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

Vitamin E succinate induces apoptosis in human prostate cancer cells: Role for Fas in vitamin E succinate-triggered apoptosis
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DOI:
10.1207/s15327914nc3601_13
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发表时间:
2000-01-01
影响因子:
2.9
通讯作者:
Kline, K
Kline, K
中科院分区:
医学4区
文献类型:
--
作者:
Israel, K;Yu, WP;Kline, K

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研究了维生素E琥珀酸酯(VES,RRR-alpha-生育酚琥珀酸酯)对人LNCaP和PC-3前列腺癌细胞以及正常PrEC人前列腺上皮细胞的凋亡触发特性。LNCaP和PC-3细胞对VES诱导的凋亡敏感,用10 μ g/ml VES处理3天后,分别有100%和60%的细胞发生凋亡。PrEC细胞对VES诱导的凋亡具有抗性。用激动性抗Fas抗体处理前列腺细胞在48小时内触发了约50%的PC-S细胞的凋亡,而LNCaP和PrEC细胞具有抗性。同时用VES和激动性抗Pas抗体处理的前列腺细胞显示:1)对PrEC细胞没有影响,2)对Fas敏感性PC-3细胞的累加效应,和3)对LNCaP细胞的协同效应。VES处理LNCaP细胞引起胞浆43-kDa Fas的耗竭,增强43-kDa Fas的膜水平,并诱导Pas敏感性。PC-3细胞表达高水平的膜43-kDa Fas,增强VES治疗。Fas配体的表达LNCaP细胞增强VES处理。总之,在体外,VES在人前列腺癌细胞中触发凋亡而不是在正常前列腺细胞中触发凋亡,并且VES调节Fas信号传导。
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 cells undergoing apoptosis after three days of treatment with 10 mu g of VES/ml, respectively. PrEC cells were resistant to VES-induced apoptosis. Treatment of prostate cells with agonistic anti-Fas antibody triggered apoptosis in approximately 50% of PC-S cells within 48 hours, whereas LNCaP and PrEC cells were resistant. Prostate cells simultaneously treated with VES and agonistic anti-Pas antibodies revealed 1) no effect on PrEC cells, 2) an additive effect on Fas-sensitive PC-3 cells, and 3) a synergistic effect on LNCaP cells. VES treatment of LNCaP cells caused depletion of cytosolic 43-kDa Fas, enhanced membrane levels of 43-kDa Fas, and induced Pas sensitivity. PC-3 cells expressed high levels of membrane 43-kDa Fas that were enhanced by 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 signaling.