Celastrol suppresses breast cancer MCF-7 cell viability via the AMP-activated protein kinase (AMPK)-induced p53-polo like kinase 2 (PLK-2) pathway
| Autor: | Ji Hae Kim, Ga Young You, Su Jin Kim, Jung Ok Lee, Hyeon Soo Kim, Nami Kim, Sun Hwa Park, Jie Sha, Ji Wook Moon, Soo Kyung Lee |
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| Rok vydání: | 2012 |
| Předmět: |
Apoptosis
Breast Neoplasms AMP-Activated Protein Kinases Protein Serine-Threonine Kinases chemistry.chemical_compound AMP-activated protein kinase Humans Viability assay Phosphorylation RNA Small Interfering Protein kinase A Protein kinase C Protein Kinase C biology AMPK Cell Biology HCT116 Cells Antineoplastic Agents Phytogenic G1 Phase Cell Cycle Checkpoints Triterpenes Cell biology Biochemistry chemistry Celastrol Cancer cell biology.protein MCF-7 Cells Female RNA Interference Poly(ADP-ribose) Polymerases Tumor Suppressor Protein p53 Pentacyclic Triterpenes Reactive Oxygen Species Signal Transduction |
| Zdroj: | Cellular signalling. 25(4) |
| ISSN: | 1873-3913 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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