Celastrol suppresses breast cancer MCF-7 cell viability via the AMP-activated protein kinase (AMPK)-induced p53-polo like kinase 2 (PLK-2) pathway

Ji Hae Kim, Jung Ok Lee, Soo Kyung Lee, Nami Kim, Ga Young You, Ji Wook Moon, Jie Sha, Su Jin Kim, Sun Hwa Park, Hyeon Soo Kim

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57 Citations (Scopus)


Celastrol, an anti-oxidant flavonoid that is widely distributed in the plant kingdom, has been suggested to have chemopreventive effects on cancer cells: however, the mechanism of this process is not completely understood. In this study, we found that celastrol suppressed the viability of breast cancer MCF-7 cells in an AMP-activated protein kinase (AMPK)-dependent fashion. Celastrol also induced an increase in reactive oxygen species (ROS) levels, leading to AMPK phosphorylation. Protein kinase C (PKC) zeta was also shown to play a role in celastrol-induced ROS generation. In addition, celastrol increased phosphorylation of the pro-apoptotic effector, p53. Inhibition of AMPK blocked celastrol-mediated p53 phosphorylation. Moreover, celastrol increased the expression of tumor suppressor polo like kinase-2 (PLK-2) in a p53-dependent manner. Neither celastrol-induced PLK-2 induction nor celastrol-mediated apoptosis inducing factor poly(ADP-ribose) polymerase-2 (PARP-2) induction was observed in p53 knock-out cells. Furthermore, add-back of PLK-2 resulted in an increase in both celastrol-mediated PARP-2 induction and celastrol-induced apoptotic index sub G1 population. Together, these results suggest that celastrol may have anti-tumor effects on MCF-7 cells via AMPK-induced p53 and PLK-2 pathways.

Original languageEnglish
Pages (from-to)805-813
Number of pages9
JournalCellular Signalling
Issue number4
Publication statusPublished - 2013 Apr

Bibliographical note

Funding Information:
This study was supported by the National Research Foundation of Korea funded by the Korea government ( 2010-0011053 ).


  • AMPK
  • Breast tumor
  • Celastrol
  • P53
  • PKCzeta
  • PLK-2

ASJC Scopus subject areas

  • Cell Biology


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