Activation of peroxisome-proliferator activated receptor-gamma (PPARγ) is associated with changes in NF-κB activity and Bcl-2 expression in human colon cancer

Abstract

Background: Peroxisome-proliferator activated receptor-gamma (PPAR~/) is known to induce apoptosis in most cell types. Though PPAR~/expression is increased in colon cancer, the consequence of PPAR~, activation remains obscured. Methods: Human colon cell line (HT29) was treated with a specific PPAR~/ligand, 15dPGJ2. The degree of apoptosis (determined by morphological changes and DNA ladder assay), the level of Bcl-2 expression and NF-KB activity were studied. Immunohistochemistry staining of PPAR-./and Bcl-2 protein were performed on 10 pairs of human colon cancer and normal tissue sections. The In Situ TUNEL technique was used to detect apoptosis in these tissue sections. Results: 15dPGJ2 induced apoptosis in HT-29 in a concentration-dependent manner. Apoptosis could be detected at 8 hr and full DNA breakdown occurred at 24 hr. Treatment with 15dPGJ2 also led to decrease in NF-KB activity (detectable at 4 hr) and Bcl-2 protein expression (detectable at 8 hr). The apoptotic effect of 15dPGJ2 could be partially counteracted by Bcl-2 transfeetion. Both PPAR~/ and Bcl-2 protein were over-exprassed in human colon cancer tissues. However, increased PPAR',/expression was not associated with apoptosis in these tissue sections. Conclusions: Over-expression of PPAR'y may serve as a phenotypic marker of human colon cancer. The lack of apoptosis in human colon cancer tissue might be explained by increased Bcl-2 expression as Bcl-2 transfection protected human colon cells from the apoptotic effect of PPAR~/ligand. Our data suggested that a PPAR~/-Bcl-2 feedback loop may function to control the life-death continuum in colonic cells.