scholarly journals Inhibition of Glucose-6-Phosphate Dehydrogenase Could Enhance 1,4-Benzoquinone-Induced Oxidative Damage in K562 Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Juan Zhang ◽  
Meng Cao ◽  
Wenwen Yang ◽  
Fengmei Sun ◽  
Cheng Xu ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Cell Line ◽  
K562 Cell ◽  
K562 Cells ◽  
Control Group ◽  
K562 Cell Line ◽  
G6pd Gene ◽  
Oxidative Metabolites ◽  
Chemical Contaminant ◽  
Glucose 6 Phosphate Dehydrogenase

Benzene is a chemical contaminant widespread in industrial and living environments. The oxidative metabolites of benzene induce toxicity involving oxidative damage. Protecting cells and cell membranes from oxidative damage, glucose-6-phosphate dehydrogenase (G6PD) maintains the reduced state of glutathione (GSH). This study aims to investigate whether the downregulation of G6PD in K562 cell line can influence the oxidative toxicity induced by 1,4-benzoquinone (BQ). G6PD was inhibited in K562 cell line transfected with the specific siRNA of G6PD gene. An empty vector was transfected in the control group. Results revealed that G6PD was significantly upregulated in the control cells and in the cells with inhibited G6PD after they were exposed to BQ. The NADPH/NADP and GSH/GSSG ratio were significantly lower in the cells with inhibited G6PD than in the control cells at the same BQ concentration. The relative reactive oxygen species (ROS) level and DNA oxidative damage were significantly increased in the cell line with inhibited G6PD. The apoptotic rate and G2 phase arrest were also significantly higher in the cells with inhibited G6PD and exposed to BQ than in the control cells. Our results suggested that G6PD inhibition could reduce GSH activity and alleviate oxidative damage. G6PD deficiency is also a possible susceptible risk factor of benzene exposure.

scholarly journals Absorption Characteristics of Combination Medication of Realgar and Indigo Naturalis: In Vitro Transport across MDCK-MDR1 Cells and In Vivo Pharmacokinetics in Mice after Oral Administration

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Miao Zhang ◽  
Lin Guo ◽  
Long-Fei Lin ◽  
Chang-Hai Qu ◽  
Xing-Bin Yin ◽  
...  
Keyword(s):  
Cell Line ◽  
K562 Cell ◽  
Computational Study ◽  
Arsenic Concentration ◽  
K562 Cells ◽  
Cell Permeability ◽  
K562 Cell Line ◽  
Apparent Permeability ◽  
Indigo Naturalis

Realgar and indigo naturalis are clinically combined to treat varieties of leukemia. Exploring the drug-drug interactions might be beneficial to find active substances and develop new targeted drugs. This study aimed at exploring the change of arsenic concentration in mice and across MDCK-MDR1 cells and the cytotoxicity on K562 cells when realgar and indigo naturalis were combined. In the presence or absence of indigo naturalis, pharmacokinetics and cell-based permeability assays were used to evaluate the change of arsenic concentration, and K562 cell line was applied to evaluate the change of cytotoxicity. The drug concentration-time profiles exhibited that the combination medication group generated higher AUC, thalf, and longer MRT for arsenic, compared with the single administration of realgar. The apparent permeability coefficients (Papp) of bidirectional transport in MDCK-MDR1 cell permeability experiments showed that arsenic permeability obviously went up when indigo naturalis was incubated together. The combination medication significantly decreased the cell viability of K562 cells when both the concentration of realgar and the concentration of indigo naturalis were nontoxic. The pharmacokinetic research, the MDCK-MDR1 based permeability study, and the K562 cytotoxicity study were united together to verify the combination medication of realgar and indigo naturalis enhanced the absorption and the permeability across cells for arsenic and effectively inhibited the proliferation of K562 cell line. The molecular binding of As4S4 and indirubin was analyzed by computational study. It is predicted that the formation of the complex [As4S4…Indirubin] involves noncovalent interaction that changes the concentration of arsenic.

Effect of Hypoxia on the Expression of BRIT1 in K562 Cell Line: Implication for Resistance to Imatinib.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4530-4530
Author(s):  
Cesarina Giallongo ◽  
Daniele Tibullo ◽  
Piera La Cava ◽  
Annalisa Chiarenza ◽  
Salvatore Berretta ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Line ◽  
K562 Cell ◽  
K562 Cells ◽  
Hypoxic Condition ◽  
Culture Conditions ◽  
K562 Cell Line ◽  
Total Rna ◽  
Taqman Gene Expression Assay ◽  
Cell Mortality

Abstract BRIT1 (Microcephalin, MCPH1) is a chromatin binding protein that forms ionizing irradiation-induced nuclear foci (IRIF); it is a crucial DNA damage regulator in the ATM/ATR pathways. Here we have analyzed BRIT1 expression on K562 cell line after treatment with imatinib 0,1-1 μM, UV irradiation (12 μJ/cm2) and after exposure to an hypoxic condition (3% O2). K562 in standard culture conditions (21% O2) were used to establish BRIT1 basal expression. Total RNA from K562 cultures was prepared at 24 and 48 hs. 1 μg total RNA was reverse transcribed from each sample. TaqMan Gene expression assay (Applied Biosystems) in Real-Time PCR was employed to examine the expression of BRIT1. Cellular count was assayed by trypan blue. Treatment with IM (0,1 and 1 μM) and UV induced a 2–3 fold increased expression of BRIT1 at 24 h and a minor increase at 48 h. Cell mortality at 24 h was 30% for IM and 20% for UV while at 48 h cells started to grow again, possibly as a consequence of the DNA damage repair by BRIT1. Exposure of K562 cells to hypoxia increased BRIT1 expression about 5- and 6-folds at 24 and 48 h respectively. Cell mortality at 24 h was 30% while after 48 h it was 20%. We therefore concluded that BRIT1 expression increases in hypoxia more than after IM and UV exposure. Since we have found that K562 in hypoxic conditions are relatively resistant to imatinib, (K562 cell mortality after 24 h exposure to IM 1μM was 30% ± 0,3 in normoxia vs 9% ± 0,8 in hypoxia, P<0,005) we have hypothesized that BRIT1 could be involved in resistance to IM. Therefore, we exposed K562 to UV and, after 48 h we incubated the cells with imatinib 1 μM. Pre-exposure of K562 cells to UV reduced imatinib-induced mortality (9,7% ± 1,6 vs 21,3% ± 1,5 of control, p< 0,005) thus indicating that upregulation of BRIT1 (as we have observed especially in hypoxia) could contribute to resistance to imatinib in K562 cell line. Understanding of BRIT1 function may well contribute to novel therapeutic approaches for cancer.

The Effect of Imatinib Mesylate on the Signal Transduction Cascade Leading to down Regulation of Telomerase Activity in K562 Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4787-4787
Author(s):  
Rahav Mor ◽  
Orit Uziel ◽  
Ofer Shpilberg ◽  
Judith Lahav ◽  
Pia Raanani ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Tyrosine Kinase ◽  
Cell Line ◽  
Imatinib Mesylate ◽  
K562 Cell ◽  
K562 Cells ◽  
Telomerase Activity ◽  
K562 Cell Line ◽  
Signal Transduction Cascade ◽  
Cellular Components

Abstract Imatinib mesylate (IM) is a tyrosine kinase inhibitor selective for Bcr-Abl, c-Kit, and platelet-derived growth factor receptor kinases. IM inhibits kinase activity through competition for ATP binding. IM is indicated for the treatment of newly diagnosed patients with Philadelphia chromosome positive (BCR-ABL positive) chronic myeloid leukemia (CML) in chronic phase. Recent publications demonstrate that this drug may also target other cellular components. In light of the important role of telomerase in malignant transformation, we evaluated the effect of IM on the signal transduction cascade leading to modulation of telomerase activity in the BCR-ABL positive K562 cell-line. In addition, we studied the effect of IM on telomerase in an IM resistant K562 cell-line (K562res). The K562res cell-line is resistant to the effect of IM on the BCR-ABL protein. However, the effect of IM on telomerase in these cells is unknown. Therefore, using these cells will enable us to study the connection between the signal transduction cascade of BCR-ABL and that of telomerase. IM caused an 80% inhibition of telomerase activity in both K562 and K562res cell-lines. Inhibition of telomerase activity was associated with 50% inhibition of proliferation. Inhibition of telomerase activity was not caused by changes in the transcription level of hTERT (the catalytic subunit of the enzyme). On the other hand, it seemed mainly to be caused by post-translational modifications only in K562 cells namely, a 2-fold dephosphorylation of AKT, known to phosphorylate telomerase. In addition, IM was found to upregulate the expression of PTEN (known to negatively regulate AKT) again only in K562 cells. IM did not affect the levels of phosphorylaetd AKT or PTEN in K562res cells. However, IM caused an approximate 2-fold upregulation of p53 (a transcription factor of PTEN) levels both in K562 and K562res cells. Our results demonstrate the ability of IM to inhibit telomerase activity in BCR-ABL expressing cell lines. Telomerase activity inhibition was demonstrated in K562 cells as well as in K562 cells resistant to high concentrations of IM. Therefore, the inhibitory effect of IM on telomerase activity isn’t necessarily mediated through the known tyrosine kinase targets of IM. The effect of IM on the signal transduction cascade leading to the down-regulation of telomerase activity seems to be different in K562 cells and K562res cells. While the signal transduction cascade in K562 cells appears to go through AKT and PTEN, the response to IM in K562res cells seems to be mediated by other yet unknown pathways. Future work is needed in order to clarify possible mechanism(s) by which IM down-regulates telomerase activity in these cells. This study supports previous studies demonstrating telomerase activity as an additional cellular target of IM. In addition, this study shows that cells known to be resistant to IM with regards to its effect on BCR-ABL could still be sensitive to IM treatment regarding other cellular components.

Pharmacologic Doses of Amiloride Preferentially Induce Apoptosis and Growth Inhibition of Flt3-ITD Mutation Positive Acute Myeloid Leukemia Cell Lines

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5004-5004
Author(s):  
Yuliya Linhares ◽  
Jade Dardine ◽  
Siavash Kurdistani
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Cell Lines ◽  
K562 Cell ◽  
Myeloid Leukemia ◽  
K562 Cells ◽  
K562 Cell Line ◽  
Cycle Arrest

Abstract Abstract 5004 Introduction: Amiloride is an FDA approved potassium-sparing diuretic which targets Na+/H+ exchanger isoform 1 (NHE1). NHE1 is responsible for the regulation of the intracellular pH, as well as cell-cycle and apoptosis. In supra-pharmacologic concentrations, amiloride non-specifically inhibits protein kinases. Recent study demonstrated that proapoptotic effect of amiloride in CML cell lines is linked to the modulation of the alternative splicing of Bcl-x, HIPK3, and BCR/ABL genes and is independent of pHi. Here, we demonstrate that pharmacologic doses of amiloride preferentially induce growth inhibition, cell cycle arrest and apoptosis in Flt3-ITD positive acute myeloid leukemia cell lines as compared to Bcr-Abl positive leukemia cell line. Our data suggests that amiloride may have an effect on Flt3 signaling and that its treatment potential for Flt3-ITD positive acute myeloid leukemia needs to be explored. Methods: MV4-11, MOLM13 and K562 cells lines in log-phase growth were used for the experiments. Analysis of the baseline Flt3 expression and phosphorylation status was assessed via Flt3 immunoprecipitation and Western blotting for Flt3 and phosphotyrosine. Cells were incubated with various amiloride concentrations; equal volume dilutions of DMSO were used for control. Cell counting and trypan blue exclusion viability was performed on TC10 Bio-Rad automated cell counter. The cell cycle analysis was performed applying propidium iodide staining. To assess for apoptosis and cell death, we used annexin V/PI staining kit and flow cytometry. Results: MOLM13 and MV4-11 cell lines carry activating Flt3-ITD mutation. We confirmed the expression and constituative activation of Flt3 in MOLM13 and MV4-11 cells with Western blotting. Flt3 protein was not detectable in K562 cell line. Amiloride at 0.025 mM and 0.05 mM completely inhibited the growth of MV4-11 cells after 24 hrs of treatment with no significant increase in total or live cell numbers at 72 hrs, but only mildly affected K562 cell proliferation. While the above amiloride concentrations caused cell death in MV4-11 and MOLM13 cell lines, there was no increased cell death in K562 cells. Incubation of MOLM13 and MV4-11 cell lines with 0.05 mM amiloride for 20 hrs induced cell cycle arrest. In MV4-11 cell line, the proportion of S phase cells after amiloride treatment was 15.4% (SD=5.4%) as compared to 31.3% (SD=1.4%) in control. MOLM13 cell line demonstrated 15.3% (SD=4.7%) of cells in S after amiloride treatment as compared to 35.3% (SD=2.4%) cells in S phase in control treatment. In K562 cell line, there was less effect with 52% (SD=4.2%) of cells in S phase in control as compared to 37% (SD=8.9%) in amiloride treatment. MV4-11 and MOLM 13 cell lines were more sensitive than K562 cells to amiloride induced apoptosis with 28.8% (control 12.7%) of MV4-11 cells, 11.4% (control 7.4%) of MOLM13 cells, and 11.4% (control 8.6%) of K562 cells being apoptotic after 20 hr treatment with 0.05mM amiloride. At 72 hrs of amiloride treatment 34% (control 1.5%) of MV4-11 cells, 17% (control 5%) of MOLM13 cells and 11% of K562 cells (control 8.9%) were apoptotic. Amiloride had similar effect on the number of dead cells with no increase in total cell death in K562 cell line. Upon treatment with increasing amiloride concentrations, there was dose-dependent increase in cell death and apoptosis in all three cell lines with K562 line showing relative resistance to amiloride. Discussion: Our results demonstrate that amiloride induces cell cycle arrest and inhibits proliferation of Flt3-ITD positive cell lines MV4-11 and MOLM13 as well as K562 cell line at a pharmacologic concentration of 0.05 mM. Both, cell cycle arrest and antiproliferative effect are more pronounced in Flt3-ITD positive cells lines while it is mild in Bcr-Abl positive K562 cell line. Pharmacologic doses of amiloride induce cell death and apoptosis in Flt3-ITD positive cell lines but not in K562 cell line. Both, Bcr-Abl and Flt3 signaling stimulates proliferation and inhibits apoptosis in myeloid leukemia cells. Our study suggests that amiloride may induce cell cycle arrest and apoptosis via modulating Flt3 signaling cascade. We are currently investigating the effects of amiloride on Flt3 phosphorylation. In conclusion, our data suggests that amiloride presents a potential treatment option for Flt3-ITD positive acute myeloid leukemia. Disclosures: No relevant conflicts of interest to declare.

The Adaptor Protein SLP-76 Is Not a Direct Substrate for BCR-ABL in the Chronic Myeloid Leukemia Cell Line K562.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4699-4699
Author(s):  
Witzard Joseph ◽  
Nancy Luckashenak ◽  
Kimberly Ramsey ◽  
James Clements ◽  
Swami Padmanabhan
Keyword(s):  
T Cell ◽  
Tyrosine Kinase ◽  
Cell Line ◽  
Tyrosine Phosphorylation ◽  
K562 Cell ◽  
Adaptor Protein ◽  
K562 Cells ◽  
Leukemia Cell Line ◽  
K562 Cell Line ◽  
Associated Proteins

Abstract SLP-76(SH2 domain-containing leukocyte protein of 76 kD) is a hematopoietic adapter protein that is expressed in myeloid and T cells. SLP-76 is a substrate for tyrosine kinase in the src and syk family activation pathway required for T-cell receptor-mediated signaling. Cross-linking of the human FcgammaRIIa1 (CD32) in myeloid cells which contains an immune receptor tyrosine-based activation motif (ITAM) causes phosphorylation of SLP-76. Mice deficient in SLP76 develop fetal hemorrhage along with failure of T cell development and perinatal mortality. We have found that K562 cells express SLP-76. We hypothesized that SLP-76 or associated proteins may be substrates of Bcr-Abl in the K562 cell line and thus promote survival signals. Materials and Methods: The K-562 cell line was obtained from the American collection of Cell Cultures. SLP deficient (−/−) KO mice were obtained from Dr. James Clements (Roswell Park Cancer Institute). Antibodies used include Sheep polyclonal IgG Anti-Human SLP 76, Peroxidase-conjugated Affinipure Donkey Anti-Sheep IgG at 0.8mg/ml, Mouse monoclonal IgG Anti-Phosphotyrosine, and Polyclonal goat Anti-mouse. Immunoprecipitation and Immunoblot: Cells were either untreated or stimulated with purvanidate (phosphatase inhibitors). Purvanidate treated cells were used as a positive control. Spleenocytes isolated from a SLP-76 deficient mouse (KO) were used as negative control. Lysates were then subject to standard immunoprecipitation for SLP-76 followed by immunoblotting with a SLP-76 specific antibody. The denatured samples were then resolved by SDS-PAGE. Results: SLP-76 is expressed in untreated and treated K562 with purvanidate and not detectable from lysates derived from SLP-76 KO spleenocytes. To assess the phosphorylation status of SLP-76 and any co-associated proteins in K562 cells, the SLP-76 blot was stripped and then immunoblotted for total phosphotyrosine content. SLP-76 does not appear to be constitutively phosphorylated in the K562 cells. However, significant tyrosine phosphorylation of SLP-76 was readily detectable in the purvanidate treated K562 cells. Conclusion: The current studies reveal that although SLP-76 is indeed found in the K562 cell line expressing the Bcr-Abl oncogene. Somewhat surprisingly, despite the constitutive activation of the Bcr-Abl tyrosine kinase in K562 cells, we detected no obvious phosphoproteins co-precipitating with SLP-76 in the absence of purvanidate stimulation. Together, the lack of SLP-76 tyrosine phosphorylation and the lack of co-associated proteins in K562 cells suggest that SLP-76 is not a major player in the signal transduction pathways emanating from Bcr-Abl. However, a more stringent confirmation of this conclusion would require inhibiting SLP-76 expression in K562 cells and than assessing the growth and survival characteristics. Figure Figure

The Transcription Factor SCL/TAL-1 Plays a Positive Role in the Erythropoietic Differentiation Via MEK/ERK Pathway in EPO-Induced K562 Cell Line

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4799-4799
Author(s):  
Yuping Gong ◽  
Ruiqing Zhou ◽  
Ting Niu
Keyword(s):  
Transcription Factor ◽  
Cell Line ◽  
K562 Cell ◽  
K562 Cells ◽  
Erythroid Differentiation ◽  
Mrna Levels ◽  
Erk Pathway ◽  
Rt Pcr ◽  
K562 Cell Line ◽  
Positive Role

Abstract Abstract 4799 Objective In the present study, EPO-induced K562 cell line was used to be the cell model of erythroid differentiation, the role and mechanism of transcript factor SCL/TAL-1 in the erythropoiesis was investigated. Methods Three plasmids, which included pTRIPdU3-RNAiTALh -EF1a-GFP (SCL/TAL1 shRNA to reduce the expression of SCL/TAL-1), pTRIP-EF1a-TAL1 (SCL/TAL-1 cDNA to enhance the expression of SCL/TAL-1) and control plasmid pTRIP-dU3-RNAiluc-EF1-GFP expressing EGFP gene, were transfected into K562 cell line via lentiviral vector system, and K562 SCL/TAL-1low, K562 SCL/TAL-1high and K562 LUC (control) were established and the effect of reducing or enhancing the expression of SCL/TAL-1 on the erythropoiesis of these three cell lines was investigated. After incubated with EPO-RPMI1640 medium in which EPO induced K562 cell line into erythropoiesis for 5 day, the mRNA levels of SCL/TAL-1 and erythroid related RhD, GPA, CD47 were detected by RT-PCR assay and erythroid antigen CD71, CD235a were examined by flow cytometry in the three cell lines. Effect of SCL/TAL-1 on key phosphorylated proteins, including p-PTEN, p-Akt, p-mTOR, p-P70 and p-4EBP-1 from PI3K/Akt/mTOR pathway and p-c-Raf, p-MEK and p-ERK1/2 from Raf/MEK/ERK pathway, in the downstream of EGFR signaling pathway were checked by Western Blot assay. Effect of MEK-ERK 1/2 inhibitor U0126 on the expression of SCL/TAL1 also examined. Results 1. After 48h of transfect, more than 95% of K562 cells were GFP positive under the fluorescence microscope, indicating that infection rate of the plasmids in the K562 cells was more than 95%. 2. The results of RT-PCR showed SCL/TAL-1 mRNA expression in the K562 SCL/TAL-1low was significantly lower than that in the K562 LUC control (P <0.05). The mRNA levels of CD47 and RhD was also significantly lower and however, GPA just decreased slightly in comparison with the control. The mRNA levels of above erythroid antigens increased a little in K562-SCL/TAL-1high. 3. The FCM results showed the expression of CD71, CD235a obviously reduced in the K562 SCL/TAL-1low and positive rates were 10.4% and 76.5%, while the positive rates in the LUC control were 94.3% and 83.6%. The expression of CD71 and CD235a in K562-SCL/TAL-1high was similar to the control. 4. The level of p-MEK and p-ERK1/2 increased with transfect of SCL/TAL-1 cDNA and decreased after SCL/TAL-1 RNA interference. However, there were no obvious changes to be observed in PI3K-Akt-mTOR pathway, another important signal pathway. 5. There was no obvious alteration in SCL/TAL-1 level after treatment of MEK-ERK1/2 inhibitor, although MEK-ERK1/2 level reduced. Conclusion Our findings suggest that transcription factor SCL/TAL-1 plays a positive role in erythroid differentiation in EPO-induced K562 cell line. SCL/TAL-1 is located in the upstream of MEK-ERK1/2 and may regulate erythroid differentiation by affecting the phosphorylation levels of MEK-ERK1/2 pathway. Grant support: National Natural Science Foundation of China (No.30770912), Foundation of the Science & Technology Department of Sichuan Province (No.2008SZ0017). Disclosures: No relevant conflicts of interest to declare.

A New Series of Antileukemic Agents: Design, Synthesis, In Vitro and In Silico Evaluation of Thiazole-Based ABL1 Kinase Inhibitors

2020 ◽  
Vol 20 ◽  
Author(s):  
Ebru Zeytün ◽  
Mehlika D. Altıntop ◽  
Belgin Sever ◽  
Ahmet Özdemir ◽  
Doha E. Ellakwa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Line ◽  
Antiproliferative Activity ◽  
In Silico ◽  
K562 Cell ◽  
Kinase Inhibitors ◽  
K562 Cell Line ◽  
Cytotoxic Effects ◽  
Atp Binding Site

Background: After the milestone approval of imatinib, more than 25 antitumor agents targeting kinases have been approved, and several promising candidates are in various stages of clinical evaluation. Objectives : Due to the importance of thiazole scaffold in targeted anticancer drug discovery, the goal of this work is the design of new thiazolyl hydrazones as potent ABL1 kinase inhibitors for the management of chronic myeloid leukemia (CML). Methods: New thiazolyl hydrazones (2a-p) were synthesized and investigated for their cytotoxic effects on K562 CML cell line. Compounds 2h, 2j and 2l showed potent anticancer activity against K562 cell line. The cytotoxic effects of these compounds on other leukemia (HL-60, MT-2 and Jurkat) and HeLa human cervical carcinoma cell lines were also investigated. Furthermore, their cytotoxic effects on mitogen-activated peripheral blood mononuclear cells (MA-PBMCs) were evaluated to determine their selectivity. Due to its selective and potent anticancer activity, compound 2j was benchmarked for its apoptosis-inducing potential on K562 cell line and inhibitory effects on eight different tyrosine kinases (TKs) including ABL1 kinase. In order to investigate the binding mode of compound 2j into the ATP binding site of ABL1 kinase (PDB: 1IEP), molecular docking study was conducted using MOE 2018.01 program. The QikProp module of Schrödinger’s Molecular modelling package was used to predict the pharmacokinetic properties of compounds 2a-p. Results: 4-(4-(Methylsulfonyl)phenyl)-2-[2-((1,3-benzodioxol-4-yl)methylene)hydrazinyl]thiazole (2j) showed antiproliferative activity against K562 cell line with an IC50 value of 8.87±1.93 µM similar to imatinib (IC50= 6.84±1.11 µM). Compound 2j was found to be more effective than imatinib on HL-60, Jurkat and MT-2 cells. Compound 2j also showed cytotoxic activity against HeLa cell line similar to imatinib. The higher selectivity index value of compound 2j than imatinib indicated that its antiproliferative activity was selective. Compound 2j also induced apoptosis in K562 cell line more than imatinib. Among eight TKs, compound 2j showed the strongest inhibitory activity against ABL1 kinase enzyme (IC50= 5.37±1.17 µM). According to molecular docking studies, compound 2j exhibited high affinity to the ATP binding site of ABL1 kinase forming significant intermolecular interactions. On the basis of in silico studies, this compound did not violate Lipinski's rule of five and Jorgensen's rule of three. Conclusion: Compound 2j stands out as a potential orally bioavailable ABL1 kinase inhibitor for the treatment of CML.

Optimization of differentiation condition for K562 cell line and rat erythroleukemia cell line

2018 ◽  
Vol 295 ◽  
pp. S251
Author(s):  
M. Otani ◽  
K. Iwashita ◽  
T. Utsumi ◽  
S. Kawamura
Keyword(s):  
Cell Line ◽  
K562 Cell ◽  
K562 Cell Line ◽  
Erythroleukemia Cell

Tyrosine Kinase Inhibitor STI571 (Imatinib) Cooperates with Wild-Type p53 on K562 Cell Line to Enhance Its Proapoptotic Effects

2005 ◽  
Vol 114 (3) ◽  
pp. 150-154 ◽  
Author(s):  
Gianluca Brusa ◽  
Manuela Mancini ◽  
Fabio Campanini ◽  
Alberto Calabrò ◽  
Elisa Zuffa ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Line ◽  
K562 Cell ◽  
Kinase Inhibitor ◽  
Wild Type ◽  
K562 Cell Line ◽  
Wild Type P53
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