Cheliensisin A Inhibits EGF-Induced Cell Transformation with Stabilization of p53 Protein Via a Hydrogen Peroxide/Chk1-Dependent Axis

	Cheliensisin A Inhibits EGF-Induced Cell Transformation with Stabilization of p53 Protein Via a Hydrogen Peroxide/Chk1-Dependent Axis
	Zhang, Jingjie 1; Gao, Guangxun 1; Chen, Liang 1; Deng, Xu 2,3; Li, Jingxia 1; Yu, Yonghui 1; Zhang, Dongyun 1; Li, Fei 1; Zhang, Min 1; Zhao, Qinshi2,3 ; Huang, Chuanshu 1
	2013-09-01
发表期刊	CANCER PREVENTION RESEARCH
ISSN	1940-6207
卷号	6 期号:9 页码:949-958
摘要	Celiensisin A (Chel A), a novel styryl-lactone isolated from Goniothalamus cheliensis Hu, has been shown to induce apoptosis in human promyelocytic leukemia HL-60 cells with Bcl-2 downregulation. Yet, the potential chemopreventive effect of Chel A has not been explored. Here, we showed that Chel A treatment with various concentrations (0.5, 1.0, 2.0, and 4.0 mu mol/L) for 3 weeks could dramatically inhibit EGF-induced cell transformation in Cl41 cells (IC50 similar to 2.0 mu mol/L). Also, coincubation of Cl41 cells with Chel A (2.0 and 4.0 mu mol/L) for 48 hours could induce cell apoptosis in a caspase-3-dependent manner. Mechanically, Chel A treatment could result in increased p53 phosphorylation at Ser15 and elevated p53 total protein expression. Moreover, we found that p53 induction by Chel A was regulated at the protein degradation level, but not at either the transcription or the mRNA level. Further studies showed that p53 stabilization by Chel A was mediated via induction of phosphorylation and activation of Chk1 protein at Ser345. This notion was substantiated by the results that transfection of dominant negative mutant of Chk1 (GFP-Chk1 D130A) significantly attenuated the p53 protein expression, cell apoptosis, and inhibition of cell transformation by Chel A. Finally, increased hydrogen peroxide was found to mediate Chk1 phosphorylation at Ser345, p53 protein induction, cell apoptotic induction, and transformation inhibition following Chel A treatment. Taken together, our studies identify Chel A as a chemopreventive agent with the understanding of the molecular mechanisms involved. Cancer Prev Res; 6(9); 949-58. (C)2013 AACR.
关键词	Dna-damage Cancer Chemoprevention Induced Phosphorylation Activation Apoptosis Expression Induction Hyperoxia Therapy Roles
资助信息	NIH/NCI [RO1 CA112557, R01 CA177665]; NIH/NIEHS [ES000260, NSFC81229002]; NSFC [90813004]
收录类别	SCI
语种	英语
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/16669
专题	植物化学与西部植物资源持续利用国家重点实验室
作者单位	1.NYU, Sch Med, Nelson Inst Environm Med, Tuxedo Pk, NY 10987 USA 2.Chinese Acad Sci, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650204, Peoples R China 3.Chinese Acad Sci, Kunming Inst Bot, Kunming 650204, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Jingjie,Gao, Guangxun,Chen, Liang,et al. Cheliensisin A Inhibits EGF-Induced Cell Transformation with Stabilization of p53 Protein Via a Hydrogen Peroxide/Chk1-Dependent Axis[J]. CANCER PREVENTION RESEARCH,2013,6(9):949-958.
APA	Zhang, Jingjie.,Gao, Guangxun.,Chen, Liang.,Deng, Xu.,Li, Jingxia.,...&Huang, Chuanshu.(2013).Cheliensisin A Inhibits EGF-Induced Cell Transformation with Stabilization of p53 Protein Via a Hydrogen Peroxide/Chk1-Dependent Axis.CANCER PREVENTION RESEARCH,6(9),949-958.
MLA	Zhang, Jingjie,et al."Cheliensisin A Inhibits EGF-Induced Cell Transformation with Stabilization of p53 Protein Via a Hydrogen Peroxide/Chk1-Dependent Axis".CANCER PREVENTION RESEARCH 6.9(2013):949-958.

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