Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1-AKT interaction
Fang, Xian-Ying1; Chen, Wei1; Fan, Jun-Ting2; Song, Ran1; Wang, Lu1; Gu, Yan-Hong3; Zeng, Guang-Zhi2; Shen, Yan1; Wu, Xue-Feng1; Tan, Ning-Hua2; Xu, Qiang1; Sun, Yang1
2013-02-15
发表期刊TOXICOLOGY AND APPLIED PHARMACOLOGY
ISSN0041-008X
卷号267期号:1页码:95-103
摘要In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondria] apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells. Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. (C) 2012 Elsevier Inc. All rights reserved.
关键词Ra-v Cyclopeptide Mitochondrial Apoptosis Pathway Pi3k/akt Breast Cancer
资助信息Science Fund for Creative Research Groups of NSFC [81121062]; National Natural Science Foundation of China [90913023, 81173070, 91229109, 91129728, 21102152, U1032602, 91013002]; Science Fund for Creative Research Groups of NSFC(81121062); National Natural Science Foundation of China(90913023; 81173070; 91229109; 91129728; 21102152; U1032602; 91013002)
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/151853/16224
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.Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Sch Life Sci, Nanjing 210008, Jiangsu, Peoples R China
2.Chinese Acad Sci, State Key Lab Phytochem & Plant Resources W China, Kunming Inst Bot, Kunming 650201, Peoples R China
3.Nanjing Med Univ, Dept Clin Oncol, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China
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Fang, Xian-Ying,Chen, Wei,Fan, Jun-Ting,et al. Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1-AKT interaction[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2013,267(1):95-103.
APA Fang, Xian-Ying.,Chen, Wei.,Fan, Jun-Ting.,Song, Ran.,Wang, Lu.,...&Sun, Yang.(2013).Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1-AKT interaction.TOXICOLOGY AND APPLIED PHARMACOLOGY,267(1),95-103.
MLA Fang, Xian-Ying,et al."Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1-AKT interaction".TOXICOLOGY AND APPLIED PHARMACOLOGY 267.1(2013):95-103.
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