In Vivo and in Vitro Regulation of Syndecan 1 in Prostate Cells by n-3 Polyunsaturated Fatty Acids

Abstract

Syndecan 1 is the major proteoglycan produced by epithelial cells. It is strategically localized at the plasma membrane to participate in growth factor signaling and cell-cell and cell-matrix interactions. Its expression may modulate the properties of epithelial lineage tumor cells in which it is generally down-regulated compared with nontumor progenitors. The present study examined the regulation of syndecan 1 in prostate epithelial cells by n-3 polyunsaturated fatty acids. In prostate tissue of mice, syndecan 1 immunostaining was demonstrated in epithelial cells throughout each gland. In animals fed an n-3 polyunsaturated fatty acid-enriched diet, syndecan 1 mRNA was increased in all prostate glands. In the human prostate cancer cell line, PC-3, delivery of exogenous n-3 (but not n-6) fatty acids resulted in up-regulation of syndecan 1 expression. This effect was mimicked by a peroxisome proliferator-activated receptor (PPAR) ␥ agonist, troglitazone, and inhibited in the presence of a PPAR␥ antagonist and in cells transfected with dominant negative PPAR␥ cDNA. Using a luciferase gene driven either by a PPAR response element or by a DR-1 site present in the syndecan 1 promoter, reporter activation was increased by n-3 low density lipoprotein, docosahexaenoic acid, and troglitazone, whereas activity of a luciferase gene placed downstream of a mutant DR-1 site was unresponsive. These findings indicate that syndecan 1 is up-regulated by n-3 fatty acids by a transcriptional pathway involving PPAR␥. This mechanism may contribute to the chemopreventive properties of n-3 fatty acids in prostate cancer.

Dietary polyunsaturated fatty acids as inducers of apoptosis: implications for cancer

“…Factors involved in cellular uptake and incorporation of EPA into lipids of leukemia cells have been considered essential for its apoptosis-inducing effect [142][143][144][145]. Moreover, to explain the pro-apoptotic effect of DHA in different lung, pancreatic and prostate cancer cell lines [12,145,146] the modification in the activity and expression of different intracellular signaling molecules have been invoked. DHA can promote apoptosis: (1) in lung cancer cells through the up-regulation of MKP-1 phosphatase and down-regulation of p-ERK1/2 and p-p38 expression [12], (2) in prostate cancer cells through the activation of PPARc and up-regulation of SDC-1 [146], and (3) in human pancreatic cancer cells through the induction of an active extrusion process of GSH leading to its intracellular depletion and oxidative stress [145].…”

n-3 Polyunsaturated Fatty Acids and Their Role in Cancer Chemoprevention

“…Our own studies have found that in contrast to normal prostate epithelial cells and androgen independent PC3 and DU145 cells, SDC-1 protein expression was down-regulated in prostate cancer cell lines and androgen-dependent LNCaP cells [75]. In a Pten-null mouse prostate cancer model, we have also found that inhibition of prostate cancer growth by dietary n-3 PUFAs was associated with an increased expression of SDC-1 protein [75,76]. …”

Involvement of apoptotic pathways in docosahexaenoic acid-induced benefit in prostate cancer: Pathway-focused gene expression analysis using RT2 Profile PCR Array System

“…The increased apoptosis was observed following the treatment with a fish oil diet or DHA, with the possible induction of both the intrinsic and extrinsic apoptotic pathways [19]. The pro-apoptotic effect of DHA has been reported to involve modifications of the expression and activity of different intracellular apoptotic pathways [20, 21]. Therefore, to better understand the potential apoptotic pathways involved in DHA-induced apoptosis of prostate cancer cells, pathway-focused gene expression analysis was performed in our study using RT 2 Profile PCR Arrays.…”