Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1-AKT interaction

Xian Ying Fang, Wei Chen, Jun Ting Fan, Ran Song, Lu Wang, Yan Hong Gu, Guang Zhi Zeng, Yan Shen, Xue Feng Wu, Ning Hua Tan*, Qiang Xu, Yang Sun

*Corresponding author for this work

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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 mitochondrial 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.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalToxicology and Applied Pharmacology
Volume267
Issue number1
DOIs
StatePublished - Feb 5 2013

Keywords

  • Breast cancer
  • Cyclopeptide
  • Mitochondrial apoptosis pathway
  • PI3K/AKT
  • RA-V

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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