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

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.