Prostaglandins are a family of structurally related molecules formed by many cells in response to extrinsic stimuli. A member of this family, 15-deoxy-Delta(12.14)-PGJ(2) (15d-PGJ(2)), shows unique biological properties including anti-inflammatory, anti-viral, and antitumour activity, and has attracted much attention as a high affinity ligand for the peroxisome proliferator-activated receptor gamma. 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 muM. 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. (C) 2003 Elsevier Inc. All rights reserved.