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• W1936767008 startingPage "826" @default.
• W1936767008 abstract "Evidence indicates that diets enriched in n-3 polyunsaturated fatty acids (n-3 PUFAs) reduce the risk of prostate cancer, but biochemical mechanisms are unclear. Syndecan-1 (SDC-1), a transmembrane heparan sulfate proteoglycan, supports the integrity of the epithelial compartment. In tumor cells of epithelial lineage, SDC-1 is generally downregulated. This may result in perturbation of homeostasis and lead to progression of malignancy. Our studies have shown that the n-3 PUFA species, docosahexaenoic acid (DHA), increases SDC-1 expression in prostate tissues of Pten knockout (PtenP-/-) mice/cells and human prostate cancer cells. We have now determined that DHA-mediated up-regulation of SDC-1 induces apoptosis. Bovine serum albumin-bound DHA and exogenous human recombinant SDC-1 ecotodomain were delivered to PC3 and LNCaP cells in the presence or absence of SDC-1 small interfering (si)RNA. In the presence of control siRNA, both DHA and SDC-1 ectodomain induced apoptosis, whereas SDC-1 silencing blocked DHA-induced but not SDC-1 ectodomain-induced apoptosis. Downstream effectors of SDC-1 signaling linked to n-3 PUFA-induced apoptosis involved the 3β-phosphoinositide-dependent kinase 1 (PDK1)/Akt/Bad integrating network. A diet enriched in n-3 PUFA decreased phosphorylation of PDK1, Akt (T308), and Bad in prostates of PtenP-/- mice. Similar results were observed in human prostate cancer cells in response to DHA and SDC-1 ectodomain. The effect of DHA on PDK1/Akt/Bad signaling was abrogated by SDC-1 siRNA. These findings define a mechanism by which SDC-1-dependent suppression of phosphorylation of PDK1/Akt/Bad mediates n-3 PUFA-induced apoptosis in prostate cancer." @default.
• W1936767008 created "2016-06-24" @default.
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• W1936767008 date "2010-10-01" @default.
• W1936767008 modified "2023-10-14" @default.
• W1936767008 title "Syndecan-1-Dependent Suppression of PDK1/Akt/Bad Signaling by Docosahexaenoic Acid Induces Apoptosis in Prostate Cancer" @default.
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• W1936767008 doi "https://doi.org/10.1593/neo.10586" @default.
• W1936767008 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2950332" @default.
• W1936767008 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20927321" @default.
• W1936767008 hasPublicationYear "2010" @default.
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