RT Journal Article
SR Electronic
T1 The Modulating Role of Nuclear Factor-κB in the Action of α7-Nicotinic Acetylcholine Receptor and Cross-Talk between 5-Lipoxygenase and Cyclooxygenase-2 in Colon Cancer Growth Induced by 4-(<em>N</em>-Methyl-<em>N</em>-nitrosamino)-1-(3-pyridyl)-1-butanone
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 123
OP 130
DO 10.1124/jpet.104.068031
VO 311
IS 1
A1 Yi N. Ye
A1 Edgar S. L. Liu
A1 Vivian Y. Shin
A1 William K. K. Wu
A1 Chi H. Cho
YR 2004
UL http://jpet.aspetjournals.org/content/311/1/123.abstract
AB 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 α7-nicotinic acetylcholine receptor (α7-nAChR) mRNA levels and nuclear factor-κB (NF-κB) DNA binding activity, as well as 5-lipoxygenase and cyclooxygenase-2 protein expressions. α-Bungarotoxin, the specific α7-nAChR antagonist, inhibited these biological effects. However, 5-lipoxygenase inhibition had no effect on α7-nAChR mRNA expression, but significantly inhibited cell proliferation and activation of NF-κB and cyclooxygenase-2, whereas NF-κB-specific inhibitor caffeic acid phenethyl ester reduced both cell proliferation and cyclooxygenase expression induced by NNK without affecting α7-nAChR mRNA level and 5-lipoxygenase expression. Together, the present study demonstrated that NNK promoted colon cancer growth in vitro. NF-κB not only conveys the biological effect of α7-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. The American Society for Pharmacology and Experimental Therapeutics