Curcumin regulates low-linear energy transfer γ-radiation-induced NFκB-dependent telomerase activity in human neuroblastoma cells.
Curcumin regulates low-linear energy transfer γ-radiation-induced NFκB-dependent telomerase activity in human neuroblastoma cells.
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DOI：
10.1016/j.ijrobp.2010.10.058
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发表时间：
2011-03-15
影响因子：
7
通讯作者：
Natarajan, Mohan
中科院分区：
文献类型：
--
作者：
Aravindan, Natarajan;Veeraraghavan, Jamunarani;Madhusoodhanan, Rakhesh;Herman, Terence S.;Natarajan, Mohan
我们最近报道了姜黄素减弱辐射（IR）诱导的人神经母细胞瘤（NB）细胞的存活信号和增殖。在内皮细胞系统中，NFκB B也参与了IR诱导的端粒酶活性（TA）的调节。因此，我们研究了姜黄素在抑制IR诱导的NFκB依赖性hTERT转录、TA和NB细胞存活中的作用。在1小时至24小时后收获暴露于IR、用姜黄素（10 nM-100 nM）处理（有或没有IR）的SK-N-MC或SH-SY 5 Y细胞。使用pNFκB-、pGL 3 -354-、pGL 3 -347-、pUSE-IκBα-Luc、p50/p65或RelA siRNA转染的细胞，通过荧光素酶报告基因测定研究NFκB依赖性调节。采用EMSA分析NFκB活性，采用QPCR分析hTERT表达。用TRAP法测定TA，用MTT法和克隆形成法测定细胞存活率。姜黄素显著抑制IR诱导的NFκB。因此，姜黄素显着抑制IR诱导的TA和hTERTmRNA在所有时间点的研究。此外，IR诱导的TA在转录水平上通过触发TERT启动子激活来调节。此外，NFκB在IR后功能性活化，并通过与TERT基因启动子区的κ B结合区结合介导TA上调。因此，IκBα突变体消除端粒酶启动子上的NFκ B识别位点或抑制NFκB α表达，可抑制IR诱导的端粒酶启动子激活。姜黄素显著抑制IR诱导的TERT转录。姜黄素抑制NFκB过表达细胞中hTERT mRNA和TA的表达。此外，姜黄素增强IR诱导的细胞存活抑制。这些结果有力地表明，姜黄素抑制IR诱导的TA在人NB细胞中的NFκB依赖的方式。
We recently reported that curcumin attenuates radiation (IR) induced survival signaling and proliferation in human neuroblastoma (NB) cells. Also, in endothelial system, we demonstrated that NFκB regulates IR-induced telomerase activity (TA). Accordingly, we investigated the effect of curcumin in inhibiting IR-induced NFκB dependent hTERT transcription, TA and cell survival in NB cells. SK-N-MC or SH-SY5Y cells exposed to IR, treated with curcumin (10nM–100nM) with or without IR were harvested after 1h through 24h. NFκB dependent regulation was investigated either by luciferase reporter assays using pNFκB-, pGL3-354-, pGL3-347-, pUSE-IκBα-Luc, p50/p65 or RelA siRNA transfected cells. NFκB activity was analyzed using EMSA and hTERT expression using QPCR. TA was determined using TRAP assay and, cell survival using MTT and clonogenic assay. Curcumin profoundly inhibited IR-induced NFκB. Consequently, curcumin significantly inhibited IR-induced TA and hTERT mRNA at all time points investigated. Furthermore, IR-induced TA is regulated at the transcriptional level by triggering TERT promoter activation. Moreover, NFκB becomes functionally activated after IR and mediates TA upregulation by binding to the κB-binding region in the promoter region of the TERT gene. Consistently, elimination of NFκB-recognition site on telomerase promoter or inhibition of NFκB by IκBα mutant compromises IR-induced telomerase promoter activation. Significantly, curcumin inhibited IR-induced TERT transcription. Consequently, Curcumin inhibited hTERT mRNA and TA in NFκB overexpressed cells. Furthermore, curcumin enhanced the IR-induced inhibition of cell survival. These results strongly suggest that curcumin inhibits IR-induced TA in an NFκB dependent manner in human NB cells.
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影响因子：
56.9
作者：
FENG, JL;FUNK, WD;VILLEPONTEAU, B
通讯作者：
VILLEPONTEAU, B
影响因子：
2
作者：
Madhusoodhanan, Rakhesh;Natarajan, Mohan;Aravindan, Natarajan
通讯作者：
Aravindan, Natarajan
影响因子：
4
作者：
Aravindan, Natarajan;Mohan, Sumathy;Natarajan, Mohan
通讯作者：
Natarajan, Mohan
影响因子：
11.5
作者：
Kunnumakkara, Ajaikumar B.;Diagaradjane, Parmeswaran;Krishnan, Sunil
通讯作者：
Krishnan, Sunil
影响因子：
45.3
作者：
BERNSTEIN, ML;LECLERC, JM;WOODS, WG
通讯作者：
WOODS, WG