Structural requirements of cyclopentenone prostaglandins to induce endothelial cell apoptosis

Abstract

Prostaglandins are a family of structurally related molecules formed by many cells in response to extrinsic stimuli. A member of this family, 15-deoxy-Δ 12,14-PGJ 2 (15d-PGJ 2), shows unique biological properties including anti-inflammatory, anti-viral, and anti-tumour activity, and has attracted much attention as a high affinity ligand for the peroxisome proliferator-activated receptor γ. Increasing evidence points to additional effects. We investigated several structurally related prostaglandins in comparison to 15d-PGJ 2 with respect to their apoptosis-inducing capacity in human umbilical endothelial cells (HUVEC). Cell viability was tested with a modified MTT assay and apoptosis was detected by Annexin V staining and cell cycle analysis by flow cytometry. Incubation of confluent HUVECs with 15d-PGJ 2 markedly reduced endothelial cell viability which was due to apoptosis. In contrast, none of the other PGs tested affected cell viability. Interestingly, the cyclopentenone ring alone dose-dependently reduced cell viability and significantly induced apoptosis in HUVECs with as low a concentration as 0.25 μM. In conclusion, we report that the cyclopentenone moiety of cyPGs is an essential component for the apoptosis-inducing properties of 15d-PGJ 2. For 15d-PGJ 2 the position of the cyclopentenone ring in conjunction with the side chains yields a molecule with unique biological properties.