Document Detail

Pisiferdiol and pisiferic acid isolated from Chamaecyparis pisifera activate protein phosphatase 2C in vitro and induce caspase-3/7-dependent apoptosis via dephosphorylation of Bad in HL60 cells.
MedLine Citation:
PMID:  20153620     Owner:  NLM     Status:  MEDLINE    
Protein phosphatase 2C (PP2C) dephosphorylates a broad range of substrates and regulates apoptosis, stress response and growth-related pathways. In the course of screening for PP2C activators from natural sources, we isolated abietane-type diterpenes, pisiferdiol and pisiferic acid from Chamaecyparis pisifera. Pisiferdiol having a unique seven-membered ring showed more specific PP2C activation activity (1.3-fold at 100 microM) than pisiferic acid having a normal six-membered ring and oleic acid, which is known to activate PP2C. Pisiferdiol and pisiferic acid showed mixed-type activation with respect to alpha-casein, and this differed from the non-competitive activation of oleic acid in vitro. In vivo, the cytotoxicity of pisiferdiol toward human promyelocytic leukemia cell line HL60 with an IC(50) value of 18.3 microM was 2-fold and 7-fold stronger than those of pisiferic acid and oleic acid, and pisiferdiol induced apoptosis through a caspase 3/7-dependent mechanism involving the dephosphorylation of Bad(1), which is a PP2C substrate. We thus conclude that pisiferdiol and pisiferic acid are novel PP2C activators, and the more specific activator, pisiferdiol, may be a useful chemical probe to study PP2C-mediated signaling pathways, and a lead compound for pharmaceutical agents.
N Aburai; M Yoshida; M Ohnishi; K Kimura
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-12
Journal Detail:
Title:  Phytomedicine : international journal of phytotherapy and phytopharmacology     Volume:  17     ISSN:  1618-095X     ISO Abbreviation:  Phytomedicine     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-15     Completed Date:  2010-12-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9438794     Medline TA:  Phytomedicine     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  782-8     Citation Subset:  IM    
Copyright Information:
2010 Elsevier GmbH. All rights reserved.
Laboratory of Chemical Biology, The United Graduate School of Agricultural Sciences, Iwate University, Morioka, Iwate 020-8550, Japan.
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MeSH Terms
Apoptosis / drug effects*
Caspase 3 / metabolism*
Caspase 7 / metabolism*
Chamaecyparis / chemistry*
Diterpenes / isolation & purification,  pharmacology*
Electrophoresis, Polyacrylamide Gel
Enzyme Activation
HL-60 Cells
Magnetic Resonance Spectroscopy
Phosphoprotein Phosphatases / metabolism*
Spectrometry, Mass, Electrospray Ionization
Spectrophotometry, Ultraviolet
bcl-Associated Death Protein / metabolism*
Reg. No./Substance:
0/Diterpenes; 0/bcl-Associated Death Protein; 67494-15-9/pisiferic acid; EC Phosphatases; EC phosphatase 2C; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7

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