title: The modulating role of nuclear factor-kappaB in the action of alpha7-nicotinic acetylcholine receptor and cross-talk between 5-lipoxygenase and cyclooxygenase-2 in colon cancer growth induced by 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone.
abstract: 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the tobacco-specific nitrosamine, induces lung cancer in all animal species tested and is thought to contribute significantly to the high lung cancer burden associated with smoking. However, there is no report whether NNK could promote colon cancer growth. To address this hypothesis and the possible signaling pathways involved, we used SW1116 colon cancer cell line to study these biological events in vitro. Results showed that NNK, after 5-h treatment, stimulated cell proliferation, enhanced alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) mRNA levels and nuclear factor-kappaB (NF-kappaB) DNA binding activity, as well as 5-lipoxygenase and cyclooxygenase-2 protein expressions. alpha-Bungarotoxin, the specific alpha7-nAChR antagonist, inhibited these biological effects. However, 5-lipoxygenase inhibition had no effect on alpha7-nAChR mRNA expression, but significantly inhibited cell proliferation and activation of NF-kappaB and cyclooxygenase-2, whereas NF-kappaB-specific inhibitor caffeic acid phenethyl ester reduced both cell proliferation and cyclooxygenase expression induced by NNK without affecting alpha7-nAChR mRNA level and 5-lipoxygenase expression. Together, the present study demonstrated that NNK promoted colon cancer growth in vitro. NF-kappaB not only conveys the biological effect of alpha7-nAChR activation but is also involved in the cross-talk between 5-lipoxygenase and cyclooxygenase-2 in response to NNK in colon cancer cell development.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 1/F Li Shu Fan Bldg., 5 Sassoon Rd., Hong Kong, China.
authors.forename: Yi N
authors.initials: YN
authors.lastname: Ye
authors.forename: Edgar S L
authors.initials: ES
authors.lastname: Liu
authors.forename: Vivian Y
authors.initials: VY
authors.lastname: Shin
authors.forename: William K K
authors.initials: WK
authors.lastname: Wu
authors.forename: Chi H
authors.initials: CH
authors.lastname: Cho
mesh_terms: D002038:Bungarotoxins / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism*; D008565:Membrane Proteins; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009602:Nitrosamines / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D002038:Bungarotoxins; D002273:Carcinogens; C579167:Chrna7 protein, human; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D018733:Nicotinic Antagonists; D009602:Nitrosamines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D004247:DNA; D008084:Lipoxygenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases