Curcurnin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21WAF1/CIP1 and C/EBPβ expressions and suppressing NF-κB activation
Curcurnin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21WAF1/CIP1 and C/EBPβ expressions and suppressing NF-κB activation
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DOI：
10.1002/pros.10089
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发表时间：
2002-05-15
期刊：
影响因子：
2.8
通讯作者：
Pu, YS
中科院分区：
文献类型：
--
作者：
Hour, TC;Chen, J;Pu, YS
背景探讨姜黄素（curcumin，CCM）对前列腺癌化疗药物细胞毒性的调节作用及其分子机制。通过三种不同的给药方案（一种同时治疗和两种顺序治疗）在两种雄激素非依赖性前列腺癌AIPC细胞（PC-3和DU 145）中检查CCM和化疗剂的联合作用。流式细胞术、Western blotting和凝胶迁移试验分别检测PC-3细胞周期进程、蛋白水平和转录激活的改变。CCM化疗药物方案的联合作用显示出最大的协同细胞毒性时，在两种细胞中的其他两个方案相比。CCM诱导PC-3细胞显著的G1期阻滞，这可能是通过诱导p21（WAF 1/CIP 1）和C/EBP β介导的。此外，CCM能够抑制宪法和TNF-α诱导的NF-κ B激活的时间依赖性方式。CCM与细胞毒疗法的结合可能是治疗AIPC的一个有前途的策略。(C)2002 Wiley-Liss，Inc.
BACKGROUND. The modulatory effects and molecular mechanisms of curcumin (CCM) on the cytotoxicity of chemotherapeutic agents to prostate cancer cells were explored.METHODS. The combined effects of CCM and chemotherapeutic agents were examined by three different administration schedules (one concurrent and two sequential treatments) in two androgen-independent prostate cancer AIPC) cells (PC-3 and DU145). Alteration of cell cycle progression, protein levels, and transcriptional activation in PC-3 cells were assayed by flow cytometry, Western blotting, and gel shift assay, respectively.RESULTS. The combined effects of CCM chemotherapeutic agent schedule showed the greatest synergistic cytotoxicity when compared to the other two schedules in both cells. CCM induced a significant G1 arrest in PC-3, which may be mediated by the induction of p2l (WAF1/CIP1) and C/EBPbeta. Moreover, CCM was able to inhibit both the constitutional and TNF-alpha-induced NF-kappaB activation in a time-dependent manner.CONCLUSIONS. The incorporation of CCM into cytotoxic therapies may be a promising strategy for the treatment of AIPC. (C) 2002 Wiley-Liss, Inc.