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PMID: 22298641 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Curcumin inhibits protein phosphatases 2A and 5, leading to activation of mitogen-activated protein kinases and death in tumor cells.

Carcinogenesis ·Vol. 33 ·No. 4 ·2012-04-00 ·Pages 868-75

Han X, Xu B, Beevers CS, Odaka Y, Chen L, Liu L, Luo Y, Zhou H, Chen W, Shen T, Huang S

Abstract

Curcumin can induce p53-independent apoptosis. However, the underlying mechanism remains to be defined. Here, we show that curcumin-induced apoptosis in a panel of tumor cells with mutant p53. Curcumin rapidly induced activation of the mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (Erk1/2) and c-Jun N-terminal kinase (JNK). Inhibition of JNK (with SP600125) or Erk1/2 (with U0126) partially prevented curcumin-induced cell death in the cells. Similarly, expression of dominant negative c-Jun or downregulation of Erk1/2 in part attenuated curcumin-induced cell death. It appears that curcumin-induced activation of MAPKs and apoptosis was due to induction of reactive oxygen species (ROS), as pretreatment with N-acetyl-L-cysteine, a ROS scavenger, blocked these events. Furthermore, we found that curcumin-induced activation of MAPK pathways was related to inhibition of the serine/threonine protein phosphatases 2A (PP2A) and 5 (PP5). Overexpression of PP2A or PP5 partially prevented curcumin-induced activation of JNK and Erk1/2 phosphorylation as well as cell death. The results suggest that curcumin induction of ROS activates MAPKs, at least partially by inhibiting PP2A and PP5, thereby leading to p53-independent apoptosis in tumor cells.

MeSH Terms
Apoptosis/drug effects Cell Line, Tumor Curcumin/pharmacology Enzyme Activation Enzyme Inhibitors/pharmacology Humans Mitogen-Activated Protein Kinases/metabolism Nuclear Proteins/antagonists & inhibitors Phosphoprotein Phosphatases/antagonists & inhibitors Protein Phosphatase 2/antagonists & inhibitors
Chemicals
Enzyme Inhibitors Nuclear Proteins Mitogen-Activated Protein Kinases Phosphoprotein Phosphatases Protein Phosphatase 2 protein phosphatase 5 Curcumin
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Han Xiuzhen
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, Shandong Province, People's Republic of China.
Xu Baoshan
Beevers Christopher S
Odaka Yoshinobu
Chen Long
Liu Lei
Luo Yan
Zhou Hongyu
Chen Wenxing
Shen Tao
Huang Shile
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Article Info
Journal
Carcinogenesis
Abbr.
Carcinogenesis
ISSN
1460-2180
DOI
10.1093/carcin/bgs029
Published
2012-04-00
Epub
2012-00-31
Pages
868-75
Language
English
Region
England
NLM ID
8008055
PMCID
PMC3324444
Subset
IM
Grants
NCI NIH HHS · CA115414 · United States
External Links
PubMed source DOI: 10.1093/carcin/bgs029 PMC Full Text View journal details
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