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

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

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
Volume25
Issue number4
DOIs
Publication statusPublished - 2013 Apr

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

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