gamma-linolenic-acid and 15-hydroxyeicosanoic-acid

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.

Topics: Adenocarcinoma; Animals; Arachidonic Acid; Cyclooxygenase 2; Dihydrotestosterone; Dinoprostone; Disease Models, Animal; Disease Progression; Eicosanoic Acids; gamma-Linolenic Acid; Humans; Isoenzymes; Male; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Prostatic Hyperplasia; Prostatic Neoplasms; Rats; Tumor Cells, Cultured

Although dietary gamma-linolenic acid (GLA) and its 15-lipoxygenase metabolite, 15S-hydroxyeicosatrienoic acid (15S-HETrE), have been reported to exert antiproliferative activities in other systems, their role in prostatic carcinogenesis is unknown. To evolve a possible mechanism for the suppressive effect on growth of prostatic cells, we incubated GLA and 15S-HETrE with androgen-dependent prostatic adenocarcinoma cells. 15S-HETrE but not GLA markedly inhibited [(3)H]thymidine uptake in parallel with the upregulation of peroxisome proliferator-activated receptor-gamma expression (a growth modulating nuclear receptor). The data, taken together, suggest that dietary GLA via its in vivo metabolite 15S-HETrE could serve as an endogenous adjunct to attenuate prostatic tumorigenesis.

Topics: Adenocarcinoma; Cell Division; Dihydrotestosterone; Eicosanoic Acids; Flow Cytometry; gamma-Linolenic Acid; Humans; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Receptors, Cytoplasmic and Nuclear; Transcription Factors