Hydrogen peroxide/ATR-Chk2 activation mediates p53 protein stabilization and anti-cancer activity of cheliensisin A in human cancer cells
Zhang, Jingjie1; Gao, Guangxun1,2; Chen, Liang1; Li, Jingxia1; Deng, Xu3; Zhao, Qin-shi3; Huang, Chuanshu1
2014
发表期刊ONCOTARGET
ISSN1949-2553
卷号5期号:3页码:841-852
摘要Cheliensisine A (Chel A) as a novel styryl-lactone isolated from Goniothalamus cheliensis Hu has been indicated to be a chemotherapeutic agent in Leukemia HL-60 cells. However, its potential for cancer treatment and the underlying mechanisms are not deeply investigated to the best of our knowledge. Current studies showed that Chel A could trigger p53-mediated apoptosis, accompanied with dramatically inhibition of anchorage-independent growth of human colon cancer HCT116 cells. Further studies found that Chel A treatment resulted in p53 protein stabilization and accumulation via the induction of its phosphorylation at Ser20 and Ser15. Moreover, Chel A-induced p53 protein accumulation and activation required ATR/Chk2 axis, which is distinct from the mechanism that we have most recently identified the Chk1/p53-dependent apoptotic response by Chel A in normal mouse epidermal Cl41 cells. In addition, our results demonstrated that hydrogen peroxide generation induced by Chel A acted as a precursor for all these signaling events and downstream biological effects. Taken together, we have identified the Chel A as a new therapeutic agent, which highlights its potential for cancer therapeutic effect.
关键词Cheliensisin a Apoptosis Colon Cancer P53 Chemotherapeutic Agent
资助信息NIH/NCI [RO1 CA177665, CA165980, RO1 CA112557]; NIH/NIEHS [ES000260]; [NSFC81229002]; [NSF90813004]
学科领域Oncology ; Cell Biology
收录类别SCI
语种英语
WOS研究方向Oncology ; Cell Biology
WOS类目Oncology ; Cell Biology
WOS记录号WOS:000332701300023
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被引频次:11[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/18052
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.Fourth Mil Med Univ, Xijing Hosp, Dept Hematol, Xian 710032, Shaanxi, Peoples R China
3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Peoples R China
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Zhang, Jingjie,Gao, Guangxun,Chen, Liang,et al. Hydrogen peroxide/ATR-Chk2 activation mediates p53 protein stabilization and anti-cancer activity of cheliensisin A in human cancer cells[J]. ONCOTARGET,2014,5(3):841-852.
APA Zhang, Jingjie.,Gao, Guangxun.,Chen, Liang.,Li, Jingxia.,Deng, Xu.,...&Huang, Chuanshu.(2014).Hydrogen peroxide/ATR-Chk2 activation mediates p53 protein stabilization and anti-cancer activity of cheliensisin A in human cancer cells.ONCOTARGET,5(3),841-852.
MLA Zhang, Jingjie,et al."Hydrogen peroxide/ATR-Chk2 activation mediates p53 protein stabilization and anti-cancer activity of cheliensisin A in human cancer cells".ONCOTARGET 5.3(2014):841-852.
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