RRC ID 11182
Author Aburai N, Yoshida M, Ohnishi M, Kimura K.
Title 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.
Journal Phytomedicine
Abstract 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.
Volume 17(10)
Pages 782-8
Published 2010-8
DOI 10.1016/j.phymed.2009.12.015
PII S0944-7113(09)00347-X
PMID 20153620
MeSH Apoptosis / drug effects* Caspase 3 / metabolism* Caspase 7 / metabolism* Chamaecyparis / chemistry* Diterpenes / isolation & purification Diterpenes / pharmacology* Electrophoresis, Polyacrylamide Gel Enzyme Activation HL-60 Cells Humans Magnetic Resonance Spectroscopy Phosphoprotein Phosphatases / metabolism* Phosphorylation Protein Phosphatase 2C Spectrometry, Mass, Electrospray Ionization Spectrophotometry, Ultraviolet bcl-Associated Death Protein / metabolism*
IF 3.526
Times Cited 17
WOS Category INTEGRATIVE & COMPLEMENTARY MEDICINE PHARMACOLOGY & PHARMACY PLANT SCIENCES CHEMISTRY, MEDICINAL
Resource
Human and Animal Cells HL-60 (RCB0041)