Modulation of cell growth and PPARγ expression in human colorectal cancer cell lines by ciglitazone

Studies have shown that ligand activation of peroxisome proliferator-activated receptor γ (PPARγ) can induce differentiation and inhibit proliferation of several cancer cells. The present study was performed to investigate the effects of the PPARγ ligand, ciglitazone, and the involvement of PPARγ in modulating the growth of human colorectal cancer cells. Lactate dehydrogenase release assay showed that ciglitazone potently inhibited HT-29 (well-differentiated) and COLO-205 (poorly differentiated) colorectal adenocarcinoma cell growth. Measurement of apoptosis by flow cytometry using a fluorescein-conjugated monoclonal antibody against cytokeratin 18 revealed a high induction of apoptosis by ciglitazone in a time-dependent fashion. The expression of PPARγ1 but not PPARγ2 mRNA was significantly downregulated as measured by real-time quantitative PCR, and the PPARγ protein levels were decreased as determined by Western blot analysis. We conclude that ciglitazone treatment suppressed colon cancer cell growth via induction of apoptosis. However, the anticancer effects of ciglitazone may not depend solely on PPARγ activation.