Gamma tocopherol upregulates the expression of 15-S-HETE and induces growth arrest through a PPAR gamma-dependent mechanism in PC-3 human prostate cancer cells.

Chronic inflammation and dietary fat consumption correlates with an increase in prostate cancer. Our previous studies in the colon have demonstrated that γ-tocopherol treatment could upregulate the expression of peroxisome proliferator-activated preceptors (PPAR) γ, a nuclear receptor involved in fatty acid metabolism as well modulation of cell proliferation and differentiation. In this study, we explored the possibility that γ-tocopherol could induce growth arrest in PC-3 prostate cancer cells through the regulation of fatty acid metabolism. Growth arrest (40%) and PPAR γ mRNA and protein upregulation was achieved with γ-tocopherol within 6 h. γ-Tocopherol-mediated growth arrest was demonstrated to be PPAR γ dependent using the agonist GW9662 and a PPAR γ dominant negative vector. γ-tocopherol was shown not to be a direct PPAR γ ligand, but rather 15-S-HETE (an endogenous PPAR γ ligand) was upregulated by γ-tocopherol treatment. 15-Lipoxygenase-2, a tumor suppressor and the enzyme that converts arachidon...