Measurement of arachidonate and its metabolites extracted from human normal and malignant gastrointestinal tissues.

Abstract

SUMMARY This is the first report of human gastrointestinal arachidonate and prostanoids measured quantitatively by gas chromatography-mass spectrometry (GC-MS) The methods for gas chromatography-mass spectrometry (GC-MS) were as reported previously.' In brief, the dried extract obtained as described above was dissolved in dichloromethane. An aliquot was taken for GC-MS and further purified by LH20 column chromatography; non-polar impurities were eluted with dichloromethane, and the eicosanoids were eluted with methanol which was then evaporated. Deuterated standards were added, and each dried methanol extract was dissolved in doubledistilled water acidified to pH 3 with hydrochloric acid. Each solution was percolated through an Amberlite column which was then washed with distilled water, and the eicosanoids were eluted with 315 on 11 May 2018 by guest. Protected by copyright.

Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane‐induced colon carcinogenesis in male F344 rats

“…It is metabolized both by the COX pathway, which produces PGs, thromboxane and prostacyclin, and by the LOX pathway, which leads to the formation of leukotrienes and lipoxins. Arachidonic acid products synthesized via both pathways could modulate colon carcinogenesis, 45 and some inhibitors, 46 including LOX inhibitors of the arachidonic acid cascade, possess chemopreventive activity in colon carcinogenesis. 47 In this context, the inhibition of PG biosynthesis, 7 LOX 6 and COX-2 48 after silymarin dosing is of interest and important when considering possible mechanisms behind the chemopreventive effect of silymarin found in the present study.…”

Tumor suppressor p53 inhibits transcriptional activation of invasion gene thromboxane synthase mediated by the proto-oncogenic factor ets-1

“…Deregulation of the prostanoid synthesis plays an important role in pathogenesis and cancer progression (Surette et al, 1999). Prostanoid synthesis in neoplasms of breast, lung, colon, and also in neuroepithelial tumors of the central nervous system exceeds the levels of normal tissues (Bennett et al, 1977(Bennett et al, , 1987Castelli et al, 1989). The initial step in the biochemical pathway of prostanoid synthesis is the release of arachidonic acid from cellular membranes mediated by phospholipase A 2 .…”

Dihydroxy Bile Acids Activate the Transcription of Cyclooxygenase-2

“…Overexpression of COX-2 inhibits apoptosis and increases the invasiveness of malignant cells (15,16). Amounts of COX-2 are increased in transformed cells and tumors (7,(17)(18)(19), which results in enhanced synthesis of prostaglandins in malignant tissue (20,21). Given these data, a reasonable strategy for inhibiting carcinogenesis is to suppress the expression of COX-2 (22,23).…”