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Article: Dual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smoke

TitleDual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smoke
Authors
Issue Date2005
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2005, v. 26 n. 4, p. 827-834 How to Cite?
AbstractPrevious studies indicate that the arachidonic acid-metabolizing enzymes COX-2 and 5-LOX are overexpressed during the process of colonic adenoma formation promoted by cigarette smoke. The aims of the present study were to investigate whether there exists a relationship between COX-2 and 5-LOX, and whether dual inhibition of COX-2 and 5-LOX has an anticarcinogenic effect in the colonic tumorigenesis promoted by cigarette smoke. Results showed that pretreating colon cancer cells with cigarette smoke extract (CSE) promoted colon cancer growth in the nude mouse xenograft model. Inhibition of COX-2 or 5-LOX reduced the tumor size. In the group treated with COX-2-inhibitor, the PGE 2 level decreased while the LTB4 level increased. In contrast, in the 5-LOX-inhibitor treated group, the LTB4 level was reduced and the PGE2 level was unchanged. However, combined treatment with both COX-2 and 5-LOX inhibitors further inhibited the tumor growth promoted by CSE over treatment with either COX-2-inhibitor or 5-LOX-inhibitor alone. This was accompanied by the downregulation of PGE2 and LTB4. In an in vitro study, we found that the action of CSE on colon cancer cells was mediated by 5-LOX DNA demethylation. In summary, these results indicate that inhibition of COX-2 may lead to a shunt of arachidonic acid metabolism towards the leukotriene pathway during colonic tumorigenesis promoted by CSE. Suppression of 5-LOX did not induce such a shunt and produced a better response. Therefore, 5-LOX inhibitor is more effective than COX-2 inhibitor, and blocker of both COX-2 and 5-LOX may present a superior anticancer profile in cigarette smokers. © Oxford University Press 2005; all rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/76929
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.439
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYe, YNen_HK
dc.contributor.authorWu, WKKen_HK
dc.contributor.authorShin, VYen_HK
dc.contributor.authorBruce, ICen_HK
dc.contributor.authorWong, BCYen_HK
dc.contributor.authorCho, CHen_HK
dc.date.accessioned2010-09-06T07:26:26Z-
dc.date.available2010-09-06T07:26:26Z-
dc.date.issued2005en_HK
dc.identifier.citationCarcinogenesis, 2005, v. 26 n. 4, p. 827-834en_HK
dc.identifier.issn0143-3334en_HK
dc.identifier.urihttp://hdl.handle.net/10722/76929-
dc.description.abstractPrevious studies indicate that the arachidonic acid-metabolizing enzymes COX-2 and 5-LOX are overexpressed during the process of colonic adenoma formation promoted by cigarette smoke. The aims of the present study were to investigate whether there exists a relationship between COX-2 and 5-LOX, and whether dual inhibition of COX-2 and 5-LOX has an anticarcinogenic effect in the colonic tumorigenesis promoted by cigarette smoke. Results showed that pretreating colon cancer cells with cigarette smoke extract (CSE) promoted colon cancer growth in the nude mouse xenograft model. Inhibition of COX-2 or 5-LOX reduced the tumor size. In the group treated with COX-2-inhibitor, the PGE 2 level decreased while the LTB4 level increased. In contrast, in the 5-LOX-inhibitor treated group, the LTB4 level was reduced and the PGE2 level was unchanged. However, combined treatment with both COX-2 and 5-LOX inhibitors further inhibited the tumor growth promoted by CSE over treatment with either COX-2-inhibitor or 5-LOX-inhibitor alone. This was accompanied by the downregulation of PGE2 and LTB4. In an in vitro study, we found that the action of CSE on colon cancer cells was mediated by 5-LOX DNA demethylation. In summary, these results indicate that inhibition of COX-2 may lead to a shunt of arachidonic acid metabolism towards the leukotriene pathway during colonic tumorigenesis promoted by CSE. Suppression of 5-LOX did not induce such a shunt and produced a better response. Therefore, 5-LOX inhibitor is more effective than COX-2 inhibitor, and blocker of both COX-2 and 5-LOX may present a superior anticancer profile in cigarette smokers. © Oxford University Press 2005; all rights reserved.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_HK
dc.relation.ispartofCarcinogenesisen_HK
dc.rightsCarcinogenesis. Copyright © Oxford University Press.en_HK
dc.subject.meshAdenocarcinoma - enzymology - etiology - prevention & controlen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshApoptosis - drug effectsen_HK
dc.subject.meshArachidonate 5-Lipoxygenase - genetics - metabolismen_HK
dc.subject.meshCell Proliferation - drug effectsen_HK
dc.subject.meshColonic Neoplasms - enzymology - etiology - prevention & controlen_HK
dc.subject.meshCyclooxygenase 2en_HK
dc.subject.meshCyclooxygenase 2 Inhibitorsen_HK
dc.subject.meshCyclooxygenase Inhibitors - therapeutic useen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshDinoprostone - metabolismen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshLeukotriene B4 - metabolismen_HK
dc.subject.meshLipoxygenase Inhibitors - therapeutic useen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred BALB Cen_HK
dc.subject.meshMice, Nudeen_HK
dc.subject.meshNeovascularization, Pathologic - prevention & controlen_HK
dc.subject.meshProstaglandin-Endoperoxide Synthases - drug effects - genetics - metabolismen_HK
dc.subject.meshRNA, Messenger - metabolismen_HK
dc.subject.meshSmoke - adverse effectsen_HK
dc.subject.meshTobaccoen_HK
dc.subject.meshTumor Cells, Cultureden_HK
dc.titleDual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smokeen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0143-3334&volume=26 no 4&spage=827&epage=834&date=2005&atitle=Dual+inhibition+of+5-LOX+and+COX-2+suppresses+colon+cancer+formation+promoted+by+cigarette+smokeen_HK
dc.identifier.emailWong, BCY:bcywong@hku.hken_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/carcin/bgi012en_HK
dc.identifier.pmid15637091en_HK
dc.identifier.scopuseid_2-s2.0-17844390400en_HK
dc.identifier.hkuros97554en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-17844390400&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume26en_HK
dc.identifier.issue4en_HK
dc.identifier.spage827en_HK
dc.identifier.epage834en_HK
dc.identifier.isiWOS:000227976700015-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridYe, YN=7401627402en_HK
dc.identifier.scopusauthoridWu, WKK=18345422600en_HK
dc.identifier.scopusauthoridShin, VY=7003491170en_HK
dc.identifier.scopusauthoridBruce, IC=35612490700en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK
dc.identifier.scopusauthoridCho, CH=7403100461en_HK
dc.identifier.citeulike140069-

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