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Inhibition of NF-kB in Prostate Cancer Cells by Vitamin E Succinate (VES) Supresses: Expression of IL-6, IL-8, VEGF, ICAM-1, Cell Invasiveness, and Cell Adhesion.
Paul L Crispen1, Richard E. Greenberg2, David Y. T. Chen2, Alan Pollack2, Eric M Horwitz2, Valdimir M Kolenko2, Robert G Uzzo2
1Temple University Hospital, Philadelphia, PA;2Fox Chase Cancer Center, Philadelphia, PA
Introduction:
The value of Vitamin E in the primary chemoprevention of prostate cancer is currently under investigation. However, the mechanism by which Vitamin E delays or prevents the progression of prostate cancer is not established. Aberrant transcriptional regulation of NK-kB dependent genes are believed to be a major event contributing to malignant transformation and progression of prostate cancer. We examine the ability of the alpha-tocopherol succinate (VES), a vitamin E analogue, to modulate activity of NF-kB in PC-3 and DU-145 human prostate cancer lines.
Methods:
PC-3 and DU-145 cells were cultured with and without varying concentrations of VES (10-30 ug/ml) followed by stimulation with TNF-alpha. Nuclear extracts were isolated and assayed for NF-kB activity by TransAmTM assay. IL-6,IL-8,and VEGF levels were assessed in the cellular supernatants by ELISA. ICAM-1 expression was assessed by flow cytometry. Cell invasiveness was examined by FluoroblokTM assay. Cell adhesion was examined by the ability of cells to adhere to fibronectin coated plates.
Results:
VES inhibits NF-kB activity in PC-3 and DU-145 cells. Treatment with VES reduced expression of IL-6, IL-8, VEGF and ICAM-1. We further demonstrate that VES suppresses tumor cell invasiveness and adhesion.
Conclusions:
Our findings suggest that vitamin E may prevent prostate carcinogenesis through suppression of NF-kB activity. Here we show that VES mediated inhibition of NF-kB activity coincides with suppression of NF-kB regulated molecules and decreased cell invasiveness and adhesion. Our data propose a potential mechanism and support the role of vitamin E as a chemopreventative agent against prostate cancer.
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