Anticancer effects of 3,3'-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells.
Anticancer effects of 3,3'-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells.
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DOI：
10.3892/ol.2012.1063
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发表时间：
2013-02
期刊：
影响因子：
2.9
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Xu Y;Zhang J;Shi W;Liu Y
3,3′-二吲哚基甲烷（DIM）在许多人类癌细胞中显示出抗肿瘤作用。然而，关于DIM对鼻咽癌（NPC）细胞影响的研究很少。在本研究中，我们检测了DIM对低分化鼻咽癌细胞系CNE-2的体外抗肿瘤活性。并对其潜在的分子机制进行了探讨。用不同浓度的DIM处理CNE-2细胞不同时间。检测细胞增殖和凋亡，并探讨其分子机制。结果表明，浓度为15-100 μM的DIM对CNE-2细胞增殖具有剂量依赖性和时间依赖性的抑制作用。流式细胞术分析显示DIM治疗后亚g1细胞出现高峰，细胞凋亡率升高。DIM可提高裂解的Bid和Bax水平，增强线粒体膜去极化，使细胞色素c、Smac和Omi外排到细胞质中。在DIM治疗后，caspase -3、-8、-9和cleaved poly （adp -核糖）聚合酶（PARP）水平呈剂量依赖性上调。DIM还能抑制i -κB -α的磷酸化，并在体外对CNE-2细胞中Bcl-2、XIAP和NF-κB表现出剂量依赖性的抑制作用。这些结果表明，DIM通过诱导细胞周期阻滞在G0/G1期来抑制细胞增殖，并通过调节线粒体依赖途径中的多个分子诱导CNE-2细胞凋亡。DIM可能是一种预防和治疗鼻咽癌的药物。
The antitumor effects of 3,3′-diindolylmethane (DIM) are exhibited in a number of human cancer cells. However, there have been few studies performed concerning the effect of DIM on nasopharyngeal cancer (NPC) cells. In the present study, we examined the in vitro antitumor activity of DIM on the poorly differentiated NPC cell line CNE-2. The potential molecular mechanisms of the activity were also explored. CNE-2 cells were treated with varying concentrations of DIM for different times. Cell proliferation and apoptosis were detected and the molecular mechanisms involved in these effects were characterized. The results demonstrated that DIM at concentrations of 15–100 μM caused dose- and time-dependent inhibition of CNE-2 cell proliferation. Flow cytometry analysis revealed a high sub-G1 cell peak following treatment with DIM, and the rate of apoptosis increased. DIM may elevate the levels of cleaved Bid and Bax and enhance mitochondrial membrane depolarization, allowing the efflux of cytochrome c, Smac and Omi into the cytosol. The levels of caspases-3, -8 and -9 and cleaved poly (ADP-ribose) polymerase (PARP) were upregulated following DIM treatment in a dose-dependent manner. DIM also inhibits the phosphorylation of IκB-α, and showed dose-dependent inhibition of Bcl-2, XIAP and NF-κB in CNE-2 cells in vitro. These results indicate that DIM inhibits cell proliferation by inducing cell cycle arrest at G0/G1 phase and induces the apoptosis of CNE-2 cells by regulating multiple molecules in a mitochondria-dependent pathway. DIM may be a preventive and therapeutic agent against NPC.
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DOI：
10.1016/j.bbrc.2005.12.059
发表时间：
2006-02-10
影响因子：
3.1
作者：
Garikapaty, VPS;Ashok, BT;Tiwari, RK
通讯作者：
Tiwari, RK
影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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