15-Deoxy-Delta(12,14)-prostaglandin J(2), a ligand for peroxisome proliferator-activated receptor-gamma, induces apoptosis in JEG3 choriocarcinoma cells.
Apoptosis has been described in placental (trophoblast) tissues during both normal and abnormal pregnancies. We have studied the effects of the cyclopentenone prostaglandins (PGs) on trophoblast cell death using JEG3 choriocarcinoma cells. PGJ(2), Delta(12)PGJ(2), and 15-deoxy-Delta(12,14)-PGJ(2) (15dPGJ(2)) (10 microM) significantly reduced mitochondrial activity (MTT assay) over 16 h by 17.4 +/- 4.7%, 28 +/- 9.3%, and 62.5 +/- 2.8%, respectively (mean +/- sem), while PGA(2) and PGD(2) had no effect. The synthetic PPAR-gamma ligand ciglitizone (12.5 microM) had a potency similar to 15dPGJ(2) (69 +/- 3% reduction). Morphological examination of cultures treated with PGJ(2) and its derivatives revealed the presence of numerous cells with dense, pyknotic nuclei, a hallmark of apoptosis. FACS analysis revealed an abundance (approximately 40%) of apoptotic cells after 16-h treatment with 15dPGJ(2) (10 microM). The caspase inhibitor ZVAD-fmk (5 microM) significantly diminished the apoptotic effects of Delta(12)PGJ(2) and 15dPGJ(2). JEG3 cells expressed PPAR-gamma mRNA by Northern analysis. These novel findings imply a role for PPAR-gamma ligands in various processes associated with pregnancy and parturition.
Keelan
J A
JA
Faculty of Medicine and Health Science, University of Auckland School of Medicine, Auckland, New Zealand. j.keelan@auckland.ac.nz
Sato
T A
TA
Marvin
K W
KW
Lander
J
J
Gilmour
R S
RS
Mitchell
M D
MD
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002822:Choriocarcinoma; D015237:Dinoprost / Q000494:pharmacology; D005260:Female; D006801:Humans; D007743:Labor, Obstetric; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000378:metabolism; D011247:Pregnancy; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011454:Prostaglandins A / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000590:Amino Acid Chloromethyl Ketones; D009687:Nuclear Proteins; D011454:Prostaglandins A; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D015237:Dinoprost; C100008:prostaglandin A2; D015230:Prostaglandin D2