15‐hydroxy‐eicosatetraenoic acid arrests growth of colorectal cancer cells via a peroxisome proliferator‐activated receptor gamma‐dependent pathway

• Published in: International journal of cancer 2003-12, Vol.107 (5), p.837-843
• Main Authors: Chen, George G., Xu, Hu, Lee, Janet F.Y., Subramaniam, Malayannan, Leung, Ka L., Wang, Su H., Chan, Ursula P.F., Spelsberg, Thomas C.
• Format: Article
• Language: English
• Subjects: 15‐hydroxy‐eicosatetraenoic acid; 15‐lipoxygenase; Apoptosis - drug effects; Biological and medical sciences; Cell Division - drug effects; Cell Survival - drug effects; Colonic Neoplasms - pathology; colorectal carcinoma; DNA-Binding Proteins - metabolism; Early Growth Response Transcription Factors; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Hydroxyeicosatetraenoic Acids - pharmacology; Immunohistochemistry; Kruppel-Like Transcription Factors; Lipoxygenase - metabolism; Medical sciences; peroxisome proliferator‐activated receptor gamma; Receptors, Cytoplasmic and Nuclear - drug effects; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - physiology; Recombinant Proteins - drug effects; Rectal Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; TGF‐β‐inducible early gene and Bcl‐2; Transcription Factors - drug effects; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology; Transfection; Tumor Cells, Cultured; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.11447

Peroxisome proliferator‐activated receptor gamma (PPARγ) inhibits cell growth via promoting apoptosis. Human colorectal cancer tissues had abundant PPARγ but the incidence of apoptosis was very low, suggesting a defect in the PPARγ pathway. Here, we found that 15‐hydroxy‐eicosatetraenoic acid (15S‐HETE), an endogenous ligand for PPARγ, 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‐β‐inducible early gene (TIEG) and a decrease in Bcl‐2. The action of 15S‐HETE could be blocked when PPARγ 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 PPARγ‐dependent pathway involving augmentation of TIEG and reduction of Bcl‐2 expression. © 2003 Wiley‐Liss, Inc.