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101.
观察没食子酸丙酯(Propyl gallate,PG)对人慢性髓系白血病K562细胞株的增殖抑制及诱导凋亡作用.采用倒置显微镜观察细胞形态及数目的变化,乳酸脱氢酶(Lactate dehydrogenase,LDH)释放检测细胞活性,流式细胞术PI染色法及DNA倍体分析检测细胞凋亡作用.结果表明,没食子酸丙酯能有效地抑制K562细胞增殖,药物处理24 h时细胞形态发生变化,细胞数目减少;细胞培养液中LDH活性分析显示,20~300μg/mL没食子酸丙酯处理24 h对细胞毒性作用不明显;但处理时间达48 h时,没食子酸丙酯对细胞毒性明显增加;亚二倍体峰(凋亡峰)的出现及DNA片段化分析表明,200μg/mL PG处理细胞24 h时,能引起K562细胞凋亡.结果表明,PG具有明显的体外抗肿瘤活性,其抗癌活性与其抑制细胞增殖、诱导细胞凋亡有关.图5参18 相似文献
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A new series of 3-phenoxyazetidin-2-ones (β-lactams) were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In this study, the effects of a synthetic of β-lactam-structured COX-2 inhibitor with 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one on cell viability of cancerous lymphoblast isolated from patients diagnosed with acute lymphocytic leukemia (ALL) and normal lymphocytes collected from healthy donors were investigated. The viability % of cancer lymphoblast and normal lymphocyte treated 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one were tested with MTT assay. Apoptosis and necrosis were measured by double stains of annexin V and propidium iodide, and caspase-3 as a final mediator in apoptotic death measured by colorimetric assay. Mitochondria were isolated from both cancerous lymphoblast and normal lymphocytes to measure parameters of mitochondrial damage such as reactive oxygen species (ROS) formation, mitochondrial membrane potential decrease, swelling, and cytochrome c release following the administration of azithidine-2-one derivative, 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one. Our results showed that 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one inhibited proliferation of cancerous lymphoblast in a concentration-dependent manner by inducing apoptosis but not in normal lymphocytes. Treatment with azithidine-2-one derivative produced a rapid loss of mitochondrial transmembrane potential, stimulation of release of ROS and mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 processing. Data suggest that 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one-induced ROS production led to mitochondria-mediated death signaling that resulted in apoptosis in cancerous lymphoblast cells. The induction of apoptosis by azithidine-2-one compounds, such as 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one, may provide a mechanism for its cancer chemopreventive action in acute lymphocytic leukemia cells. 相似文献
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2,2’,4,4’-四溴联苯醚(BDE-47)是生物体中含量最高且毒性最强的PBDEs之一,有关BDE-47对肾细胞的毒性及其作用机制的研究仍有待补充。选取3个剂量组(低:10-6mol·L-1、中:10-5mol·L-1、高:10-4mol·L-1)及溶剂对照组,研究了BDE-47对人胚肾细胞(HEK293)的细胞凋亡率及活性氧(ROS)水平的影响;并从分子水平对细胞氧化损伤、凋亡相关蛋白(APE1及p53)及凋亡相关基因m RNA(p53、Bax、Caspase 3、Caspase 8)的表达量进行测定。实验结果显示:与对照组相比,中、高剂量组细胞凋亡率显著增加(P0.05);ROS水平在中剂量组显著上升(P0.01);随BDE-47浓度的变化,APE1蛋白表达量与细胞ROS水平存在一致性;p53、Bax、Caspase 8 m RNA表达量与BDE-47的浓度间存在剂量-效应关系。结果表明,BDE-47可诱导HEK293细胞凋亡及氧化应激,APE1可能是细胞ROS升高与细胞凋亡间重要的中介因子;BDE-47可以通过影响Caspase 8及线粒体途径中p53及Bax的表达诱导细胞凋亡。 相似文献
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三丁基锡对正常人胚胎羊膜细胞凋亡的诱导作用 总被引:4,自引:1,他引:3
为了探讨三丁基锡(TBT,tributyltin)对正常人羊膜细胞FL(humanamnioticcells)凋亡的诱导作用,进行了流式细胞仪PIAnnexinⅤ双染色检测TBT对FL细胞凋亡的诱导作用,并采用荧光染料FITC标记的特异性的caspase3的抑制剂检测活细胞中caspase3的酶活性.实验结果表明,0、1、2、3、4μmol·L-1浓度的三丁基锡作用于FL细胞2h后,细胞凋亡率和细胞中caspase3酶活性都明显升高,且有良好的剂量效应关系.表明三丁基锡在一定浓度和暴露时间下能够诱导FL细胞的凋亡,而且在此过程中,caspase3起重要作用. 相似文献
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The effects of deoxynivalenol in different dose including 100, 200, 500, 1000, and 1500 µg/L on primary cranial osteoblasts from fetal mice were investigated. Fluorescence staining, flow cytometric measurement, 3-(4,5-dimethylthiazol 2-y1)-3,5-di-phenyltetrazolium bromide assay, quantitative PCR, and Western blot were used for the test. Mineralization and proliferation of osteoblasts decreased upon 100 µg/L and higher deoxynivalenol treatment and apoptosis of osteoblasts was increased upon 500, 1000, and 1500 µg/L deoxynivalenol treatment. Karyopyknosis, membrane breakage, and a decreased number of calcium nodes were also observed upon 500 µg/L deoxynivalenol treatment. The mRNA and protein levels of B-cell lymphoma-2-associated X protein were upregulated, B-cell lymphoma-2 protein downregulated with increasing concentrations of deoxynivalenol treatment and their ratio increased. Deoxynivalenol induces apoptosis of osteoblasts, suggesting a mechanism by which deoxynivalenol can affect murine skeletal development. 相似文献
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Effect of titanium dioxide nanoparticles on the expression of apoptotic markers in mouse blastocysts
Oocyte maturation, embryo development and expression of apoptotic-specific genes were evaluated in blastocysts of mice treated with titanium dioxide nanoparticles. Female mice received 0, 50 or 100?mg/kg/day titanium dioxide intraperitoneally for five consecutive days. After the last injection, pregnant mare serum gonadotropin and, 48?h later, human chorionic gonadotropin were administered intraperitoneally for induction of ovulation. After 14?h, mice were sacrificed and oocytes were collected. The number of mature oocytes was evaluated and then fertilization was carried out in vitro and the numbers of fertilized and cleaved oocytes and of blastocysts and the expression of Bax, caspase 3, and Bcl-xL genes in blastocysts were evaluated. The number of mature, fertilized and cleaved oocytes and of blastocyst embryos in the experimental groups were not different from control. The expression of Bax and caspase 3 genes was significantly elevated in the experimental groups compared to control, while expression of the Bcl-xL gene was significantly lower in the high dose group. Uptake of titanium dioxide nanoparticles at daily doses of 50?mg/kg and more may affect embryo development by alteration of pro-apoptotic and anti-apoptotic gene expression. 相似文献
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五氯酚暴露诱导斑马鱼胚胎细胞凋亡相关基因的变化及caspase-2基因克隆和系统进化分析 总被引:3,自引:2,他引:1
应用基因芯片技术研究发现,暴露于五氯酚的斑马鱼胚胎中有14个涉及细胞凋亡行为的基因表达发生了显著改变.利用生物信息学方法构建这些功能基因系统进化树,分析与环境毒物诱导的细胞凋亡行为密切相关的caspase-2基因和其他基因之间的同源关系.斑马鱼caspase-2基因由10个外显子和9个内含子组成,cDNA长1308bp,含一个开放阅读框(ORF),编码435个氨基酸.6种脊椎动物Caspase-2氨基酸序列的保守性及系统进化分析结果表明,在特定功能区结构域中氨基酸序列表现出较高的同源性,Caspase-2在进化上高度保守.利用RT-PCR技术,斑马鱼caspase-2基因cDNA被克隆并确认.研究结果表明斑马鱼caspase-2基因是一个研究细胞凋亡行为的模型分子,可为环境化合物的分子毒性评价及其机制研究提供一种分子标记。 相似文献
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Elio Arias 《毒物与环境化学》2013,95(4):671-677
Phenoxyherbicides induce peroxisome proliferation, as do other structurally related or unrelated chemicals which were found to be nongenotoxic carcinogens in rodents. The widespread use of 2,4-dichlorophenoxyacetic acid (2,4-D) raised concerns over the potential to produce cancer, yet results from epidemiological and experimental studies do not provide definitive evidence that 2,4-D is carcinogenic. The objective of the present study was to verify whether 2,4-D might interfere with cell growth similar to other peroxisome proliferators using cultured avian hepatocytes. Primary hepatocyte cultures from 18-day-old chick embryos were exposed to 2,4-D for up to 72 h followed by an assessment of replicative DNA synthesis and apoptosis. Further, peroxisome proliferation was evaluated. Results showed that 2,4-D stimulated DNA synthesis and suppressed spontaneous apoptosis, while the effects on peroxisome proliferation were less evident. 相似文献
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