Celastrol suppresses breast cancer MCF-7 cell viability via the AMP-activated protein kinase (AMPK)-induced p53 polo like kinase 2 (PLK-2) pathway
- Authors
- 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
- Issue Date
- 4월-2013
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- AMPK; Breast tumor; Celastrol; p53; PKCzeta; PLK-2
- Citation
- CELLULAR SIGNALLING, v.25, no.4, pp.805 - 813
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELLULAR SIGNALLING
- Volume
- 25
- Number
- 4
- Start Page
- 805
- End Page
- 813
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/103662
- DOI
- 10.1016/j.cellsig.2012.12.005
- ISSN
- 0898-6568
- 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 antitumor effects on MCF-7 cells via AMPK-induced p53 and PLK-2 pathways. (C) 2013 Elsevier Inc. All rights reserved.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.