Troglitazone Induced Apoptosis in a Human Colon Cancer Cell Line

Abstract ID 21111 Poster Board 234 Troglitazone is a member of the thiazolidinedione family which acts primarily through upregulating the peroxisome proliferator-activated receptor (PPAR) pathway. The PPARs are members of the steroid/thyroid nuclear receptor superfamily and is important in coordinating energy systems, including glucose and lipid metabolism. Binding of PPARγ agonists such as troglitazone and other thiazolidinediones results in increased insulin sensitivity and lower glucose levels in patients with type 2 diabetes. Treatment with troglitazone was withdrawn from its usage in type II diabetics due to hepatotoxicity. Studies have linked PPAR receptors to the development of cancer. However, the research is contradictory as to whether these pathways cause tumor genesis or assist with inhibiting cell proliferation. We have examined the effect of troglitazone on HCT116 human colon carcinoma cells. Troglitazone induced cell death was observed at 24hr by concentrations of 50uM or greater. Cell death was confirmed to be apoptosis. Using a Qiagen RT2 Profiler™ PCR Array Human PPAR Targets platform, we identified numerous PPAR targets that have altered expression in HCT116 cells. We have confirmed the expression changes using RT PCR from HCT116 cells treated with troglitazone. Antagonism of PPARalpha and PPARgamma in the presence of troglitazone will be used to determine if apoptosis is being mediated through PPAR activation.