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Apoptotic Effects of celecoxib derivatives on MCF-7 and K562 cell lines
thesis
posted on 2023-05-26, 13:33 authored by Norouzi, SApoptosis is an intricate molecular program with favorable application in many tumor treatments. Much effort has been directed towards the search for compounds that influence apoptosis and understanding their mechanisms of action. Cyclooxygenase (COX)-2 inhibitors may induce apoptosis through the COX-2-independent mechanism. In view of the reported anti proliferative activities of compounds A (3-(4-chlorophenyl) -5-(4-flurophenyl)- 4-phenyl-4, 5-dihydro-1,2,4-oxadiazole) and B (4-Phenyl-3,5-bis(4-chlorophenyl)-4,5- dihydro-1,2,4-oxadiazole) as two COX-2 inhibitor derivatives in leukemia (K562) and 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. Compounds A and B-treated K562 and MCF-7 cells revealed the apoptotic cell death, as confirmed by the increased annexin-V/PI staining. Further investigation showed that compounds A and B inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), ferritin heavy chain (FHC) and extra cellular signal-regulated kinase (ERK) activation, whereas it could not change c-Myc and early growth response protein 1(EGR-1) expression dramatically. Altogether, our data suggest that induction of apoptosis by compounds A and B is not associated with COX-2 expression and occurs through the NF-ĸB pathway, which sequentially inhibits P-ERK and FHC expression.
History
Department/School
School of Health SciencesPublisher
Kharazmi University of TehranRepository Status
- Restricted