Influence of 17β-Estradiol on 15-Deoxy-Δ12,14 Prostaglandin J2 -Induced Apoptosis in MCF-7 and MDA-MB-231 Cells


The nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ), is expressed in variouscancer cells including breast, prostate, colorectal and cervical examples. An endogenous ligand of PPARγ,15-deoxy-Δ12,14 prostaglandin J2 (PGJ2), is emerging as a potent anticancer agent but the exact mechanismhas not been fully elucidated, especially in breast cancer. The present study compared the anticancer effects ofPGJ2 on estrogen receptor alpha (ERα)-positive (MCF-7) and ERα-negative (MDA-MB-231) human breastcancer cells. Based on the reported signalling cross-talk between PPARγ and ERα, the effect of the ERα ligand,17β-estradiol (E2) on the anticancer activities of PGJ2 in both types of cells was also explored. Here we reportthat PGJ2 inhibited proliferation of both MCF-7 and MDA-MB-231 cells by inducing apoptotic cell death withactive involvement of mitochondria. The presence of E2 potentiated PGJ2-induced apoptosis in MCF-7, but notin MDA-MB-231 cells. The PPARγ antagonist, GW9662, failed to block PGJ2-induced activities but potentiatedits effects in MCF-7 cells, instead. Interestingly, GW9662 also proved capable of inducing apoptotic cell death.It can be concluded that E2 enhances PPARγ-independent anticancer effects of PGJ2 in the presence of itsreceptor.