Effects of 15-deoxy-Δ12, 14 prostaglandin J2 and ciglitazone on human cancer cell cycle progression and death: The role of PPARγ

The role of PPARγ in ciglitazone and 15-d PGJ2-induced apoptosis and cell cycle arrest of Jurkat (before and after PPARγ gene silencing), U937 (express high levels of PPARγ) and HeLa (that express very low levels of PPARγ) cells was investigated. PPARγ gene silencing, per se, induced a G2/M cell arrest, loss of membrane integrity and DNA fragmentation of Jurkat cells, indicating that PPARγ is important for this cell survival and proliferation. Ciglitazone-induced apoptosis was abolished after knockdown of PPARγ suggesting a PPARγ-dependent pro-apoptotic effect. However, ciglitazone treatment was toxic for U937 and HeLa cells regardless of the presence of PPARγ. This treatment did not change the cell cycle distribution corroborating with a PPARγ-independent mechanism. On the other hand, 15-d PGJ2 induced apoptosis of the three cancer cell lines regardless of the expression of PPARγ. These results suggest that PPARγ plays an important role for death of malignant T lymphocytes (Jurkat cells) and PPARγ agonists exert their effects through PPARγ-dependent and -independent mechanisms depending on the drug and the cell type.