Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Dec;29(4):723-35.
doi: 10.1007/s10555-010-9264-x.

Cytochrome P450-derived eicosanoids: the neglected pathway in cancer

Dipak Panigrahy  1 , Arja Kaipainen, Emily R Greene, Sui Huang
Affiliations
Review

Cytochrome P450-derived eicosanoids: the neglected pathway in cancer

Dipak Panigrahy et al. Cancer Metastasis Rev. 2010 Dec.

Abstract

Endogenously produced lipid autacoids are locally acting small molecule mediators that play a central role in the regulation of inflammation and tissue homeostasis. A well-studied group of autacoids are the products of arachidonic acid metabolism, among which the prostaglandins and leukotrienes are the best known. They are generated by two pathways controlled by the enzyme systems cyclooxygenase and lipoxygenase, respectively. However, arachidonic acid is also substrate for a third enzymatic pathway, the cytochrome P450 (CYP) system. This third eicosanoid pathway consists of two main branches: ω-hydroxylases convert arachidonic acid to hydroxyeicosatetraenoic acids (HETEs) and epoxygenases convert it to epoxyeicosatrienoic acids (EETs). This third CYP pathway was originally studied in conjunction with inflammatory and cardiovascular disease. Arachidonic acid and its metabolites have recently stimulated great interest in cancer biology; but, unlike prostaglandins and leukotrienes the link between cytochome P450 metabolites and cancer has received little attention. In this review, the emerging role in cancer of cytochrome P450 metabolites, notably 20-HETE and EETs, are discussed.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
a, b Bioactive eicosanoids derived from the arachidonic acid cascade. Arachidonic acid is metabolized by three pathways—the cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) pathways. Schematic overview of major mediators and their metabolites (blue); enzymes (black, boxed) and biological role (green). Inhibitors (red ovals) and agonists (green ovals). HETEs Hydroxyeicosatetraenoic acids, EETs epoxyeicosatrienoic acids, CYP cytochrome P450 enzymes. MS-PPOH is a selective inhibitor of a subset of epoxygenases. HET0016 is a selective inhibitor of the ω-hydroxlase CYP4A. The sEH inhibitor (soluble epoxide hydrolase inhibitor) increases EET levels by acting as an agonist of the EET pathway. 14,15-EEZE is a putative EET receptor antagonist. PGE 2 prostaglandin E2, PGI 2 prostacyclin, LTA 4 leukotriene A4, DHET dihydroxyeicosatrienoic acid, 20-OH PGE 2 20-hydroxy-prostaglandin E2
Fig. 2
Fig. 2
Cytochrome P450 epoxygenase expression in tumor cell compartments and their potential role in cell–cell communication in the tumor stroma. Note that both tumor cells and endothelial cell can produce EETs (blue circles), establishing an autocatalytic loop. EETs may act in an autocrine or paracrine fashion
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Zeldin DC. Epoxygenase pathways of arachidonic acid metabolism. The Journal of Biological Chemistry. 2001;276:36059–36062. - PubMed
    1. Imig JD, Hammock BD. Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nature Reviews. Drug Discovery. 2009;8:794–805. - PMC - PubMed
    1. Wang D, Dubois RN. Eicosanoids and cancer. Nature Reviews. Cancer. 2010;10:181–193. - PMC - PubMed
    1. Roman RJ. P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiological Reviews. 2002;82:131–185. - PubMed
    1. Fleming I. Epoxyeicosatrienoic acids, cell signaling and angiogenesis. Prostaglandins & Other Lipid Mediators. 2007;82:60–67. - PubMed

Publication types

MeSH terms

LinkOut - more resources

-