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

Abstract

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.

• Authors: Yi-Ni Ye, Edgar Shiu-Lam Liu, Vivian Yvonne Shin, William Ka-Kei Wu, Chi-Hin Cho
• Journal: Toxicology (Toxicology) Vol. 203 Issue 1-3 Pg. 179-88 (Oct 15 2004) ISSN: 0300-483X [Print] Ireland
• PMID: 15363593 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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