Epoxyeicosatrienoic acids and soluble epoxide hydrolase: Potential therapeutic targets for inflammation and its induced carcinogenesis

Stephanie Norwood, Jie Liao, Bruce D. Hammock, Guang Yu Yang

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Chronic inflammation is an important factor contributing to human carcinoma, and non-steroidal antiinflammatory drugs (NSAIDs) have been shown to have a preventive effect in the development of various types of carcinoma. However, NSAIDs also have adverse side effects including increased cardiovascular events, making them less than ideal for routine chemoprevention. Soluble epoxide hydrolase (sEH) is an enzyme that converts endogenous anti-inflammatory compounds, the epoxyeicosatrienoic acids (EETs), to the less anti-inflammatory dihydroxyeicosatrienoic acids (DHETs). Inhibition of sEH, by a highly selective and potent sEH inhibitor (sEHI), increases EETs leading to decreased inflammation. In our studies, administration of a sEHI in mouse colitis models led to decreased ulcer incidence and number of ulcers compared to controls, with no adverse side effects seen. In human tissue, sEH showed an increase in expression, as seen immunohistochemically, in ulcerative colitis (UC), UC-induced dysplasia, and UCinduced carcinoma. Thus, inhibition of sEH may be a novel biomarker and potential therapeutic target in inflammation and inflammation-induced carcinoma.

Original languageEnglish (US)
Pages (from-to)447-457
Number of pages11
JournalAmerican Journal of Translational Research
Volume2
Issue number4
StatePublished - 2010

Keywords

  • Cancer
  • Carcinogenesis
  • Dihydroxyeicosatrienoic acids (DHETs)
  • Epoxyeicosatrienoic acids (EETs)
  • Inflammation
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Soluble epoxide hydrolase (sEH)
  • Therapy

ASJC Scopus subject areas

  • Medicine(all)
  • Cancer Research
  • Clinical Biochemistry
  • Molecular Medicine

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