1 cell line. The number of TLR genes induced in THP-1 monocytes was shown to increase with the increase in the product concentration. THP-1 monocyte differentiation into macrophage-like cells enhances susceptibility to Kagocel®. The positive regulation of TLR genes activity may account for antiviral and interferon-inducing properties of Kagocel®, and also suggests the possibility of expanding the use of the product for various immune-associated diseases.

scholarly journals Comparative cellular pharmacology of daunorubicin and idarubicin in human multidrug-resistant leukemia cells

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3267-3273 ◽  
Author(s):  
E Berman ◽  
M McBride
Keyword(s):  
Growth Inhibition ◽  
Cell Line ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Fold Increase ◽  
Multidrug Resistant ◽  
Fresh Medium ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Cellular Pharmacology

We examined the effect of daunorubicin (DNR), the new anthracycline derivative idarubicin (IDR), and verapamil on two leukemia cell lines that displayed the multidrug resistant (MDR) phenotype and used laser flow cytometry to quantitate intracellular anthracycline content. The vinblastine-resistant human lymphoblastic leukemia cell line CEM-VBL demonstrated minimal DNR uptake; simultaneous incubation with verapamil and DNR increased intracellular DNR uptake fourfold. IDR uptake was 10 times more rapid in these cells and simultaneous incubation with IDR and verapamil resulted in only a 1.2-fold increase of intracellular IDR. Similar results were observed in the vincristine-resistant human myeloid leukemia cell line HL-60/RV+. Intracellular retention of DNR and IDR was also measured in each cell line. In CEM-BVL cells, 38% of the original DNR concentration remained after a 2-hour resuspension in fresh medium compared with 71% of the original IDR concentration. In HL- 60/RV+ cells, 36% of the DNR concentration remained compared with 51% of the IDR concentration. After incubation of CEM-VBL and HL-60/RV+ cells with DNR for 1 hour followed by resuspension in fresh medium plus verapamil, intracellular DNA retention increased 5- and 5.2-fold, respectively. However, incubation of these cells for 1 hour with IDR followed by resuspension in fresh medium plus verapamil resulted in only a 1.6- and 2.4-fold increase in intracellular IDR retention. Lastly, clonogenic experiments were performed to correlate intracellular anthracycline content with cytotoxicity. DNR alone had a minimal effect on the clonogenic growth of CEM-VBL cells, whereas the combination of DNR plus verapamil resulted in approximately 80% growth inhibition. However, incubation of these cells with IDR alone resulted in greater than 95% growth inhibition. These results suggest that IDR may be more effective than DNR in leukemia cells that display the MDR phenotype.

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