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Two COX-2 inhibitors induce apoptosis in human erythroleukemia K562cells by modulating NF-κB and FHC pathways


Norouzi, S and Norouzi, M and Amini, M and Amanzadeh, A and Nabiuni, M and Irian, S and Salimi, M, Two COX-2 inhibitors induce apoptosis in human erythroleukemia K562cells by modulating NF-κB and FHC pathways, Daru Journal of Pharmaceutical Sciences, 24 pp. 1-9. ISSN 1560-8115 (2016) [Refereed Article]


Copyright Statement

Copyright 2016 Norouzi et al.Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1186/s40199-015-0139-0


BACKGROUND: Leukemia is distinguished by abnormal proliferation of leukocytes. Although there has been some progress in developing novel cancer therapies, no significant improvement was observed in the overall survival rate over the last decade. Selective cyclooxygenase-2 (COX-2) inhibitors are known to inhibit tumor growth by exerting antimetastatic and antiangiogenic effects through inhibition of COX -dependent and independent pathways. The ability of two new triaryl-oxadiazole derivatives, compounds A (3-(4-chlorophenyl) -5-(4-flurophenyl)-4-Phenyl-4,5-dihydro-1,2,4-oxadiazole) and B (3,5-bis(4-chlorophenyl)-4-Phenyl-4,5-dihydro-1,2,4-oxadiazole), to induce apoptosis in human erythroleukemia K562 cells was evaluated and the upstream mechanism was investigated.

METHODS: K562 cells were treated with compounds A and B at their IC50 concentrations and analyzed by DAPI staining and Annexin-V-FLUOS labelling solution. Nuclear factor kappa-B (NF-κB) activation was evaluated by TransAM kit. Cyclooxygenase-2 (COX-2), Caspase-3, Bax, Bcl-2, ferritin heavy chain (FHC), extra cellular signal-regulated kinase (ERK), p-ERK and early growth response protein-1 (Egr1) levels were determined using Western blotting, while c-Myc mRNA level was investigated by RT-PCR.

RESULTS: Changes in nuclear morphology and the increased annexin-V/PI staining revealed the apoptotic cell death in compounds A- and B-treated K562 cells. A significant reduction in NF-κB activity as well as FHC and p-ERK levels were detected in these cells. No change was observed in the levels of Bax, Bcl-2, Caspase-3, COX-2, c-Myc and Egr1, following treatment with the two compounds. Collectively, compounds A and B potentiate apoptosis as shown by DAPI staining, flowcytometry, FHC and p-ERK downregulation and NF-κB inactivation.

CONCLUSION: Two compounds induce apoptosis in a COX-2-independent manner which also appears to be independent from mitochondria, caspase and c-Myc/Egr1 pathways.

Item Details

Item Type:Refereed Article
Keywords:Leukemia, Apoptosis, COX-2, FHC, NF-κB
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Signal transduction
Objective Division:Manufacturing
Objective Group:Human pharmaceutical products
Objective Field:Human pharmaceutical treatments
UTAS Author:Norouzi, S (Mrs Shaghayegh Norouzi)
ID Code:111009
Year Published:2016
Web of Science® Times Cited:10
Deposited By:Health Sciences
Deposited On:2016-08-25
Last Modified:2016-12-19
Downloads:154 View Download Statistics

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