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

Abstract 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.