Activation of peroxisome proliferator-activated receptor (PPAR)-gamma by 15S-hydroxyeicosatrienoic acid parallels growth suppression of androgen-dependent prostatic adenocarcinoma cells

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 [H-3]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. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.