Gene expression profiling for nitric oxide prodrug JS-K to kill HL-60 myeloid leukemia cells.
Gene expression profiling for nitric oxide prodrug JS-K to kill HL-60 myeloid leukemia cells.
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DOI：
10.1016/j.ygeno.2009.03.005
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发表时间：
2009-07
期刊：
影响因子：
4.4
通讯作者：
Shami PJ
中科院分区：
文献类型：
--
作者：
Liu J;Malavya S;Wang X;Saavedra JE;Keefer LK;Tokar E;Qu W;Waalkes MP;Shami PJ
一氧化氮(NO)前体药物JS-K被证明具有抗癌活性。为了揭示JS-K抗癌作用相关的分子事件，我们用JS-K处理HL-60白血病细胞，并进行了基因芯片和实时荧光定量RT-PCR分析。JS-K可诱导HL-60细胞表达浓度和时间依赖的基因表达变化，与细胞毒性效应相对应。诱导凋亡基因(caspase、bax、肿瘤坏死因子-α)和分化相关基因(CD14、CD11b、Vimentin)表达增加。对于急性期蛋白基因，有些表达上调(p53、c-jun)，而另一些表达下调(c-myc、Cyclin E)。JS-K还上调了抗血管生成基因血栓反应蛋白-1和CD36以及参与肿瘤细胞迁移的金属蛋白酶组织抑制物等基因的表达。共聚焦分析证实了关键基因在蛋白质水平上的变化。因此，多个分子事件与JS-K对HL-60的杀伤作用有关，这可能是这种新型抗癌NO前体药物的分子靶点。
The nitric oxide (NO) prodrug JS-K is shown to have anticancer activity. To profile the molecular events associated with anticancer effects of JS-K, HL-60 leukemia cells were treated with JS-K and subjected to microarray and real-time RT-PCR analysis. JS-K induced concentration- and time-dependent gene expression changes in HL-60 cells corresponding to the cytolethality effects. The apoptotic genes (caspases, Bax, and TNF-α) were induced, and differentiation-related genes (CD14, CD11b, and vimentin) were increased. For acute phase protein genes, some were increased (p53, c-jun) while others were suppressed (c-myc, cyclin E). The expression of anti-angiogenesis genes thrombospondin-1 and CD36 and genes involved in tumor cell migration such as tissue inhibitors of metalloproteinases, were also increased by JS-K. Confocal analysis confirmed key gene changes at the protein levels. Thus, multiple molecular events are associated with JS-K effects in killing HL-60, which could be molecular targets for this novel anticancer NO prodrug.
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影响因子：
2.7
作者：
Cheng, Yun-Chih;Lin, Hsiupen;Liu, H. Eugene
通讯作者：
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影响因子：
3.8
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影响因子：
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作者：
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