Apoptotic Effects of Two Cox-2 Inhibitors on Breast Adenocarcinoma Cells Through Cox-2 Independent Pathway Publisher Pubmed



Norouzi M¹ ; Norouzi S¹ ; Amini M² ; Amanzadeh A³ ; Irian S¹ ; Salimi M⁴ Show Affiliations
Source: Journal of Cellular Biochemistry Published:2015

Abstract

Recently, much effort has been directed toward the search for compounds that influence apoptosis and to understand their mechanisms of action. Cyclooxygenase (COX)-2 inhibitors may induce apoptosis through the COX-2-independent mechanism via a mitochondrial pathway In view of the reported antiproliferative activities of two COX-2 inhibitor derivatives (1, 2) in breast cancer cells (MCF-7), the present study was undertaken to evaluate the potential of these compounds to induce apoptosis and unravel the associated mechanisms. The apoptotic activities of the two compounds were assessed using flow cytometry, fluorescence microscope, and Western blot analysis. Compounds 1 and 2-treated MCF-7 cells revealed the apoptotic cell death, as confirmed by the changes in nuclear morphology and the increased annexin-V/PI staining Elevation of BaxtoBcl-2 ratio and activationof caspase-3 were found to be associated with the initiation ofapoptosis induced bycompound 1 Further investigation showed that compounds 1 and 2 inhibited NF-κB, FHC, and ERK activation, while no dramatic change was revealed in c-Myc and EGR-1 levels. Our data suggest that induction of apoptosis by compounds 1 and 2 is not associated with COX-2 expression and occurs through the NF-κB pathway, which sequentially inhibits P-ERK and FHC expression. © 2014 Wiley Periodicals, Inc.