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

Ashraful Hoque, Scott M. Lippman, Tsung Teh Wu, Ya Xu, Zheng D. Liang, Stephen Swisher, Hongfu Zhang, Liyu Cao, Jaffer A. Ajani, Xiao Chun Xu

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98 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)785-791
Number of pages7
JournalCarcinogenesis
Volume26
Issue number4
DOIs
StatePublished - Sep 6 2005

ASJC Scopus subject areas

  • Cancer Research

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    Hoque, A., Lippman, S. M., Wu, T. T., Xu, Y., Liang, Z. D., Swisher, S., Zhang, H., Cao, L., Ajani, J. A., & Xu, X. C. (2005). Increased 5-lipoxygenase expression and induction of apoptosis by its inhibitors in esophageal cancer: A potential target for prevention. Carcinogenesis, 26(4), 785-791. https://doi.org/10.1093/carcin/bgi026