Roles of PI3-K/Akt pathways in nanoparticle realgar powders-induced apoptosis in U937 cells

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	Roles of PI3-K/Akt pathways in nanoparticle realgar powders-induced apoptosis in U937 cells
其他题名	Roles of PI3-K/Akt pathways in nanoparticle realgar powders-induced apoptosis in U937 cells
	Xi Ronggang 1; Huang Jian 1; Li Dan 1; Wang Xiaobo 1; Wu Lijun 1
	2008
发表期刊	ACTA PHARMACOLOGICA SINICA
ISSN	1671-4083
卷号	29 期号:3 页码:355-363
摘要	Aim: To study the mechanism by which nanoparticle realgar powders (NRP) induce human histocytic lymphoma U937 cell apoptosis. Methods: After the U937 cells were treated with various doses of NRP, the viability of the NRP-induced U937 cells was detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphen-yltetrazolium bromide (MTT) assay. Granular apoptotic bodies with membrane blebbing and condensed nuclei were observed by fluorescence microscopy. The apoptotic ratio induced by NRP was measured by lactate dehydrogenase (LDH) activity-based assay. Caspase-3 and the expressions of Akt, p-Akt, a nicotin-amide adenine dinucleotide (NAD(+))-dependent histone deacetylase (SIRT1), p53, and p-p53 were detected by Western blot analysis. Results: The growth-inhibitory activity of NRP for U937 cells was in a time-and dose-dependent manner. After treatment with various concentrations of NRP for 24 h, the majority of U937 cells underwent apoptosis as measured by LDH assay. In the presence of NRP, wortmannin, the inhibitor of phosphoinositide 3-kinase (PI3-K), and Akt inhibitor KP372-1 augmented the NRP-induced cell apoptosis. When the U937 cells were treated with NRP for the indicated time periods, procaspase-3 was gradually degraded and the activated caspase-3 was significantly increased. The expressions of anti-apoptotic proteins Akt and p-Akt were downregulated. Importantly, the inhibition of SIRT1 contributed to the activation of p53 and the inactivation of the PI3-K/Akt signaling pathway increased the expression of the p53 protein and downregulated the SIRT1 protein expression. Conclusion: The PI3-K/Akt signaling pathway plays an important role in NRP-induced U937 cell apoptosis. The reduced SIRT1 expression and activated p53 might be partially due to the inhibition of the PI3-K/Akt pathway triggered by the NRP-induced initiation of U937 cell apoptosis.
其他摘要	Aim: To study the mechanism by which nanoparticle realgar powders (NRP) induce human histocytic lymphoma U937 cell apoptosis. Methods: After the U937 cells were treated with various doses of NRP, the viability of the NRP-induced U937 cells was detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphen-yltetrazolium bromide (MTT) assay. Granular apoptotic bodies with membrane blebbing and condensed nuclei were observed by fluorescence microscopy. The apoptotic ratio induced by NRP was measured by lactate dehydrogenase (LDH) activity-based assay. Caspase-3 and the expressions of Akt, p-Akt, a nicotin-amide adenine dinucleotide (NAD+)-dependent histone deacetylase (SIRT1), p53, and p-p53 were detected by Western blot analysis. Results: The growth-inhibitory activity of NRP for U937 cells was in a time-and dose-dependent manner. After treatment with various concentrations of NRP for 24 h, the majority of U937 cells underwent apoptosis as measured by LDH assay. In the presence of NRP, wortmannin, the inhibitor of phosphoinositide 3-kinase (PI3-K), and Akt inhibitor KP372-1 augmented the NRP-induced cell apoptosis. When the U937 cells were treated with NRP for the indicated time periods, procaspase-3 was gradually degraded and the activated caspase-3 was significantly increased. The expressions of anti-apoptotic proteins Akt and p-Akt were downregulated. Importantly, the inhibition of SIRT1 contributed to the activation of p53 and the inactivation of the PI3-K/Akt signaling pathway increased the expression of the p53 protein and downregulated the SIRT1 protein expression. Conclusion: The PI3-K/Akt signaling pathway plays an important role in NRP-induced U937 cell apoptosis. The reduced SIRT1 expression and activated p53 might be partially due to the inhibition of the PI3-K/Akt pathway triggered by the NRP-induced initiation of U937 cell apoptosis.
关键词	SIGNAL-REGULATED KINASE A375-S2 CELLS CYTOCHROME-C HELA-CELLS P53 ACTIVATION CANCER MDM2 DEGRADATION INHIBITION nanoparticle realgar powders apoptosis caspase-3 phosphoinositide 3-kinase Akt a nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylase (SIRT1) p53
收录类别	CSCD
语种	英语
CSCD记录号	CSCD:3250442
引用统计	被引频次：4[CSCD] [CSCD记录]
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/154931
专题	中国科学院金属研究所
作者单位	1.中国科学院金属研究所 2.210th Hosp Peoples Liberat Army, Department Pharm, Dalitan 116000, Peoples R China 3.210th Hosp Peoples Liberat Army, Department Tradit Chinese Med, Dalitan 116000, Peoples R China Department Tradit Chinese Med
推荐引用方式 GB/T 7714	Xi Ronggang,Huang Jian,Li Dan,et al. Roles of PI3-K/Akt pathways in nanoparticle realgar powders-induced apoptosis in U937 cells[J]. ACTA PHARMACOLOGICA SINICA,2008,29(3):355-363.
APA	Xi Ronggang,Huang Jian,Li Dan,Wang Xiaobo,&Wu Lijun.(2008).Roles of PI3-K/Akt pathways in nanoparticle realgar powders-induced apoptosis in U937 cells.ACTA PHARMACOLOGICA SINICA,29(3),355-363.
MLA	Xi Ronggang,et al."Roles of PI3-K/Akt pathways in nanoparticle realgar powders-induced apoptosis in U937 cells".ACTA PHARMACOLOGICA SINICA 29.3(2008):355-363.