Norouzi S, Norouzi M, Ayerian S, Nabiuni M, Amini M, Salimi M. Evaluation of cytotoxicity mechanism of two cyclo-oxygenase-2 inhibitors in leukemia cell line. Physiol Pharmacol 2014; 18 (1) :16-26
URL:
http://ppj.phypha.ir/article-1-955-en.html
Abstract: (9315 Views)
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.