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Article: Suppression of RelA/p65 nuclear translocation independent of IκB-α degradation by cyclooxygenase-2 inhibitor in gastric cancer

TitleSuppression of RelA/p65 nuclear translocation independent of IκB-α degradation by cyclooxygenase-2 inhibitor in gastric cancer
Authors
Issue Date2003
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2003, v. 22 n. 8, p. 1189-1197 How to Cite?
AbstractSelective cyclooxygenase-2 (COX-2) inhibitors are promising anti-inflammatory drugs with potential antitumor activities. The nuclear factor-kappa B (NF-κB) family of proteins is important transcriptional regulators of genes involved in immunity, inflammation, and carcinogenesis. In the present study, we investigated whether and by which molecular mechanism the selective COX-2 inhibitors inhibit NF-κB activation in gastric cancer. The effects of SC236 and its derivative, but devoid of COX-2 enzyme inhibition activity on NF-κB signaling, were evaluated using electromobility shift, transfection, and reporter gene assay. The translocation of RelA/p65 was investigated using Western blotting and immunocytochemistry. We showed that SC236 suppressed NF-κB-mediated gene transcription and binding activity in gastric cancer. This effect occurred through a mechanism independent of cyclooxygenase activity and prostaglandin synthesis. Furthermore, unlike aspirin, SC236 affected neither the phosphorylation, degradation, nor expression of IκB-α, suggesting that the effects of SC236 are independent of IKK activity and IκB-α gene transcription. Instead, SC236 worked directly through suppressing nuclear translocation of RelA/p65. It is possible that SC236 directly targets proteins that facilitate the nuclear translocation of NF-κB. Our study suggests an important molecular mechanism by which COX-2 inhibitors reduce inflammation and suppress carcinogenesis in gastrointestinal tract.
Persistent Identifierhttp://hdl.handle.net/10722/162686
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, BCYen_US
dc.contributor.authorJiang, XHen_US
dc.contributor.authorFan, XMen_US
dc.contributor.authorLin, MCMen_US
dc.contributor.authorJiang, SHen_US
dc.contributor.authorLam, SKen_US
dc.contributor.authorKung, HFen_US
dc.date.accessioned2012-09-05T05:22:21Z-
dc.date.available2012-09-05T05:22:21Z-
dc.date.issued2003en_US
dc.identifier.citationOncogene, 2003, v. 22 n. 8, p. 1189-1197en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/10722/162686-
dc.description.abstractSelective cyclooxygenase-2 (COX-2) inhibitors are promising anti-inflammatory drugs with potential antitumor activities. The nuclear factor-kappa B (NF-κB) family of proteins is important transcriptional regulators of genes involved in immunity, inflammation, and carcinogenesis. In the present study, we investigated whether and by which molecular mechanism the selective COX-2 inhibitors inhibit NF-κB activation in gastric cancer. The effects of SC236 and its derivative, but devoid of COX-2 enzyme inhibition activity on NF-κB signaling, were evaluated using electromobility shift, transfection, and reporter gene assay. The translocation of RelA/p65 was investigated using Western blotting and immunocytochemistry. We showed that SC236 suppressed NF-κB-mediated gene transcription and binding activity in gastric cancer. This effect occurred through a mechanism independent of cyclooxygenase activity and prostaglandin synthesis. Furthermore, unlike aspirin, SC236 affected neither the phosphorylation, degradation, nor expression of IκB-α, suggesting that the effects of SC236 are independent of IKK activity and IκB-α gene transcription. Instead, SC236 worked directly through suppressing nuclear translocation of RelA/p65. It is possible that SC236 directly targets proteins that facilitate the nuclear translocation of NF-κB. Our study suggests an important molecular mechanism by which COX-2 inhibitors reduce inflammation and suppress carcinogenesis in gastrointestinal tract.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_US
dc.relation.ispartofOncogeneen_US
dc.subject.meshActive Transport, Cell Nucleus - Drug Effectsen_US
dc.subject.meshAnti-Inflammatory Agents, Non-Steroidal - Pharmacologyen_US
dc.subject.meshAnticarcinogenic Agents - Pharmacologyen_US
dc.subject.meshAspirin - Pharmacologyen_US
dc.subject.meshColonic Neoplasms - Pathologyen_US
dc.subject.meshCyclooxygenase 2en_US
dc.subject.meshCyclooxygenase 2 Inhibitorsen_US
dc.subject.meshCyclooxygenase Inhibitors - Pharmacologyen_US
dc.subject.meshDna, Neoplasm - Metabolismen_US
dc.subject.meshEnzyme Activation - Drug Effectsen_US
dc.subject.meshHumansen_US
dc.subject.meshI-Kappa B Kinaseen_US
dc.subject.meshI-Kappa B Proteins - Genetics - Metabolismen_US
dc.subject.meshIsoenzymes - Antagonists & Inhibitorsen_US
dc.subject.meshMembrane Proteinsen_US
dc.subject.meshNf-Kappa B - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshNeoplasm Proteins - Antagonists & Inhibitorsen_US
dc.subject.meshPhosphorylation - Drug Effectsen_US
dc.subject.meshProstaglandin-Endoperoxide Synthasesen_US
dc.subject.meshProtein Binding - Drug Effectsen_US
dc.subject.meshProtein Processing, Post-Translational - Drug Effectsen_US
dc.subject.meshProtein-Serine-Threonine Kinases - Metabolismen_US
dc.subject.meshPyrazoles - Pharmacologyen_US
dc.subject.meshStomach Neoplasms - Pathologyen_US
dc.subject.meshSulfonamides - Pharmacologyen_US
dc.subject.meshTetradecanoylphorbol Acetate - Pharmacologyen_US
dc.subject.meshTranscription Factor Relaen_US
dc.subject.meshTranscription, Genetic - Drug Effectsen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTumor Necrosis Factor-Alpha - Pharmacologyen_US
dc.titleSuppression of RelA/p65 nuclear translocation independent of IκB-α degradation by cyclooxygenase-2 inhibitor in gastric canceren_US
dc.typeArticleen_US
dc.identifier.emailWong, BCY:bcywong@hku.hken_US
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_US
dc.identifier.authorityWong, BCY=rp00429en_US
dc.identifier.authorityLin, MCM=rp00746en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.onc.1206234en_US
dc.identifier.pmid12606945-
dc.identifier.scopuseid_2-s2.0-0037468255en_US
dc.identifier.hkuros79126-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037468255&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume22en_US
dc.identifier.issue8en_US
dc.identifier.spage1189en_US
dc.identifier.epage1197en_US
dc.identifier.isiWOS:000181249700007-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridWong, BCY=7402023340en_US
dc.identifier.scopusauthoridJiang, XH=36089034900en_US
dc.identifier.scopusauthoridFan, XM=35187111100en_US
dc.identifier.scopusauthoridLin, MCM=7404816359en_US
dc.identifier.scopusauthoridJiang, SH=7404453122en_US
dc.identifier.scopusauthoridLam, SK=7402279473en_US
dc.identifier.scopusauthoridKung, HF=7402514190en_US

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