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

Abstract

Cyclopentenone prostaglandin 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)), which is generated from the dehydration of PGD(2), 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-PGJ(2) 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-PGJ(2) in A549 cells. Results showed that 15d-PGJ(2) 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-PGJ(2)-induced apoptotic processes. These results suggest that 15d-PGJ(2) 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.