Document Detail

15-hydroxy-eicosatetraenoic acid arrests growth of colorectal cancer cells via a peroxisome proliferator-activated receptor gamma-dependent pathway.
MedLine Citation:
PMID:  14566836     Owner:  NLM     Status:  MEDLINE    
Peroxisome proliferator-activated receptor gamma (PPARgamma) inhibits cell growth via promoting apoptosis. Human colorectal cancer tissues had abundant PPARgamma but the incidence of apoptosis was very low, suggesting a defect in the PPARgamma pathway. Here, we found that 15-hydroxy-eicosatetraenoic acid (15S-HETE), an endogenous ligand for PPARgamma, was significantly decreased in the serum of patients with colorectal cancer. Treatment of colon cancer cells with 15S-HETE inhibited cell proliferation and induced apoptosis, which was preceded by an increase in TGF-beta-inducible early gene (TIEG) and a decrease in Bcl-2. The action of 15S-HETE could be blocked when PPARgamma was suppressed. Overexpression of Bcl-2 prevented the apoptosis. The levels of TIEG and 15-lipoxygenase (15-LOX), the enzyme responsible for 15S-HETE production, was decreased in colorectal cancer. Therefore, colorectal cancer is associated with decreased 15S-HETE. Treatment of colon cancer cells with 15S-HETE inhibits cell proliferation and induces apoptosis in a PPARgamma-dependent pathway involving augmentation of TIEG and reduction of Bcl-2 expression.
George G Chen; Hu Xu; Janet F Y Lee; Malayannan Subramaniam; Ka L Leung; Su H Wang; Ursula P F Chan; Thomas C Spelsberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  107     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-10-20     Completed Date:  2004-02-18     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  837-43     Citation Subset:  IM    
Copyright Information:
Copyright 2003 Wiley-Liss, Inc.
Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
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MeSH Terms
Apoptosis / drug effects
Cell Division / drug effects*
Cell Survival / drug effects
Colonic Neoplasms / pathology
DNA-Binding Proteins / metabolism
Early Growth Response Transcription Factors
Hydroxyeicosatetraenoic Acids / pharmacology*
Kruppel-Like Transcription Factors
Lipoxygenase / metabolism
Receptors, Cytoplasmic and Nuclear / drug effects,  genetics,  physiology*
Recombinant Proteins / drug effects
Rectal Neoplasms / pathology
Transcription Factors / drug effects,  genetics,  metabolism,  physiology*
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Early Growth Response Transcription Factors; 0/Hydroxyeicosatetraenoic Acids; 0/KLF10 protein, human; 0/Kruppel-Like Transcription Factors; 0/Receptors, Cytoplasmic and Nuclear; 0/Recombinant Proteins; 0/Transcription Factors; 73945-47-8/15-hydroxy-5,8,11,13-eicosatetraenoic acid; EC

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