Salimi, M and Norouzi, S and Norouzi, M and Amini, M and Amanzadeh, A, COX-2 independent induction of apoptosis by two synthetic COX-2 inhibitors in breast cancer cell line, European Journal of Cancer, pp. S40. ISSN 0959-8049 (2014) [Conference Extract]
Background: Breast cancer is considered to be the most familiar malignant tumor in females in western countries; and is becoming more and more widespread in Asia. Apoptosis is an intricate molecular program with favorable application in many tumor treatments. 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 compounds 1 (3-(4-chlorophenyl)-5-(4-fluorophenyl)-4-phenyl-4,5-dihydro-1,2,4- oxadiazole) and 2 (3,5-bis(4-chlorophenyl)-4-phenyl-4,5-dihydro-1,2,4-oxadiazole) as two COX-2 inhibitor derivatives 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.
Material and Methods: The apoptotic activities of compounds 1 and 2 were assessed using flowcytometry. Protein expression was determined by western blot analysis and immunoassay kit.
Results: Compounds 1 and 2 induced MCF-7 cells to undergo apoptosis, which was demonstrated by annexin-V and propidium iodide staining. Further investigation showed that compounds 1 and 2 inhibited nuclear factor kappalight-chain-enhancer of activated B cells (NF-úB), ferritin heavy chain (FHC) and extra cellular signal-regulated kinase (ERK) activation, whereas it could not change COX-2, c-Myc and early growth response protein 1 (EGR-1) expression dramatically.
Conclusion: Altogether, these results revealed that compounds 1 and 2 may be potential and promising chemotherapeutic agents to treat breast cancer through COX-2-independent and NF-úB-dependent pathways, which sequentially inhibit P-ERK and FHC expressions.
|Item Type:||Conference Extract|
|Keywords:||COX-2 inhibitor, Breast cancer, Apoptosis|
|Research Division:||Biological Sciences|
|Research Group:||Biochemistry and cell biology|
|Research Field:||Signal transduction|
|Objective Group:||Human pharmaceutical products|
|Objective Field:||Human pharmaceutical treatments|
|UTAS Author:||Norouzi, S (Mrs Shaghayegh Norouzi)|
|Deposited By:||Health Sciences|
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