全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

木犀草素诱导非小细胞肺癌细胞株A549凋亡和G2周期阻滞

Keywords: 非小细胞肺癌,A549,木犀草素,细胞周期,细胞凋亡

Full-Text   Cite this paper   Add to My Lib

Abstract:

目的:研究木犀草素诱导非小细胞肺癌细胞株A549细胞凋亡和抑制其细胞周期(G2期)的分子机制。方法:MTT法分析木犀草素对A549细胞的生长抑制作用和半数抑制率IC50。Hoechst33258核染色,AnnexinV-FITC/PI双染,流式细胞术检测细胞周期和凋亡,Westernblot分析木犀草素引起的周期相关蛋白和凋亡相关蛋白的变化。Westernblot和免疫细胞化学推测可能存在的分子机制。结果:木犀草素对A549细胞有显著的生长抑制作用,48h的IC50为45.2μmol·L-1,流式细胞术检测细胞周期发现A549细胞经木犀草素处理后主要阻滞在G2期,周期蛋白cyclinA,p-CDC2和p-Rb都呈低表达。Hoechst33258核染色,AnnexinV-FITC/PI双染发现木犀草素处理组细胞凋亡率明显高于未处理组。Westernblot发现木犀草素可上调JNK的磷酸化,下调NF-κB(p65)的磷酸化水平。免疫细胞化学显示木犀草素可抑制TNF-α刺激的p65入核,抑制其入核发挥转录因子的作用,促进细胞凋亡。结论:木犀草素能显著诱导人非小细胞肺癌细胞A549细胞凋亡和细胞周期阻滞,其可能的分子机制是通过上调JNK磷酸化继而激活线粒体凋亡途径,同时抑制NF-κB入核使其不能发挥转录活性。

References

[1]  Stewart D J. Lung cancer: prevention, management, and emerging therapies[M]. New York: Humana Press, 2010: 227.
[2]  Ramos S. Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention[J]. J Nutr Biochem, 2007, 18(7): 427.
[3]  Moon Y J, Wang X, Morris M E. Dietary flavonoids: effects on xenobiotic and carcinogen metabolism[J]. Toxicol In Vitro, 2006, 20(2): 187.
[4]  Zhang Q, Zhao X H, Wang Z J. Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis[J]. Toxicol In Vitro, 2009, 23(5): 797.
[5]  Sasaki N. Protective effects of flavonoids on the cytotoxicity of linoleic acid hydroperoxide toward rat pheochromocytoma PC12 cells[J]. Chemi Biol Interact, 2003, 145(1): 101.
[6]  Brown J E. Structural dependence of flavonoid interactions with Cu2+ ions: implications for their antioxidant properties[J]. Biochem J, 1998, 330 (3): 1173.
[7]  Galati G. Peroxidative metabolism of apigenin and naringenin versus luteolin and quercetin: glutathione oxidation and conjugation[J]. Free Radic Biol Med, 2001, 30(4): 370.
[8]  Shi R X, Ong C N, Shen H M. Luteolin sensitizes tumor necrosis factor-alpha-induced apoptosis in human tumor cells[J]. Oncogene, 2004, 23(46): 7712.
[9]  Shi R X, Ong C N, Shen H M. Protein kinase C inhibition and x-linked inhibitor of apoptosis protein degradation contribute to the sensitization effect of luteolin on tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in cancer cells[J]. Cancer Res, 2005, 65(17): 7815.
[10]  Li X. Chrysin promotes tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induced apoptosis in human cancer cell lines[J]. Toxicol In Vitro, 2011, 25(3): 630.
[11]  Ishikawa Y, Kitamura M. Dual potential of extracellular signal-regulated kinase for the control of cell survival[J]. Biochem Biophys Res Commun, 1999, 264(3): 696.
[12]  Ichijo H. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways[J]. Science, 1997, 275(5296): 90.
[13]  Jang S, Kelley K W, Johnson R W. Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1[J]. Proc Natl Acad Sci USA, 2008, 105(21): 7534.
[14]  Kimata M. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells[J]. Clin Exp Allergy, 2000, 30(4): 501.
[15]  Ando C. Luteolin, a food-derived flavonoid, suppresses adipocyte-dependent activation of macrophages by inhibiting JNK activation[J]. FEBS Lett, 2009, 583(22): 3649.
[16]  Nagata S. Apoptosis by death factor[J]. Cell, 1997, 88(3): 355.
[17]  Chiang C T, Way T D, Lin J K. Sensitizing HER2-overexpressing cancer cells to luteolin-induced apoptosis through suppressing p21(WAF1/CIP1) expression with rapamycin[J]. Mol Cancer Ther, 2007, 6(7): 2127.
[18]  Bagli E. Luteolin inhibits vascular endothelial growth factor-induced angiogenesis: inhibition of endothelial cell survival and proliferation by targeting phosphatidylinositol 3\'-kinase activity[J]. Cancer Res, 2004, 64(21): 7936.
[19]  Hertog M G. Intake of potentially anticarcinogenic flavonoids and their determinants in adults in the Netherlands[J]. Nutr Cancer, 1993, 20(1): 21.
[20]  Ashokkumar P, Sudhandiran G. Protective role of luteolin on the status of lipid peroxidation and antioxidant defense against azoxymethane-induced experimental colon carcinogenesis[J]. Biomed Pharmacother, 2008, 62(9): 590.
[21]  Shi R. Luteolin sensitizes the anticancer effect of cisplatin via c-Jun NH2-terminal kinase-mediated p53 phosphorylation and stabilization[J]. Mol Cancer Ther, 2007, 6(4): 1338.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133