title: Nicotine stimulates proliferation and inhibits apoptosis in colon cancer cell lines through activation of survival pathways.
abstract: 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.
  
  
  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.affiliation: Department of Surgery Pietro Valdoni, Sapienza University of Rome, Rome, Italy. alessandra.cucina@uniroma1.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cucina
authors.forename: Simona
authors.initials: S
authors.lastname: Dinicola
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Coluccia
authors.forename: Sara
authors.initials: S
authors.lastname: Proietti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: D'Anselmi
authors.forename: Alessia
authors.initials: A
authors.lastname: Pasqualato
authors.forename: Mariano
authors.initials: M
authors.lastname: Bizzarri
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002038:Bungarotoxins / Q000494:pharmacology; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D000077022:Survivin; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C107489:BIRC5 protein, human; D002038:Bungarotoxins; C579167:Chrna7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D018722:Nicotinic Agonists; D019253:Proto-Oncogene Proteins c-bcl-2; D011978:Receptors, Nicotinic; D000077022:Survivin; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D011493:Protein Kinase C