Lipoxygenase expression in colon polyps and inhibition of colon cancer growth by lipoxygenase blockade

Abstract

Abstract Introduction: Expression of 5-lipoxygenase (5-LOX) has been shown to be up-regulated in early pancreatic cancer, but has not been characterized in early colon neoplasms. We hypothesize that there is upregulation of 5-LOX in colon polyps and that inhibition of 5-LOX in colon cancer cell lines would inhibit cell growth and induce apoptosis. Methods: Tissue samples of normal colonic mucosa and neoplastic polyps were collected from 20 patients. Immunohistochemistry was used to compare 5-LOX expression between patient's normal colonic mucosa and polyps. Effects of the specific 5-LOX inhibitor, Rev 5901, on cell proliferation were studied in 3 colon cancer cell lines (LoVo, HT-29, HCT-116). Results: Intense 5-LOX staining was evident in polyps from 20/20 specimens. Adjacent areas of normal colonic mucosa did not express 5-LOX. Specific 5-LOX blockade with Rev 5901 showed concentration and time-dependent inhibition of cell proliferation (85% reduction relative to control with 15uM at 24 hours, p Conclusions: These results demonstrate that 1) 5-LOX is up-regulated in colon polyps compared to normal mucosa, and 2) treatment with 5-LOX inhibitor Rev 5901 results in decreased cell proliferation and increased apoptosis. These findings provide evidence that 5-LOX plays a role in colon cancer development and may be an early target for chemoprevention of colon cancer.