15-hydroxy-eicosatetraenoic acid arrests growth of colorectal cancer cells via a peroxisome proliferator-activated receptor gamma-dependent pathway
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AbstractPeroxisome 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. (C) 2003 Wiley-Liss, Inc.
All Author(s) ListChen GG, Xu H, Lee JFY, Subramaniam M, Leung KL, Wang SH, Chan UPF, Spelsberg TC
Journal nameINTERNATIONAL JOURNAL OF CANCER
Year2003
Month12
Day10
Volume Number107
Issue Number5
PublisherWILEY-LISS
Pages837 - 843
ISSN0020-7136
eISSN1097-0215
LanguagesEnglish-United Kingdom
Keywords15-lipokygenase; colorectal carcinoma; peroxisome proliferator-activated receptor gamma 15-hydroxy-eicosatetraenoic acid; TGF-beta-inducible early gene and Bcl-2
Web of Science Subject CategoriesOncology; ONCOLOGY

Last updated on 2020-19-01 at 02:45