Contributory role of 5-lipoxygenase and its association with angiogenesis in the promotion of inflammation-associated colonic tumorigenesis by cigarette smoking

Toxicology. 2004 Oct 15;203(1-3):179-88. doi: 10.1016/j.tox.2004.06.004.


Our previous study shows that cigarette smoking can promote inflammation-associated adenoma formation in the mouse colon, but the underlying mechanism remains unknown. Several studies suggest that there is a link between 5-lipoxygenase (5-LOX) and carcinogenesis in humans and animals. In the present study, we aims to investigate whether the promoting action of cigarette smoke on inflammation-associated colon cancer formation is associated with 5-LOX activation in mice. Results showed that exposure to the mainstream smoke of unfiltered cigarettes enhanced the 5-LOX protein expression in the inflammation-associated colonic adenomas. It was accompanied with an up-regulation of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF). Both are the key angiogenic factors for tumorigenesis. 5-LOX inhibitors decreased the incidence of colonic adenoma formation and reduced angiogenesis, MMP-2 activity and VEGF protein expression in the colons of these animals. Taken together, these results strongly suggest that cigarette smoke can induce 5-LOX expression which plays an important role in activation of MMP-2 and VEGF to induce angiogenic process and promotion of inflammation-associated adenoma formation in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / etiology
  • Adenoma / pathology*
  • Animals
  • Arachidonate 5-Lipoxygenase / biosynthesis
  • Arachidonate 5-Lipoxygenase / physiology*
  • Blotting, Western
  • Colitis, Ulcerative / chemically induced
  • Colonic Neoplasms / etiology
  • Colonic Neoplasms / pathology*
  • Dextrans
  • Enzyme Inhibitors / pharmacology
  • Inflammation / etiology
  • Inflammation / pathology*
  • Intestinal Mucosa / pathology
  • Lipoxygenase Inhibitors
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Smoking / metabolism
  • Smoking / pathology*
  • Vascular Endothelial Growth Factor A / biosynthesis


  • Dextrans
  • Enzyme Inhibitors
  • Lipoxygenase Inhibitors
  • Vascular Endothelial Growth Factor A
  • Arachidonate 5-Lipoxygenase
  • Matrix Metalloproteinase 2