Nicotine promotes cell proliferation via alpha7-nicotinic acetylcholine receptor and catecholamine-synthesizing enzymes-mediated pathway in human colon adenocarcinoma HT-29 cells

Toxicol Appl Pharmacol. 2007 Jun 15;221(3):261-7. doi: 10.1016/j.taap.2007.04.002. Epub 2007 Apr 12.


Cigarette smoking has been implicated in colon cancer. Nicotine is a major alkaloid in cigarette smoke. In the present study, we showed that nicotine stimulated HT-29 cell proliferation and adrenaline production in a dose-dependent manner. The stimulatory action of nicotine was reversed by atenolol and ICI 118,551, a beta(1)- and beta(2)-selective antagonist, respectively, suggesting the role of beta-adrenoceptors in mediating the action. Nicotine also significantly upregulated the expression of the catecholamine-synthesizing enzymes [tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DbetaH) and phenylethanolamine N-methyltransferase]. Inhibitor of TH, a rate-limiting enzyme in the catecholamine-biosynthesis pathway, reduced the actions of nicotine on cell proliferation and adrenaline production. Expression of alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) was demonstrated in HT-29 cells. Methyllycaconitine, an alpha7-nAChR antagonist, reversed the stimulatory actions of nicotine on cell proliferation, TH and DbetaH expression as well as adrenaline production. Taken together, through the action on alpha7-nAChR nicotine stimulates HT-29 cell proliferation via the upregulation of the catecholamine-synthesis pathway and ultimately adrenaline production and beta-adrenergic activation. These data reveal the contributory role alpha7-nAChR and beta-adrenoceptors in the tumorigenesis of colon cancer cells and partly elucidate the carcinogenic action of cigarette smoke on colon cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Alkaloids / metabolism
  • Alkaloids / pharmacology*
  • Cell Proliferation / drug effects*
  • Colonic Neoplasms / metabolism*
  • Dopamine beta-Hydroxylase / drug effects
  • Dopamine beta-Hydroxylase / metabolism
  • Dose-Response Relationship, Drug
  • Epinephrine / metabolism*
  • Humans
  • Nicotine / metabolism
  • Nicotine / pharmacology*
  • Nicotinic Agonists / metabolism
  • Nicotinic Agonists / pharmacology
  • Phenylethanolamine N-Methyltransferase / drug effects
  • Phenylethanolamine N-Methyltransferase / metabolism
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / metabolism
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured
  • Tyrosine 3-Monooxygenase / drug effects
  • Tyrosine 3-Monooxygenase / metabolism
  • Up-Regulation
  • alpha7 Nicotinic Acetylcholine Receptor


  • Alkaloids
  • Chrna7 protein, human
  • Nicotinic Agonists
  • Receptors, Adrenergic, beta
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • Nicotine
  • Tyrosine 3-Monooxygenase
  • Dopamine beta-Hydroxylase
  • Phenylethanolamine N-Methyltransferase
  • Epinephrine