Suppression of cyclooxygenase-2 overexpression by 15S-hydroxyeicosatrienoic acid in androgen-dependent prostatic adenocarcinoma cells.
Emerging reports now implicate alterations of arachidonic acid (AA) metabolism with prostate carcinogenesis. To test this hypothesis, androgen-primed benign hyperplastic (BHC) and malignant tumorigenic (MTC) cells derived from the Lobund-Wistar rat model of autochthonous prostate adenocarcinoma were incubated with (14)C-AA. Our data using MTCs revealed enhanced dual metabolism of (14)C-AA via COX to generate increased PGE(2) and via 5-lipoxygenase (LOX) to generate increased 5S-HETE in tumorigenic cells. Western blot of MTCs revealed upregulation of COX-2 expression. This paralleled the increased biosynthesis of PGE(2). Since some polyunsaturated fatty acids have been reported to modulate AA metabolism and tumorigenesis, we primed the cells with either gamma-linolenic acid (GLA) or its in vivo metabolite, 15S-HETrE, prior to incubation with AA. Our data revealed suppression of COX-2 expression/PGE(2) biosynthesis. In parallel, priming cells with 15S-HETrE resulted in greater suppression of COX-2 expression/PGE(2) biosynthesis. These findings suggest that 15S-HETrE could function in vivo after dietary intake of GLA to suppress DHT-enhanced prostatic COX-2 expression/PGE(2) biosynthesis and, thus, alleviate tumor growth and progression.
Pham
Hung
H
Department of Dermatology, School of Medicine, University of California-Davis, 95616, USA.
Banerjee
Tinku
T
Ziboh
Vincent A
VA
D000230:Adenocarcinoma / Q000503:physiopathology*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D051546:Cyclooxygenase 2; D013196:Dihydrotestosterone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004195:Disease Models, Animal; D018450:Disease Progression; D004537:Eicosanoic Acids / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011470:Prostatic Hyperplasia / Q000503:physiopathology*; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D051381:Rats; D014407:Tumor Cells, Cultured; D017965:gamma-Linolenic Acid / Q000378:metabolism
D004537:Eicosanoic Acids; D007527:Isoenzymes; D008565:Membrane Proteins; D013196:Dihydrotestosterone; D016718:Arachidonic Acid; C073049:15-hydroxyeicosanoic acid; D017965:gamma-Linolenic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone