Phenethyl isothiocyanate-induced apoptosis in PC-3 human prostate cancer cells is mediated by reactive oxygen species-dependent disruption of the mitochondrial membrane potential
Phenethyl isothiocyanate-induced apoptosis in PC-3 human prostate cancer cells is mediated by reactive oxygen species-dependent disruption of the mitochondrial membrane potential
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DOI：
10.1093/carcin/bgl087
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发表时间：
2006-11-01
期刊：
影响因子：
4.7
通讯作者：
Singh, Shivendra V.
中科院分区：
文献类型：
--
作者：
Xiao, Dong;Lew, Karen L.;Singh, Shivendra V.
本研究以 PC-3 人前列腺癌细胞为模型，深入了解异硫氰酸苯乙酯 (PEITC) 诱导细胞凋亡的分子机制，PEITC 是十字花科蔬菜的癌症化学预防成分。 PEITC 诱导的 PC-3 细胞死亡与线粒体膜电位破坏、凋亡分子（细胞色素 c 和 Smac/DIABLO）从线粒体释放到细胞质以及活性氧 (ROS) 的产生有关，而这些分子在超氧化物歧化酶和过氧化氢酶 (Euk134) 组合模拟物的存在下被阻断。 Bcl-xL 的异位表达（其蛋白水平在用 PEITC 处理 PC-3 细胞时显着降低）仅在较高药物浓度（> 10 muM）下才对 PEITC 诱导的细胞凋亡提供部分保护。通过口服管饲方式每天（周一至周五）施用 12 μmol PEITC，可显着延缓无胸腺小鼠中 PC-3 异种移植物的生长。例如，开始给予 PEITC 后 31 天，对照小鼠的平均肿瘤体积 (721 +/- 153 mm(3)) 与每天接受 12 μmol PEITC 的小鼠相比，高出 2 倍。 PEITC 介导的 PC-3 异种移植物生长抑制与 Bax 和 Bid 蛋白的诱导有关。总之，本研究表明 PEITC 诱导的 PC-3 细胞凋亡是由 ROS 依赖性线粒体膜电位破坏介导的，并受 Bax 和 Bid 调节。
The present study was undertaken to gain insights into the molecular mechanism of apoptosis induction by phenethyl isothiocyanate (PEITC), which is a cancer chemopreventive constituent of cruciferous vegetables, using PC-3 human prostate cancer cells as a model. The PEITC-induced cell death in PC-3 cells was associated with disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria to the cytosol and generation of reactive oxygen species (ROS), which were blocked in the presence of a combined mimetic of superoxide dismutase and catalase (Euk134). Ectopic expression of Bcl-xL, whose protein level is reduced markedly on treatment of PC-3 cells with PEITC, conferred partial protection against PEITC-induced apoptosis only at higher drug concentrations (> 10 mu M). Administration of 12 mu mol PEITC/day (Monday through Friday) by oral gavage significantly retarded growth of PC-3 xenografts in athymic mice. For instance, 31 days after the initiation of PEITC administration, the average tumor volume in control mice (721 +/- 153 mm(3)) was similar to 2-fold higher compared with mice receiving 12 mu mol PEITC/day. The PEITC-mediated inhibition of PC-3 xenograft growth was associated with induction of Bax and Bid proteins. In conclusion, the present study indicates that the PEITC-induced apoptosis in PC-3 cells is mediated by ROS-dependent disruption of the mitochondrial membrane potential and regulated by Bax and Bid.