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Nicotine stimulates proliferation and inhibits apoptosis in colon cancer cell lines through activation of survival pathways.
MedLine Citation:
PMID:  22520577     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Colorectal cancer is one of the leading causes of cancer-related death throughout the world, and the risk to develop this malignant disease seems to be associated with long-term cigarette smoking. Nicotine, one of the major components of cigarette smoking, can stimulate cell proliferation and suppress apoptosis both in normal cells and in several human cancer cell lines derived from various organs. However, although nicotine appears to have a role in stimulating cell proliferation of colon cancer cells, there is no information on its role in inhibiting apoptosis in these cells. MATERIALS AND METHODS: Human colorectal cancer cell lines Caco-2 and HCT-8 were treated with 1 μM nicotine alone or in combination with 1 μM α-BTX in complete or in serum free medium. Cell proliferation and apoptosis were determined by cell count performed with a cell counter and by cytofluorimetric assay respectively. PI3K/Akt and PKC/ERK1/2 pathways, survivin, and P-Bcl2 (Ser70) were investigated by Western blot analysis. RESULTS: Nicotine induced an increase in cell proliferation and a decrease of apoptosis in Caco-2 and HCT-8 cells. Both cell growth and apoptosis appear to be mediated by α7-nicotinic acetylcholine receptors, since treatment with α-Bungarotoxin inhibited these processes. Nicotine induced a statistically significant increase in the expression of PI3K and in P-Akt/Akt ratio as well as in the expression of PKC, ERK1/2, survivin, and P-Bcl2 (Ser70) in both cell lines. CONCLUSIONS: Nicotine, contained in cigarette smoking, could participate in colon cancer development and progression by stimulating cell proliferation and suppressing physiological apoptosis.
Authors:
Alessandra Cucina; Simona Dinicola; Pierpaolo Coluccia; Sara Proietti; Fabrizio D'Anselmi; Alessia Pasqualato; Mariano Bizzarri
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-10
Journal Detail:
Title:  The Journal of surgical research     Volume:  -     ISSN:  1095-8673     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-4-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Surgery Pietro Valdoni, Sapienza University of Rome, Rome, Italy.
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