Differential effects of serum constituents on apoptosis induced by the cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) in WISH epithelial cells

Cyclopentenone prostaglandins, Delta(12)-PGJ(2) and 15d-PGJ(2), have potent anti-tumour and anti-inflammatory activities, and have been shown to induce apoptosis in amnion-derived WISH cells. In this study, we have investigated the protective effects of serum and its constituents (growth factors and albumin) on Delta(12) -PGJ(2) and 15d-PGJ(2)-induced apoptosis in WISH cells. Serum (0.5% w/v) was protective against both A 12 -PGJ(2) and 15d-PGJ2-induced apoptosis. This was not due to the presence of serum-derived growth factors (EGF, IGF-1 and IGF-2), since they had no significant effect on 15d-PGJ(2)-induced cell death. In contrast, IGF-1 partially inhibited etoposide-induced apoptosis, confirming the presence of a functional IGF-1 receptor signalling system. Albumin was identified as the key survival factor in serum, since albumin and delipidated albumin exhibited the same level of protection from 15d-PGJ(2)-induced apoptosis as serum itself. The potential for serum albumin to regulate the bioactivity of cyclopentenone PGs may be of considerable importance in pathological conditions where roles for cyclopentenone PGs have been identified. (C) 2004 Elsevier Ltd. All rights reserved

15-deoxy-Delta(12,14)-prostaglandin J(2)-induced apoptosis in amnion-like WISH cells

Apoptosis at the site of rupture has been proposed to play a role in premature rupture of the fetal membranes, a condition associated with increased risk of neonatal sepsis and preterm birth. We investigated the ability of peroxisome proliferator-activated receptor (PPAR)-gamma ligands 15-deoxy-Delta(12,14)PGJ(2) (15d-PGJ(2)), Delta(12)PGJ2(,) ciglitizone and rosiglitazone to induce apoptosis in the amnion-like WISH cell line. 15d-PGJ(2) (10 muM) induced morphological characteristics of apoptosis within 2 h, with biochemical indices (caspase activation and substrate cleavage) following shortly after; maximum cell death (approximately 60%) was observed by 16 h, with an EC50 of approximately 7 muM 15d-PGJ(2). Delta(12)-PGJ(2) also induced apoptosis but was less potent and acted at a much slower rate. While ciglitizone also induced apoptosis, rosiglitazone had no effect on cell viability. The mechanism of induction of apoptosis by 15d-PGJ(2) and Delta(12)PGJ(2), which may be independent of PPAR-gamma activation, requires further elucidation. (C) 2001 Elsevier Science Inc. All rights reserved