Noscapine induced apoptosis via downregulation of survivin in human neuroblastoma cells having wild type or null p53.
Noscapine induced apoptosis via downregulation of survivin in human neuroblastoma cells having wild type or null p53.
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DOI：
10.1371/journal.pone.0040076
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Joshi HC
中科院分区：
文献类型：
--
作者：
Li S;He J;Li S;Cao G;Tang S;Tong Q;Joshi HC
神经母细胞瘤是儿童最常见的颅外实体瘤。它占儿童癌症死亡的 15%。化疗是晚期神经母细胞瘤儿童的主要治疗方法。那斯卡品是一种无毒的天然化合物，可以引发多种癌症类型的细胞凋亡。我们现在表明，p53 对于神经母细胞瘤细胞系中 Noscapine 诱导的细胞死亡是可有可无的，对这种有前途的化学预防剂的促凋亡反应是通过抑制生存素蛋白表达来介导的。 Noscapine 治疗增加了 SK-SY5Y 细胞中总 p53 蛋白和 Ser15 磷酸化 p53 蛋白的水平，但即使在 p53 蛋白水平被敲低后，对该药物的促凋亡反应仍得以维持。 SK-SY5Y 和 LA1-5S 细胞暴露于 Noscapine 后，早在治疗后 12 小时就导致生存素的蛋白质和 mRNA 水平显着下降。存活蛋白的异位表达对诺斯卡平介导的细胞质组蛋白相关的细胞凋亡 DNA 片段化具有统计学显着的保护作用。此外，在这两种细胞系中，生存素的 RNA 干扰会适度但统计学上显着地增强诺斯卡平诱导的细胞凋亡。此外，Noscapine 诱导的细胞凋亡与 caspase-3 的激活和 PARP 的裂解有关。总之，本研究为诺斯卡平诱导的细胞凋亡的分子回路提供了新的见解，表明抑制生存素表达是该过程的关键介质。
Neuroblastoma is the most common extracranial solid tumor of childhood. It accounts for 15% of pediatric cancer deaths. Chemotherapy is the mainstay of treatment in children with advanced neuroblastoma. Noscapine, a nontoxic natural compound, can trigger apoptosis in many cancer types. We now show that p53 is dispensable for Noscapine-induced cell death in neuroblastoma cell lines, proapoptotic response to this promising chemopreventive agent is mediated by suppression of survivin protein expression. The Noscapine treatment increased levels of total and Ser15-phosphorylated p53 protein in SK-SY5Y cells, but the proapoptotic response to this agent was maintained even after knockdown of the p53 protein level. Exposure of SK-SY5Y and LA1-5S cells to Noscapine resulted in a marked decrease in protein and mRNA level of survivin as early as 12 hours after treatment. Ectopic expression of survivin conferred statistically significant protection against Noscapine-mediated cytoplasmic histone-associated apoptotic DNA fragmentation. Also, the Noscapine-induced apoptosis was modestly but statistically significantly augmented by RNA interference of survivin in both cell lines. Furthermore, Noscapine-induced apoptotic cell death was associated with activation of caspase-3 and cleavage of PARP. In conclusion, the present study provides novel insight into the molecular circuitry of Noscapine-induced apoptosis to indicate suppression of survivin expression as a critical mediator of this process.
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影响因子：
50.3
作者：
Gu L;Zhu N;Zhang H;Durden DL;Feng Y;Zhou M
通讯作者：
Zhou M
影响因子：
5.8
作者：
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通讯作者：
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DOI：
10.2174/1568011023354452
发表时间：
2002-01-01
期刊：
Current Medicinal Chemistry - Anti-Cancer Agents
影响因子：
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作者：
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通讯作者：
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影响因子：
11.5
作者：
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通讯作者：
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影响因子：
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作者：
Mirza, A;McGuirk, M;Liu, SX
通讯作者：
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