Prostaglandin A2 and delta 12-prostaglandin J2 induce apoptosis in L1210 cells.
Treatment of L1210 cells with prostaglandin A2 (PGA2) or 9-deoxy-delta 9,12-13,14-dihydro PGD2 (delta 12-PGJ2) resulted in significant G2/M arrest and subsequent DNA fragmentation at concentrations that are cytotoxic to the cells. On agarose gel electrophoresis, DNA ladder formation was evident 24 h after the addition of delta 12-PGJ2 and remained apparent through 72 h, whereas G2/M accumulation was observed 6 h after the treatment. When the morphology of cells was examined by electron microscopy, L1210 cells incubated with a cytotoxic dose of PGA2 or delta 12-PGJ2 for 24 h showed the characteristic morphological features of apoptosis such as chromatin condensation, nuclear fragmentation and formation of apoptotic body. Cycloheximide blocked the DNA fragmentation and morphological changes induced by delta 12-PGJ2. Our results suggest that these cyclopentenone PGs caused apoptotic cell death of L1210 cells which is preceded by G2/M accumulation and requires de novo protein synthesis.
Kim
I K
IK
Department of Biochemistry, Catholic University Medical College, Seoul, South Korea.
Lee
J H
JH
Sohn
H W
HW
Kim
H S
HS
Kim
S H
SH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000302:isolation & purification; D004587:Electrophoresis, Agar Gel; D007700:Kinetics; D007939:Leukemia L1210; D051379:Mice; D008854:Microscopy, Electron; D008970:Molecular Weight; D015230:Prostaglandin D2 / Q000494:pharmacology* / Q000031:analogs & derivatives; D011454:Prostaglandins A / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002843:Chromatin; D004273:DNA, Neoplasm; D011454:Prostaglandins A; C040810:9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydroprostaglandin D2; D003513:Cycloheximide; C100008:prostaglandin A2; D015230:Prostaglandin D2