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首页> 外文期刊>The Journal of Nutritional Biochemistry >Curcumin homing to the nucleolus: mechanism for initiation of an apoptotic program
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Curcumin homing to the nucleolus: mechanism for initiation of an apoptotic program

机译：姜黄素归巢到核仁：凋亡程序的启动机制。

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Curcumin is a plant-derived polyphenol that displays antitumor properties. Incubation of cultured SF-767 glioma cells with curcumin gave rise to intense intranuclear foci of curcumin fluorescence. In vitro studies revealed that nuclear homing by curcumin is not a result of DNA/chromatin binding. On the other hand, curcumin fluorescence colocalized with nucleophosmin, a nucleolus marker protein. To determine the temporal relationship between curcumin-induced apoptosis and nucleolar homing, confocal live cell imaging was performed. The data show that curcumin localization to the nucleolus occurs prior to cell surface exposure of phosphatidylserine. In studies of the mechanism of curcumin-induced apoptosis in SF-767 cells, its effect on the subcellular location of p14(ARF) was determined. Whereas p14(ARF) was confined to the nucleolus in untreated cells, 2 h following incubation with curcumin, it displayed a diffuse nuclear distribution. Given the role of nuclear p14(ARF) in binding the E3 ubiquitin ligase, mouse double minute 2 homolog (MDM2), the effect of curcumin treatment on cellular levels of the tumor suppressor protein, p53, was examined. Between 2 and 4 h following curcumin treatment, p53 levels increased with maximum levels reached by 8 h. Thus, curcumin homing to the nucleolus induces redistribution of p14(ARF) to the nucleoplasm where interaction with MDM2 leads to stabilization of p53, with subsequent initiation of apoptosis. (C) 2014 Elsevier Inc. All rights reserved.
机译：姜黄素是一种植物性多酚，具有抗肿瘤特性。将姜黄素与培养的SF-767胶质瘤细胞一起孵育会产生强烈的姜黄素荧光核内灶。体外研究表明姜黄素的核归巢不是DNA /染色质结合的结果。另一方面，姜黄素荧光与核糖蛋白（一种核仁标记蛋白）共定位。为了确定姜黄素诱导的凋亡与核仁归巢之间的时间关系，进行了共聚焦活细胞成像。数据显示姜黄素定位于核仁发生在磷脂酰丝氨酸的细胞表面暴露之前。在研究姜黄素诱导的SF-767细胞凋亡的机制中，确定了其对p14（ARF）亚细胞定位的影响。与姜黄素孵育2小时后，p14（ARF）被限制在未处理细胞的核仁中，它显示出弥散的核分布。鉴于核p14（ARF）在结合E3泛素2同源物小鼠双分钟2同源物（MDM2）中的作用，研究了姜黄素治疗对肿瘤抑制蛋白p53细胞水平的影响。姜黄素治疗后2至4小时内，p53水平升高，最大水平达到8 h。因此，姜黄素归巢到核仁会诱导p14（ARF）重新分布到核质，与MDM2的相互作用导致p53稳定，随后引发凋亡。 （C）2014 Elsevier Inc.保留所有权利。

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