Document Detail


4-O-methylhonokiol, a PPARγ agonist, inhibits prostate tumour growth: p21-mediated suppression of NF-κB activity.
MedLine Citation:
PMID:  23043610     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: The effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, were investigated on human prostate cancer cells and its mechanism of action elucidated.
EXPERIMENTAL APPROACH: The anti-cancer effects of MH were examined in prostate cancer and normal cells. The effects were validated in vivo using a mouse xenograft model.
KEY RESULTS: MH increased the expression of PPARγ in prostate PC-3 and LNCap cells. The pull-down assay and molecular docking study indicated that MH directly binds to PPARγ. MH also increased transcriptional activity of PPARγ but decreased NF-κB activity. MH inhibited the growth of human prostate cancer cells, an effect attenuated by the PPARγ antagonist GW9662. MH induced apoptotic cell death and this was related to G(0) -G(1) phase cell cycle arrest. MH increased the expression of the cell cycle regulator p21, and apoptotic proteins, whereas it decreased phosphorylation of Rb and anti-apoptotic proteins. Transfection of PC3 cells with p21 siRNA or a p21 mutant plasmid on the cyclin D1/ cycline-dependent kinase 4 binding site abolished the effects of MH on cell growth, cell viability and related protein expression. In the animal studies, MH inhibited tumour growth, NF-κB activity and expression of anti-apoptotic proteins, whereas it increased the transcriptional activity and expression of PPARγ, and the expression of apoptotic proteins and p21 in tumour tissues.
CONCLUSIONS AND IMPLICATION: MH inhibits growth of human prostate cancer cells through activation of PPARγ, suppression of NF-κB and arrest of the cell cycle. Thus, MH might be a useful tool for treatment of prostate cancer.
Authors:
N J Lee; J H Oh; J O Ban; J H Shim; H P Lee; J K Jung; B W Ahn; D Y Yoon; S B Han; Y W Ham; J T Hong
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  168     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-21     Completed Date:  2013-08-14     Revised Date:  2014-03-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1133-45     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*,  therapeutic use
Apoptosis / drug effects
Biphenyl Compounds / pharmacology*,  therapeutic use
Cell Cycle Checkpoints / drug effects
Cell Line
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
Humans
Lignans / pharmacology*,  therapeutic use
Male
Mice
Mice, Nude
NF-kappa B / metabolism*
PPAR gamma / agonists*
Prostatic Neoplasms / drug therapy*,  metabolism,  pathology
Tumor Burden / drug effects
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/4-O-methylhonokiol; 0/Antineoplastic Agents; 0/Biphenyl Compounds; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Lignans; 0/NF-kappa B; 0/PPAR gamma
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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