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

Int J Cancer. 2003 Dec 10;107(5):837-43. doi: 10.1002/ijc.11447.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects
  • Cell Division / drug effects*
  • Cell Survival / drug effects
  • Colonic Neoplasms / pathology
  • DNA-Binding Proteins / metabolism
  • Early Growth Response Transcription Factors
  • Humans
  • Hydroxyeicosatetraenoic Acids / pharmacology*
  • Immunohistochemistry
  • Kruppel-Like Transcription Factors
  • Lipoxygenase / metabolism
  • Receptors, Cytoplasmic and Nuclear / drug effects
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Recombinant Proteins / drug effects
  • Rectal Neoplasms / pathology
  • Transcription Factors / drug effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transfection
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Early Growth Response Transcription Factors
  • Hydroxyeicosatetraenoic Acids
  • KLF10 protein, human
  • Kruppel-Like Transcription Factors
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Proteins
  • Transcription Factors
  • 15-hydroxy-5,8,11,13-eicosatetraenoic acid
  • Lipoxygenase