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

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posted on 2023-05-18, 21:50 authored by Norouzi, S, Norouzi, M, Ayerian, S, Nabiuni, M, Amini, M, Salimi, M

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.

History

Publication title

Physiology and Pharmacology

Volume

18

Pagination

16-26

ISSN

1735-0581

Department/School

School of Health Sciences

Publisher

Iranian Society of Physiology and Pharmacology

Place of publication

Iran

Rights statement

Copyright 2014 Iranian Society of Physiology and Pharmacology. Licensed under Creative Commons Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0) https://creativecommons.org/licenses/by-nc/3.0/

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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