15-deoxyprostaglandin-j2 and Lung-Neoplasms

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.

Topics: Apoptosis; Carcinoma, Non-Small-Cell Lung; Caspases; Cell Line, Tumor; Glutathione; Humans; Lung Neoplasms; PPAR gamma; Prostaglandin D2; Quercetin; Reactive Oxygen Species; Thiazolidinediones

Topics: Antineoplastic Agents; Apoptosis; Chromans; Cyclin D1; Humans; Lung Neoplasms; Prostaglandin D2; Proto-Oncogene Proteins p21(ras); Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Thiazolidinediones; Transcription Factors; Troglitazone

To study the expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in lung cancer cells, and to testify if the PPAR-gamma agonists can inhibit human lung cancer cell growth through induction of apoptosis, PPAR-gamma was detected in two lung cancer cell lines by RT-PCR and immunohistochemistry, the inhibition of human lung cancer cell growth was investigated by MTT and cell counts, and the apoptosis was assessed by TUNEL. The results showed that: (1) PPAR-gamma expressed on two lung cancer cell lines; (2) PPAR-gamma activated by ligands could inhibit human lung cancer cell growth remarkably; (3) PPAR-gamma agonists could induce apoptosis to inhibit lung cancer cell growth. It was concluded that PPAR-gamma expressed in lung cancer cell can be activated by ligands and can inhibit lung cancer cell growth through induction of apoptosis.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cell Division; Gene Expression Regulation, Neoplastic; Humans; Ligands; Lung Neoplasms; Prostaglandin D2; Receptors, Cytoplasmic and Nuclear; Transcription Factors; Tumor Cells, Cultured