Troglitazone

A PPARγ activator that has antidiabetic, anti-tumor and anti-inflammatory activities; binds to PPARγ and selectively induces the early growth response-1 gene expression; inhibits biosynthesis of cholesterol in CHO cell (IC50=8 ug/ml); enhances human lung cancer cells to TRAIL-induced apoptosis via autophagy flux.Diabetes Approved(In Vitro):Troglitazone is a PPARγ agonist, with EC50s of 550 nM and 780 nM for human and murine PPARγ receptor, respectively. Troglitazone (2-200 μM) is cytotoxic to the pancreatic cancer cell lines (MIA Paca2 and PANC-1 cells), with IC50s of 49.9 ± 1.2 and 51.3 ± 5.3 μM, respectively. Troglitazone (50 μM) increases chromatin condensation in MIA Paca2 and PANC-1 cells, enhances the activity of caspase-3 and decreases Bcl-2 expression. Troglitazone (0, 1, 2, and 4 μM) sensitizes TRAIL-mediated apoptosis in human lung adenocarcinoma cells. Troglitazone enhancement of TRAIL-induced apoptosis is blocked by inhibition of autophagy, via activation of autophagy flux. In addition, the effects of troglitazone are induced by PPARγ activation in A549 cells.(In Vivo):Troglitazone (200 mg/kg, p.o.) shows inhibitory effects on the growth of tumor in the MIA Paca2 xenograft model.