Cellular and molecular mechanisms of nicotine's pro-angiogenesis activity and its potential impact on cancer.
The present study examined the mechanisms of nicotine's effect on angiogenesis and its impact on tumor growth. Nicotine demonstrated significant (P<0.01) stimulation of the release of endothelial cell growth factor, basic fibroblast growth factor (b-FGF) but not vascular endothelial growth factor (VEGF). In a concentration-dependent manner, nicotine induced endothelial cell tube formation. Additionally, in the chick chorioallantoic membrane (CAM) model of angiogenesis, nicotine effectively induced the generation of new blood vessels (P<0.01), an effect that is mediated via b-FGF. The pro-angiogenesis effect of nicotine in the CAM model was maximally blocked by either anti-integrin alphavbeta3 or inhibitor of mitogen activated protein kinase (MAPK, ERK 1/2). In the CAM tumor implant model, nicotine doubled (P<0.01) the growth rate of breast, colon, and lung cancer. These data indicated that the pro-angiogenesis effect is mediated via b-FGF and induced through the nicotinic receptor, alphavbeta3 integrin, and MAPK.
Mousa
Sarah
S
Pharmaceutical Research Institute, Albany College of Pharmacy, Albany, New York 12208, USA.
Mousa
Shaker A
SA
D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D008297:Male; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D009538:Nicotine