Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells

Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells
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DOI:
10.3748/wjg.v12.i35.5628
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发表时间:
2006-09-21
影响因子:
4.3
通讯作者:
Holian, Oksana
Holian, Oksana
中科院分区:
医学2区
文献类型:
--
作者:
Riles, William L.;Erickson, Jason;Holian, Oksana

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目的:研究白藜芦醇对三种胃腺癌细胞系细胞内凋亡信号的影响,方法:用核碎裂法定量凋亡细胞,用分光光度法检测caspase活性,用流式细胞仪检测细胞凋亡率,用流式细胞仪检测细胞凋亡率。氧化细胞色素C的形成用于测定细胞色素C活性,蛋白质印迹分析用于测定蛋白质表达。胃癌细胞,无论其p53状态如何,对白藜芦醇的反应是DNA片段化和核纤层蛋白A和B以及PARR的裂解。对线粒体相关凋亡蛋白Bcl-2、Bcl-A、Bax、Bid或Smac/Diablo没有影响,并且不促进细胞色素C的亚细胞再分布,表明白藜芦醇诱导的胃癌细胞凋亡不需要破坏线粒体膜完整性白藜芦醇上调SNU中p53蛋白,1和AGS细胞的凋亡信号,但这些细胞系之间的细胞内凋亡信号的反应存在差异。SNU-1细胞响应白藜芦醇治疗与下调生存素,而在AGS和KATO-III细胞白藜芦醇刺激caspase 3和细胞色素C氧化酶activity.CONCLUSION:这些研究结果表明,即使在一个特定的癌症细胞内的细胞凋亡信号从事白藜芦醇是细胞类型依赖性的,并建议这种差异可能与分化或缺乏这些细胞的分化。(C)2006年,WJG出版社。All rights reserved.
AIM: To investigate the intracellular apoptotic signals engaged by resveratrol in three gastric adenocarcinoma cancer cell lines, two of which (AGS and SNU-1) express p53 and one (KATO-M) with deleted p53.METHODS: Nuclear fragmentation was used to quantitate apoptotic cells; caspase activity was determined by photometric detection of cleaved substrates; formation of oxidized cytochrome C was used to measure cytochrome C activity, and Western blot analysis was used to determine protein expression.RESULTS: Gastric cancer cells, irrespective of their p53 status, responded to resveratrol with fragmentation of DNA and cleavage of nuclear lamins A and B and PARR Resveratrol, however, has no effect on mitochondria -associated apoptotic proteins Bcl-2, Bcl-A, Bax, Bid or Smac/Diablo, and did not promote subcellular redistribution of cytochrome C, indicating that resveratrol-induced apoptosis of gastric carcinoma cells does not require breakdown of mitochondrial membrane integrity Resveratrol up-regulated p53 protein in SNU-1 and AGS cells but there was a difference in response of intracellular apoptotic signals between these cell lines. SNU-1 cells responded to resveratrol treatment with down-regulation of survivin, whereas in AGS and KATO-III cells resveratrol stimulated caspase 3 and cytochrome C oxidase activities.CONCLUSION: These findings indicate that even within a specific cancer the intracellular apoptotic signals engaged by resveratrol are cell type dependent and suggest that such differences may be related to differentiation or lack of differentiation of these cells. (C) 2006 The WJG Press. All rights reserved.