Induction of c-fos protooncogene transcription and apoptosis by delta 12-prostaglandin J2 in human Pl-21 myeloid leukemia and RC-K8 pre-B lymphoma cells.
delta 12-prostaglandin J2 (PGJ2) is a dehydration product of PGD2 and thought to be the most potent antitumor agent among prostaglandin compounds. We examine the cytotoxic effects of PGJ2 on the cell growth of leukemia/lymphoma cells. PGJ2 inhibited the growth of both human PL-21 myeloid leukemia and RC-K8 pre-B lymphoma cells in culture in a dose-dependent manner with fragmentation of nucleus and formation of apoptotic body. Agarose gel electrophoresis revealed DNA ladder formation in the cells treated with PGJ2. Furthermore, PGJ2 induced a rapid and transient expression of apoptosis-related protooncogene, c-fos, in both cells. The gene transcriptional rate was remarkably increased approximately 3.3-fold in PGJ2 treated cells, but the stability of c-fos mRNA was not significantly changed. Inhibition of de novo protein synthesis with cycloheximide increased c-fos mRNA stability but not abrogated PGJ2-induced c-fos transcription. These data suggest that PGJ2 can induce apoptosis of human leukemia/lymphoma cells and the rapid activation of c-fos protooncogene transcription in which de novo protein synthesis is not required.
Higashiyama
K
K
Second Department of Surgery, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Niiya
K
K
Ozawa
T
T
Hayakawa
Y
Y
Fujimaki
M
M
Sakuragawa
N
N
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000737:chemistry / Q000187:drug effects; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C037112:9-deoxy-delta-9-prostaglandin D2; C040810:9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydroprostaglandin D2; D015230:Prostaglandin D2