Vitamin E succinate induces apoptosis in human prostate cancer cells: Rolefor Fas in vitamin E succinate-triggered apoptosis

The apoptosis-triggering properties of vitamin E succinate (VES, RRR-alpha- tocopheryl succinate) for human LNCaP and PC-3 prostate carcinoma cells and normal PrEC human prostate epithelial cells were investigated LNCaP and PC -3 cells were sensitive to VES-induced apoptosis, with 100% and 60% of cell s undergoing apoptosis after three days of treatment with 10 mu g of VES/ml , respectively. PrEC cells were resistant to VES-induced apoptosis. Treatme nt of prostate cells with agonistic anti-Fas antibody triggered apoptosis i n approximately 50% of PC-S cells within 48 hours, whereas LNCaP and PrEC c ells were resistant. Prostate cells simultaneously treated with VES and ago nistic anti-Pas antibodies revealed 1) no effect on PrEC cells, 2) an addit ive effect on Fas-sensitive PC-3 cells, and 3) a synergistic effect on LNCa P cells. VES treatment of LNCaP cells caused depletion of cytosolic 43-kDa Fas, enhanced membrane levels of 43-kDa Fas, and induced Pas sensitivity. P C-3 cells expressed high levels of membrane 43-kDa Fas that were enhanced b y VES treatments. Fas ligand expression by LNCaP cells was enhanced by VES treatments. in summary, VES triggers apoptosis in human prostate carcinoma cells bur not normal prostate cells in vitro, and VES modulates Fas signali ng.