Roles of PI3-K/Akt pathways in nanoparticle realgar powders-induced apoptosis in U937 cells
查看参考文献40篇
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文摘
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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. |
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来源
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Acta Pharmacologica Sinica
,2008,29(3):355-363 【核心库】
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DOI
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10.1111/j.1745-7254.2008.00759.x
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关键词
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nanoparticle realgar powders
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apoptosis
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caspase-3
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phosphoinositide 3-kinase
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Akt
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a nicotinamide adenine
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地址
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School of Traditional Chinese Medicines, Shenyang Pharmaceutical University, Shenyang, 110016
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语种
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英文 |
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文献类型
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研究性论文 |
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ISSN
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1671-4083 |
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学科
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药学 |
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文献收藏号
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CSCD:3250442
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参考文献 共
40
共2页
|
|
1.
Luo LY. Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by arsenic sulphide:Involvement of serine/threonine protein phosphatases.
Leuk Res,2006,30:1399-1405
|
被引
4
次
|
|
|
|
|
2.
Wu JZ. Evaluation of the in vitro activity and in vivo bio-availability of realgar nanoparticles prepared by cryo-grinding.
Eur J Pharm Sci,2006,29:35-44
|
被引
5
次
|
|
|
|
|
3.
Ning N. Realgar nano-particles induce apoptosis and necrosis in leukemia cell lines K562 and HL-60.
China J Chin Mat Med,2005,30:136-140
|
被引
3
次
|
|
|
|
|
4.
Kim SO. Pan-caspase inhibitor zVAD enhances cell death in RAW 246. 7 macrophages.
J Endotoxin Res,2001,7:292-296
|
被引
2
次
|
|
|
|
|
5.
Kawazoe N. Tiamil is involved in the regulation of bufalin-induced apoptosis in human leukemia cells.
Oncogene,1999,18:2413-2421
|
被引
12
次
|
|
|
|
|
6.
Hill PA. Multiple extracellular signals promote osteoblast survival and apoptosis.
Endocrinology,1997,138:3849-3858
|
被引
20
次
|
|
|
|
|
7.
Mizukami S. Imaging of caspase-3 activation in HeLa cells stimulation with etoposide using a novel fluorescent probe.
FEBS Lett,1999,453:356-360
|
被引
8
次
|
|
|
|
|
8.
Wu Z. p53-mediated cell cycle arrest and apoptosis induced by shikonin via a caspase-9-dependent mechanism in human malignant melanoma A375-S2 cell death.
J Pharmacol Sci,2004,94:166-176
|
被引
15
次
|
|
|
|
|
9.
Qiao AM. Involvement of mitochondria and caspase pathways in N-demethyl-clarithromycin-induced apoptosis in human cervical cancer HeLa cell.
Acta Pharmacol Sin,2006,27:1622-1629
|
被引
2
次
|
|
|
|
|
10.
Crow MT. Revisiting p53 and its effectors in ischemic heart injury.
Cardiovasc Res,2006,70:401-403
|
被引
2
次
|
|
|
|
|
11.
Oren M. Decision making by p53:life, death and cancer.
Cell Death Differ,2003,10:431-442
|
被引
24
次
|
|
|
|
|
12.
Vousden KH. Live or let die:the cell's response to p53.
Nat Rev Cancer,2002,2:594-604
|
被引
56
次
|
|
|
|
|
13.
Ciciarello M. p53 displacement from centrosomes and p53-mediated G1 arrest following transient inhibition of the mitotic spindle.
J Biol Chem,2001,276:19205-19213
|
被引
9
次
|
|
|
|
|
14.
Karpinich NO. The course of etoposide-induced apoptosis from damage to DNA and p53 activation to mitochondrial release of cytochrome c.
J Biol Chem,2002,277:16547-16552
|
被引
7
次
|
|
|
|
|
15.
Shieh SY. DNA damage induced phosphorylation of p53 alleviates inhibition by MDM2.
Cell,1997,91:325-334
|
被引
29
次
|
|
|
|
|
16.
Canman CE. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53.
Science,1998,281:1677-1679
|
被引
4
次
|
|
|
|
|
17.
Hirao A. DNA damage-induced activation of p53 by the checkpoint kinase Chk2.
Science,2000,287:1824-1827
|
被引
20
次
|
|
|
|
|
18.
Lee TK. FTY720 induces apoptosis of human hepatoma cell lines through PI3-K-mediated Akt dephosphorylation.
Carcinogenesis,2004,25:2397-2405
|
被引
1
次
|
|
|
|
|
19.
McCubrey JA. Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance.
Advan Enzyme Regul,2006,46:249-279
|
被引
30
次
|
|
|
|
|
20.
Kalkman HO. The role of the phosphatidylinositide 3-kinase-protein kinase B pathway in schizophrenia.
Pharmacol Therapeut,2006,110:117-134
|
被引
3
次
|
|
|
|
|
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