Dietary gamma-linolenic acid suppression of prostate cancer growth in the Lobund-Wistar rat model of prostatic adenocarcinoma

The development, growth, maintenance and function of the prostate in both normal and abnormal conditions depend on numerous lipophilic hormone signals that include the androgens (testosterone, T and dihydrotestosterone, DHT) and eicosanoids (metabolites of arachidonic acid, AA). Alterations in the balance of these lipid hormone signals are suggested to facilitate malignancies in this gland and that dietary manipulation may offer an alternative means of suppressing the progression to malignancies. Although the n-6 polyunsaturated fatty acid gamma-linolenic acid (GLA) found in plant sources and its 15-lipoxygenase metabolite, 15S-hydroxyeicosatrienoic acid (15S-HETrE), have been shown to modulate proliferation, the beneficial effects of GLA in prostatic carcinogenesis is unknown. Thus, benign hyperplastic (BHC) and malignant tumorigenic prostatic epithelial cells (MTC) were employed to establish whether the androgens and eicosanoids are altered in malignancies and whether GLA/15S-HETrE could reverse the alteration. Incubation of MTC with [3H]-T resulted in marked conversion to [3H]-DHT whereas the addition of either GLA or 15S-HETrE suppressed the conversion when compared to similar incubation with BHC. Incubation of BHC and MTC with AA in combination with or without T or DHT revealed marked generation of 5-lipoxygenase (5-LOX)-derived 5S-hydroxyeicosatrienoic acid (5S-HETE) and cyclooxygenase (COX)-derived prostaglandin E2 (PGE2) paralleled with the elevated expression of COX-2 in the MTC when compared to the BHC.; To determine whether the in vitro findings are relevant in an in vivo situation, autochthonous prostate adenocarcinomas induced in Lobund-Wistar (L-W) rats were used to test the hypothesis that supplementation of the diet with GLA will attenuate the prostatic adenocarcinoma progression. The findings revealed a decrease in tumor growth in the NMU/T/GLA group supplemented with GLA as determined by weight, DNA content and prostate specific antigen (tumor marker of prostate cancer) and histological differences between the experimental groups. Comparison of the animal groups showed a significant increase in 5S-HETE and PGE2 in the NMU/T group (experimental showing cancer development) as well as increased expression of COX-2. Taken together, the findings show dietary supplementation with GLA can reduce prostatic cancer development in L-W rats by suppressing the generation of 5S-HETE and PGE 2, warranting further explorations in humans.