Induction of apoptosis by 15d-PGJ2 via ROS formation: An alternative pathway without PPARγ activation in non-small cell lung carcinoma A549 cells

Cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), which is generated from the dehydration of PGD2, is a natural ligand of peroxisome proliferator-activated receptor gamma (PPARγ) and a potential apoptotic mediator. The synthetic PPARγ ligands, troglitazone and ciglitazone, inhibit tumor progression in many cells by PPARγ activation, but the mechanism of 15d-PGJ2 is still unclear. In this study, GW9662, an antagonist of PPARγ, and quercetin, a natural antioxidant, were used to study the apoptotic mechanism of 15d-PGJ2 in A549 cells. Results showed that 15d-PGJ2 induced apoptosis, which was associated with the production of reactive oxygen species (ROS) and the decrease of GSH levels. Furthermore, quercetin reduced the activity of caspases in 15d-PGJ2-induced apoptotic processes. These results suggest that 15d-PGJ2 induces apoptosis in A549 cells mainly through the formation of ROS; it does not depend on PPARγ activation. Moreover, these findings support the use of quercetin and PPARγ agonists in non-small cell lung carcinoma.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 15d-PGJ2 induces apoptosis in A549 cells via ROS formation. ► The induced apoptosis in A549 cells is through PPARγ-independent pathway. ► The PPARγ-independent pathway is mainly related to intrinsic caspase cascade.