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• W1522455546 endingPage "2022" @default.
• W1522455546 startingPage "2011" @default.
• W1522455546 abstract "Abstract The cyclooxygenase 2 (COX-2) inhibitor celecoxib (also called celebrex), approved for the treatment of colon carcinogenesis, rheumatoid arthritis, and other inflammatory diseases, has been shown to induce apoptosis and inhibit angiogenesis. Because NF-κB plays a major role in regulation of apoptosis, angiogenesis, carcinogenesis, and inflammation, we postulated that celecoxib modulates NF-κB. In the present study, we investigated the effect of this drug on the activation of NF-κB by a wide variety of agents. We found that celecoxib suppressed NF-κB activation induced by various carcinogens, including TNF, phorbol ester, okadaic acid, LPS, and IL-1β. Celecoxib inhibited TNF-induced IκBα kinase activation, leading to suppression of IκBα phosphorylation and degradation. Celecoxib suppressed both inducible and constitutive NF-κB without cell type specificity. Celecoxib also suppressed p65 phosphorylation and nuclear translocation. Akt activation, which is required for TNF-induced NF-κB activation, was also suppressed by this drug. Celecoxib also inhibited the TNF-induced interaction of Akt with IκBα kinase (IKK). Celecoxib abrogated the NF-κB-dependent reporter gene expression activated by TNF, TNF receptor, TNF receptor-associated death domain, TNF receptor-associated factor 2, NF-κB-inducing kinase, and IKK, but not that activated by p65. The COX-2 promoter, which is regulated by NF-κB, was also inhibited by celecoxib, and this inhibition correlated with suppression of TNF-induced COX-2 expression. Besides NF-κB, celecoxib also suppressed TNF-induced JNK, p38 MAPK, and ERK activation. Thus, overall, our results indicate that celecoxib inhibits NF-κB activation through inhibition of IKK and Akt activation, leading to down-regulation of synthesis of COX-2 and other genes needed for inflammation, proliferation, and carcinogenesis." @default.
• W1522455546 created "2016-06-24" @default.
• W1522455546 creator A5025131780 @default.
• W1522455546 creator A5048675624 @default.
• W1522455546 creator A5085218671 @default.
• W1522455546 date "2004-08-01" @default.
• W1522455546 modified "2023-10-03" @default.
• W1522455546 title "Cyclooxygenase (COX)-2 Inhibitor Celecoxib Abrogates TNF-Induced NF-κB Activation through Inhibition of Activation of IκBα Kinase and Akt in Human Non-Small Cell Lung Carcinoma: Correlation with Suppression of COX-2 Synthesis" @default.
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• W1522455546 doi "https://doi.org/10.4049/jimmunol.173.3.2011" @default.
• W1522455546 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15265936" @default.
• W1522455546 hasPublicationYear "2004" @default.
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