PGs and monohydroxy fatty acids (products of AA oxygenation), collectively known as "eicosanoids", are constitutive modulators in the prostate gland. 1 The precursor AA (20:4n-6) is converted to 2-series PGs via the COX pathway and to monohydroxy fatty acids and leukotrienes via the LOX pathway. These metabolites have been reported in other systems to modulate downstream physiologic and pathophysiologic responses such as growth and metastases. 2,3 In addition to eicosanoids, the androgens, specifically T (⌬ 4 -androstene-17-ol-3-one) and its reduced metabolite DHT (5␣-androstan-17-ol-3-one), are constitutive modulators in the prostate gland. 4 In hormone-responsive tissue such as the prostate, T is converted to the biologically active metabolite DHT by the enzyme 5␣-reductase, thus making this enzyme key to hormonal regulation of the prostate gland. 5-7 DHT in turn binds to a nuclear receptor, which regulates cellular growth and gene expression. 8 -10 Despite this latter function of DHT, the interactions and effects of androgens and AA metabolites on the pathophysiology of prostate cancer have remained obscure. However, one in vitro study using androgen-responsive prostate cancer cells suggested that a relationship exists between androgens and lipid metabolism.11 Because eicosanoids are important biologic modulators in the pathogenesis of cancer, we designed this study to test the hypothesis that T and its in vivo metabolite (DHT) alter the metabolism of AA in BHCs and tumorigenic prostatic MTCs in culture and that the alteration in eicosanoid production may contribute, at least in part, to tumorigenesis in prostate cells. Thus, using cells derived from the Lobund-Wistar rat model of autochthonous prostate adenocarcinoma, we tested in vitro whether or not preincubation of cells with GLA, a dietary constituent of borage oil, and its 15-LOX metabolite (15S-HETrE) would suppress the growth of androgen-responsive prostate cancer cells.
MATERIAL AND METHODS
Propagation of cellsWe used the established and well-characterized prostatic BHC line NRP-152 and the malignant tumorigenic line NRP-154, which were generously provided by Dr. D. Danielpour (Ireland Cancer Center, Case Western Reserve University, Cleveland, OH). These cells were propagated as previously reported. 12 Briefly, both NRP-152 (derived from the prostate of Lobund-Wistar rats that had been previously treated only with N-nitroso-N-methylurea) and NRP-154 (derived from the prostate of Lobund-Wistar rats previously treated with N-nitroso-N-methylurea plus T) cells were maintained in GM2 [HEPES-free and antibiotic-free DMEM/F-12 (1:1, v/v) supplemented with 5% FBS, 20 ng/ml EGF, 10 ng/ml cholera toxin, 0.1 M dexamethasone and 5 g/ml insulin] in 80 cm 2