15-HETE is the main eicosanoid formed by human colonic mucosa

Zijlstra, Freek J.; Dijk, A. P. M. van; Wilson, J. H. P.; Riemsdijk-overbeeke, I. C. van; Vincent, J.; Ouwendijk, Rob J.

doi:10.1007/bf01991025

Cited by 12 publications

(11 citation statements)

References 22 publications

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“…In human colonic mucosa, reported 15-HETE levels were between 2- and 100-fold higher than 12-HETE, with 5-HETE being present at much lower concentrations (7, 19, 34, 35). These species differences are likely due in part to the fact that 12- S and 15- S -HETEs are produced by a 12/15-LOX in rodents (which produces mainly 12-HETE), whereas they are produced by two distinct enzymes in humans (36, 37).…”

Section: Discussionmentioning

confidence: 97%

“…The target for cancer prevention, however, is normal colon. For studying early changes, it therefore may be more pertinent to evaluate the role of eicosanoids that are characteristically higher in normal than tumor tissue, such as the lipoxygenase (LOX) product 15- S -hydroxyeicosatetraenoic acid (HETE) (4-7). LOXs convert arachidonic acid to 5-, 12-, and 15- S -HETEs (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Compared to normal mucosa, transformed mucosa has reduced 15-LOX and increased 5- and 12-LOX expression (6, 7, 13-15). 15-HETE appears to have protective and anti-inflammatory activities, while 5- and 12-HETEs are thought to be pro-inflammatory (16-18).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Fish Oil on Levels ofR- andS-Enantiomers of 5-, 12-, and 15-Hydroxyeicosatetraenoic Acids in Mouse Colonic Mucosa

Neilson

Ren

Hong

et al. 2012

Nutrition and Cancer

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The balance of putative pro- and anti-inflammatory lipoxygenase (LOX)-derived S-hydroxyeicosatetraenoic acids (S-HETEs) in colon mucosa is a potential target for modulating colon cancer risk and progression. The biological effects of S-HETEs and R-HETEs (produced by distinct pathways) may differ, but levels of these compounds in colon are unknown. The objective of this study was to develop chiral methods to characterize HETE enantiomers in colonic mucosa and evaluate the effects of fish oil on HETE formation. C57BL/6 mice (COX-1 null, COX-2 null, wild-type) were fed a diet supplemented with either olive oil or menhaden oil for 11 weeks, and R/S-HETEs in colonic mucosa were quantified by chiral LC-MS/MS. The R-enantiomer comprised 60-72% of 5-HETE, 18-58% of 15-HETE and 1-16% of 12-HETE in colonic mucosa, suggesting that non-LOX sources contribute to HETE profiles. Fish oil reduced levels of both R- and S-HETEs, and increased the preponderance of the R-enantiomers (particularly 12- and 15-HETEs). There was apparent shunting of arachidonic acid to12/15-LOX in the COX-1 null animals. This is the first report of the enantiomeric composition of HETEs in the colon in vivo.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Effect of Fish Oil on Levels ofR- andS-Enantiomers of 5-, 12-, and 15-Hydroxyeicosatetraenoic Acids in Mouse Colonic Mucosa

Neilson

Ren

Hong

et al. 2012

Nutrition and Cancer

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“…15‐LOX‐1, on the other hand, is able to metabolize arachidonic acid and linoleic acid to 15S‐HETE and 13S‐HODE, respectively. Although 15‐LOX‐2 is not expressed in human colon,32 15S‐HETE is the main eicosanoid formed in noncancer colonic mucosa 35. There are conflicting reports regarding the expression of 15‐LOX‐1 in human colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

15‐hydroxy‐eicosatetraenoic acid arrests growth of colorectal cancer cells via a peroxisome proliferator‐activated receptor gamma‐dependent pathway

Chen

Lee

et al. 2003

Intl Journal of Cancer

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Peroxisome proliferator-activated receptor gamma (PPAR␥) inhibits cell growth via promoting apoptosis. Human colorectal cancer tissues had abundant PPAR␥ but the incidence of apoptosis was very low, suggesting a defect in the PPAR␥ pathway. Here, we found that 15-hydroxy-eicosatetraenoic acid (15S-HETE), an endogenous ligand for PPAR␥, was significantly decreased in the serum of patients with colorectal cancer. Treatment of colon cancer cells with 15S-HETE inhibited cell proliferation and induced apoptosis, which was preceded by an increase in TGF-␤-inducible early gene (TIEG) and a decrease in Bcl-2. The action of 15S-HETE could be blocked when PPAR␥ was suppressed. Overexpression of Bcl-2 prevented the apoptosis. The levels of TIEG and 15-lipoxygenase (15-LOX), the enzyme responsible for 15S-HETE production, was decreased in colorectal cancer. Therefore, colorectal cancer is associated with decreased 15S-HETE. Treatment of colon cancer cells with 15S-HETE inhibits cell proliferation and induces apoptosis in a PPAR␥-dependent pathway involving augmentation of TIEG and reduction of Bcl-2 expression.

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“…Should we measure endogenous prostglandins or in vitro synthesis of prostaglandins? Several different assay methods are available, including measurement of exogenous synthesis of PGs, as in ex vivo culture of colonic biopsies incubated with [ 14 C] arachidonic acid and measurement of radiolabelled products [43,44]; and measurement of endogenous synthesis of PGs, by snap-freezing freshly obtained minimally manipulated tissue, assaying it within an hour of procurement [42,45], and either adding indomethacin to the snap-frozen tissue [41] or homogenizing it at 0°C before incubation at high temperature to stop PG production [45]. Assay recovery may vary with extraction techniques (formic acid/radioimmunoassay method [41] vs. chloroform extraction and gas chromatographymass spectroscopy method [46]).…”

Section: Development Of Prostaglandins (Pgs) As Potential Sebs Of Drumentioning

confidence: 99%

Colon cancer chemoprevention: Clinical development of aspirin as a chemopreventive agent

Krishnan¹,

Brenner²

1997

J. Cell. Biochem.

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We have studied aspirin as a potential chemopreventive for colorectal cancer, completing Phase I studies on aspirin pharmacology and potential biomarker assays (prostaglandins, PGE 2 and PGF 2␣ and cyclooxygenase modulation) in normal human subjects. These studies have determined the optimal dose of aspirin for future Phase IIa and IIb chemopreventive trials in high-risk cohorts of patients for colon cancer. Aspirin's effects on rectal prostaglandins are prolonged, detectable even after aspirin and its metabolite are removed from the plasma. Aspirin-mediated inhibition of prostaglandin production in the human rectal epithelium may be related to direct suppression of cyclooxygenase transcription and not to enzyme inactivation by acetylation. A systematic method to monitor adherence (self-report, telephone contact, pill count, and microelectronic monitoring) has been established for future trials. Strategies to improve recruitment of high-risk cohorts have been developed. Phase IIa non-randomized studies with aspirin at 81 mg in high-risk cohorts (resected Duke's A colon cancer, Duke's C colon cancer treated with adjuvant therapy and disease-free at 5 years, history of colon adenomas Ͼ 1 cm, two or more first-degree relatives with colon cancer, and familial adenomatous polyposis and hereditary non-polyposis colorectal cancer syndromes) are currently being conducted for surrogate end-point biomarker (prostaglandins, cyclooxygenase, cellular mucins, and proliferation) modulation. J. Cell. Biochem. Suppls. 28/29:148-158. 1998 Wiley-Liss, Inc. †

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15-HETE is the main eicosanoid formed by human colonic mucosa

Cited by 12 publications

References 22 publications

Effect of Fish Oil on Levels ofR- andS-Enantiomers of 5-, 12-, and 15-Hydroxyeicosatetraenoic Acids in Mouse Colonic Mucosa

Effect of Fish Oil on Levels ofR- andS-Enantiomers of 5-, 12-, and 15-Hydroxyeicosatetraenoic Acids in Mouse Colonic Mucosa

15‐hydroxy‐eicosatetraenoic acid arrests growth of colorectal cancer cells via a peroxisome proliferator‐activated receptor gamma‐dependent pathway

Colon cancer chemoprevention: Clinical development of aspirin as a chemopreventive agent

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