15-hydroxy-5-8-11-13-eicosatetraenoic-acid and Rectal-Neoplasms

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.

Topics: Apoptosis; Cell Division; Cell Survival; Colonic Neoplasms; DNA-Binding Proteins; Early Growth Response Transcription Factors; Humans; Hydroxyeicosatetraenoic Acids; Immunohistochemistry; Kruppel-Like Transcription Factors; Lipoxygenase; Receptors, Cytoplasmic and Nuclear; Recombinant Proteins; Rectal Neoplasms; Transcription Factors; Transfection; Tumor Cells, Cultured