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Evaluation of cytotoxicity mechanism of two cyclo-oxygenase-2 inhibitors in leukemia cell line


Norouzi, S and Norouzi, M and Ayerian, S and Nabiuni, M and Amini, M and Salimi, M, Evaluation of cytotoxicity mechanism of two cyclo-oxygenase-2 inhibitors in leukemia cell line, Physiology and Pharmacology, 18, (1) pp. 16-26. ISSN 1735-0581 (2014) [Refereed Article]


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Copyright 2014 Iranian Society of Physiology and Pharmacology. Licensed under Creative Commons Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0)

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Introduction: Leukemia is considered one of the main causes of death, and current chemotherapeutic agents are unable to provide optimal responses due to chemo-resistance. Therefore, there is a constant need for new drugs. Cyclooxygenase-2 (COX-2) inhibitors can be helpful by reducing the necessary dose of routine chemotherapeutic drugs. Herein, we evaluated the cytotoxicity activity as well as the morphological changes induced by 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) as COX-2 inhibitors. In addition, the upstream mechanism was investigated by measuring expression of nuclear factor kappa light-chain-enhancer of activated B cells (NF-κB) and ferritin heavy chain (FHC).

Methods: K562 leukemia cell line was cultured, treated with the above-mentioned two compounds, and their IC50 values obtained. Compounds A and B-treated cells were analyzed for morphologic changes by fluorescence microscope after 16 h incubation at their IC50 concentrations. The protein fraction of whole cell lysate was prepared to evaluate NF- κB by NF-κB assay kit. FHC expression was also determined using western blotting.

Results: Treatment of cells with the compounds A and B resulted in considerable apoptotic morphological changes according to DAPI staining. NF-κB assay demonstrated its significant decrease due to compound B. Our experiment also revealed a significant reduction in FHC expression after treatment with compound B.

Conclusion: Compound B can induce cytotoxicity and morphological changes in leukemic cell line probably through NF-κB/FHC pathway.

Item Details

Item Type:Refereed Article
Keywords:COX-2, Leukemia, FHC, NF-κB
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Signal transduction
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Norouzi, S (Mrs Shaghayegh Norouzi)
ID Code:111022
Year Published:2014
Deposited By:Health Sciences
Deposited On:2016-08-26
Last Modified:2016-10-11
Downloads:86 View Download Statistics

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