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Article: Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine receptor (nAChR) and β-adrenergic receptor signaling pathways

TitleNicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine receptor (nAChR) and β-adrenergic receptor signaling pathways
Authors
Keywordsβ-adrenergic receptor
COX-2
Nicotine
Nicotinic acetylcholine receptor
NNK
Issue Date2008
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/taap
Citation
Toxicology And Applied Pharmacology, 2008, v. 233 n. 2, p. 254-261 How to Cite?
AbstractInduction of cyclooxygenase-2 (COX-2) associates with cigarette smoke exposure in many malignancies. Nicotine and its derivative, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are the two important components in cigarette smoke that contributes to cancer development. However, the molecular mechanism(s) by which nicotine or NNK promotes gastric carcinogenesis remains largely unknown. We found that nicotine and NNK significantly enhanced cell proliferation in AGS cells that expressed both alpha7 nicotinic acetylcholine receptor (α7 nAChR) and β-adrenergic receptors. Treatment of cells with α-bungarotoxin (α-BTX, α7nAChR antagonist) or propranolol (β-adrenergic receptor antagonist) blocked NNK-induced COX-2/PGE2 and cell proliferation, while nicotine-mediated cell growth and COX-2/PGE2 induction can only be suppressed by propranolol, but not α-BTX. Moreover, in contrast to the dependence of growth promoting effect of nicotine on Erk activation, inhibitor of p38 mitogen-activated protein kinase (MAPK) repressed NNK-induced COX-2 upregulation and resulted in suppression of cell growth. In addition, nicotine and NNK mediated COX-2 induction via different receptors to modulate several G1/S transition regulatory proteins and promote gastric cancer cell growth. Selective COX-2 inhibitor (SC-236) caused G1 arrest and abrogated nicotine/NNK-induced cell proliferation. Aberrant expression of cyclin D1 and other G1 regulatory proteins are reversed by blockade of COX-2. These results pointed to the importance of adrenergic and nicotinic receptors in gastric tumor growth through MAPK/COX-2 activation, which may perhaps provide a chemoprevention strategy for cigarette smoke-related gastric carcinogenesis. © 2008 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/92113
ISSN
2015 Impact Factor: 3.847
2015 SCImago Journal Rankings: 1.593
ISI Accession Number ID
Funding AgencyGrant Number
Chinese University of Hong Kong2041341
Funding Information:

We are grateful to Mr. Wallace So for his excellent technical assistance. This work was partly Supported by a grant from The Chinese University of Hong Kong direct grant (No. 2041341).

References

 

DC FieldValueLanguage
dc.contributor.authorShin, VYen_HK
dc.contributor.authorJin, HCen_HK
dc.contributor.authorNg, EKOen_HK
dc.contributor.authorYu, Jen_HK
dc.contributor.authorLeung, WKen_HK
dc.contributor.authorCho, CHen_HK
dc.contributor.authorSung, JJYen_HK
dc.date.accessioned2010-09-17T10:36:28Z-
dc.date.available2010-09-17T10:36:28Z-
dc.date.issued2008en_HK
dc.identifier.citationToxicology And Applied Pharmacology, 2008, v. 233 n. 2, p. 254-261en_HK
dc.identifier.issn0041-008Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/92113-
dc.description.abstractInduction of cyclooxygenase-2 (COX-2) associates with cigarette smoke exposure in many malignancies. Nicotine and its derivative, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are the two important components in cigarette smoke that contributes to cancer development. However, the molecular mechanism(s) by which nicotine or NNK promotes gastric carcinogenesis remains largely unknown. We found that nicotine and NNK significantly enhanced cell proliferation in AGS cells that expressed both alpha7 nicotinic acetylcholine receptor (α7 nAChR) and β-adrenergic receptors. Treatment of cells with α-bungarotoxin (α-BTX, α7nAChR antagonist) or propranolol (β-adrenergic receptor antagonist) blocked NNK-induced COX-2/PGE2 and cell proliferation, while nicotine-mediated cell growth and COX-2/PGE2 induction can only be suppressed by propranolol, but not α-BTX. Moreover, in contrast to the dependence of growth promoting effect of nicotine on Erk activation, inhibitor of p38 mitogen-activated protein kinase (MAPK) repressed NNK-induced COX-2 upregulation and resulted in suppression of cell growth. In addition, nicotine and NNK mediated COX-2 induction via different receptors to modulate several G1/S transition regulatory proteins and promote gastric cancer cell growth. Selective COX-2 inhibitor (SC-236) caused G1 arrest and abrogated nicotine/NNK-induced cell proliferation. Aberrant expression of cyclin D1 and other G1 regulatory proteins are reversed by blockade of COX-2. These results pointed to the importance of adrenergic and nicotinic receptors in gastric tumor growth through MAPK/COX-2 activation, which may perhaps provide a chemoprevention strategy for cigarette smoke-related gastric carcinogenesis. © 2008 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/taapen_HK
dc.relation.ispartofToxicology and Applied Pharmacologyen_HK
dc.subjectβ-adrenergic receptoren_HK
dc.subjectCOX-2en_HK
dc.subjectNicotineen_HK
dc.subjectNicotinic acetylcholine receptoren_HK
dc.subjectNNKen_HK
dc.subject.meshAdenocarcinoma - metabolismen_HK
dc.subject.meshBungarotoxins - pharmacologyen_HK
dc.subject.meshCarcinogens - toxicityen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshCell Proliferation - drug effectsen_HK
dc.subject.meshCyclin D1 - metabolismen_HK
dc.subject.meshCyclooxygenase 2 - drug effects - metabolismen_HK
dc.subject.meshDinoprostone - metabolismen_HK
dc.subject.meshGene Expression Regulation - drug effectsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshNicotine - toxicityen_HK
dc.subject.meshNitrosamines - toxicityen_HK
dc.subject.meshPropranolol - pharmacologyen_HK
dc.subject.meshReceptors, Adrenergic, beta - drug effects - metabolismen_HK
dc.subject.meshReceptors, Nicotinic - drug effects - metabolismen_HK
dc.subject.meshSignal Transduction - drug effectsen_HK
dc.subject.meshStomach Neoplasms - metabolismen_HK
dc.subject.meshp38 Mitogen-Activated Protein Kinases - drug effects - metabolismen_HK
dc.titleNicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine receptor (nAChR) and β-adrenergic receptor signaling pathwaysen_HK
dc.typeArticleen_HK
dc.identifier.emailNg, EKO: ngko@hku.hken_HK
dc.identifier.emailLeung, WK: waikleung@hku.hken_HK
dc.identifier.authorityNg, EKO=rp01364en_HK
dc.identifier.authorityLeung, WK=rp01479en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.taap.2008.08.012en_HK
dc.identifier.pmid18805435-
dc.identifier.scopuseid_2-s2.0-56049099971en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-56049099971&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume233en_HK
dc.identifier.issue2en_HK
dc.identifier.spage254en_HK
dc.identifier.epage261en_HK
dc.identifier.eissn1096-0333-
dc.identifier.isiWOS:000261477900011-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridShin, VY=7003491170en_HK
dc.identifier.scopusauthoridJin, HC=24577511700en_HK
dc.identifier.scopusauthoridNg, EKO=21135553700en_HK
dc.identifier.scopusauthoridYu, J=35351306800en_HK
dc.identifier.scopusauthoridLeung, WK=7201504523en_HK
dc.identifier.scopusauthoridCho, CH=14067000400en_HK
dc.identifier.scopusauthoridSung, JJY=35405352400en_HK

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