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Carcinogenesis. 2005 Apr;26(4):785-91. Epub 2005 Jan 20.

Increased 5-lipoxygenase expression and induction of apoptosis by its inhibitors in esophageal cancer: a potential target for prevention.

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  • 1Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Abstract

Arachidonic acid (AA) is the major precursor of several classes of signal molecules and the alteration of its metabolism is involved in human carcinogenesis. For instance, 5-lipoxygenase (5-LOX) converts AA to hydroxyeicosatetraenoic acids or leukotrienes (LTs), which are able to enhance proliferation, increase survival and suppress the apoptosis of human cells. To determine the potential use of 5-LOX inhibitors in the prevention of esophageal cancer, we first analyzed the 5-LOX expression in esophageal tissue samples using immunohistochemistry and then examined the effect of the 5-LOX inhibitors AA861 and REV5901 on cell viability and apoptosis in esophageal cancer cell lines. 5-LOX expression was present in 79% (127/161) of esophageal cancer but in only 13% (4/32) of normal esophageal mucosa. 5-LOX was also expressed in all the eight esophageal cancer cell lines. Moreover, 5-LOX inhibitors caused a dose- and time-dependent reduction of cell viability, which was due to the induction of apoptosis and associated with LTB4 suppression. Our data also showed that both LTB4, a product of 5-LOX and LTB4 receptor antagonist U-75302 were able to prevent AA861 and REV5901 on induction of apoptosis. The present study demonstrated that 5-LOX protein expression is increased in esophageal cancer and that 5-LOX inhibitors can induce esophageal cancer cells to undergo apoptosis, suggesting that 5-LOX may be an effective target in the prevention of esophageal cancer.

PMID:
15661803
[PubMed - indexed for MEDLINE]
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