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 journalArticle

32 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 1

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AMP-Activated Protein Kinases
MCF-7 Cells
Cell Survival
Phosphotransferases
Breast Neoplasms
Poly(ADP-ribose) Polymerases
Phosphorylation
tripterine
Reactive Oxygen Species
Apoptosis Inducing Factor
Neoplasms
Flavonoids
Oxidants

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Celastrol suppresses breast cancer MCF-7 cell viability via the AMP-activated protein kinase (AMPK)-induced p53-polo like kinase 2 (PLK-2) pathway. / Kim, Ji Hae; Lee, Jung Ok; Lee, Soo Kyung; Kim, Nami; You, Ga Young; Moon, Ji Wook; Sha, Jie; Kim, Su Jin; Park, Sun-Hwa; Kim, Hyeon Soo.

In: Cellular Signalling, Vol. 25, No. 4, 01.04.2013, p. 805-813.

Research output: Contribution to journalArticle

Kim, Ji Hae ; Lee, Jung Ok ; Lee, Soo Kyung ; Kim, Nami ; You, Ga Young ; Moon, Ji Wook ; Sha, Jie ; Kim, Su Jin ; Park, Sun-Hwa ; Kim, Hyeon Soo. / Celastrol suppresses breast cancer MCF-7 cell viability via the AMP-activated protein kinase (AMPK)-induced p53-polo like kinase 2 (PLK-2) pathway. In: Cellular Signalling. 2013 ; Vol. 25, No. 4. pp. 805-813.
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