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- Publisher Website: 10.1016/j.taap.2008.08.012
- Scopus: eid_2-s2.0-56049099971
- PMID: 18805435
- WOS: WOS:000261477900011
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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
Title | 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 | ||||
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Authors | |||||
Keywords | β-adrenergic receptor COX-2 Nicotine Nicotinic acetylcholine receptor NNK | ||||
Issue Date | 2008 | ||||
Publisher | Academic 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? | ||||
Abstract | Induction 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 Identifier | http://hdl.handle.net/10722/92113 | ||||
ISSN | 2023 Impact Factor: 3.3 2023 SCImago Journal Rankings: 0.788 | ||||
ISI Accession Number ID |
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 Field | Value | Language |
---|---|---|
dc.contributor.author | Shin, VY | en_HK |
dc.contributor.author | Jin, HC | en_HK |
dc.contributor.author | Ng, EKO | en_HK |
dc.contributor.author | Yu, J | en_HK |
dc.contributor.author | Leung, WK | en_HK |
dc.contributor.author | Cho, CH | en_HK |
dc.contributor.author | Sung, JJY | en_HK |
dc.date.accessioned | 2010-09-17T10:36:28Z | - |
dc.date.available | 2010-09-17T10:36:28Z | - |
dc.date.issued | 2008 | en_HK |
dc.identifier.citation | Toxicology And Applied Pharmacology, 2008, v. 233 n. 2, p. 254-261 | en_HK |
dc.identifier.issn | 0041-008X | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/92113 | - |
dc.description.abstract | Induction 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.language | eng | en_HK |
dc.publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/locate/taap | en_HK |
dc.relation.ispartof | Toxicology and Applied Pharmacology | en_HK |
dc.subject | β-adrenergic receptor | en_HK |
dc.subject | COX-2 | en_HK |
dc.subject | Nicotine | en_HK |
dc.subject | Nicotinic acetylcholine receptor | en_HK |
dc.subject | NNK | en_HK |
dc.subject.mesh | Adenocarcinoma - metabolism | en_HK |
dc.subject.mesh | Bungarotoxins - pharmacology | en_HK |
dc.subject.mesh | Carcinogens - toxicity | en_HK |
dc.subject.mesh | Cell Line, Tumor | en_HK |
dc.subject.mesh | Cell Proliferation - drug effects | en_HK |
dc.subject.mesh | Cyclin D1 - metabolism | en_HK |
dc.subject.mesh | Cyclooxygenase 2 - drug effects - metabolism | en_HK |
dc.subject.mesh | Dinoprostone - metabolism | en_HK |
dc.subject.mesh | Gene Expression Regulation - drug effects | en_HK |
dc.subject.mesh | Humans | en_HK |
dc.subject.mesh | Nicotine - toxicity | en_HK |
dc.subject.mesh | Nitrosamines - toxicity | en_HK |
dc.subject.mesh | Propranolol - pharmacology | en_HK |
dc.subject.mesh | Receptors, Adrenergic, beta - drug effects - metabolism | en_HK |
dc.subject.mesh | Receptors, Nicotinic - drug effects - metabolism | en_HK |
dc.subject.mesh | Signal Transduction - drug effects | en_HK |
dc.subject.mesh | Stomach Neoplasms - metabolism | en_HK |
dc.subject.mesh | p38 Mitogen-Activated Protein Kinases - drug effects - metabolism | en_HK |
dc.title | 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 | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Ng, EKO: ngko@hku.hk | en_HK |
dc.identifier.email | Leung, WK: waikleung@hku.hk | en_HK |
dc.identifier.authority | Ng, EKO=rp01364 | en_HK |
dc.identifier.authority | Leung, WK=rp01479 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.taap.2008.08.012 | en_HK |
dc.identifier.pmid | 18805435 | - |
dc.identifier.scopus | eid_2-s2.0-56049099971 | en_HK |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-56049099971&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 233 | en_HK |
dc.identifier.issue | 2 | en_HK |
dc.identifier.spage | 254 | en_HK |
dc.identifier.epage | 261 | en_HK |
dc.identifier.eissn | 1096-0333 | - |
dc.identifier.isi | WOS:000261477900011 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.scopusauthorid | Shin, VY=7003491170 | en_HK |
dc.identifier.scopusauthorid | Jin, HC=24577511700 | en_HK |
dc.identifier.scopusauthorid | Ng, EKO=21135553700 | en_HK |
dc.identifier.scopusauthorid | Yu, J=35351306800 | en_HK |
dc.identifier.scopusauthorid | Leung, WK=7201504523 | en_HK |
dc.identifier.scopusauthorid | Cho, CH=14067000400 | en_HK |
dc.identifier.scopusauthorid | Sung, JJY=35405352400 | en_HK |
dc.identifier.issnl | 0041-008X | - |