INDUCTION OF C-FOS PROTOONCOGENE TRANSCRIPTION AND APOPTOSIS BY DELTA(12)-PROSTAGLANDIN J(2) IN HUMAN PL-21 MYELOID-LEUKEMIA AND RC-K8 PRE-B LYMPHOMA-CELLS

Delta(12)-prostaglandin J(2) (PGJ(2)) is a dehydration product of PGD( 2) and thought to be the most potent antitumor agent among prostagland in compounds. We examine the cytotoxic effects of PGJ(2) on the cell g rowth of leukemia/lymphoma cells. PGJ(2) 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 formatio n of apoptotic body. Agarose gel electrophoresis revealed DNA ladder f ormation in the cells treated with PGJ(2). Furthermore, PGJ(2) induced a rapid and transient expression of apoptosis-related protooncogene, c-fos, in both cells. The gene transcriptional rate was remarkably inc reased approximately 3.3-fold in PGJ(2) treated cells, but the stabili ty of c-fos mRNA was not significantly changed. Inhibition of de novo protein synthesis with cycloheximide increased c-fos mRNA stability bu t not abrogated PGJ(2)-induced c-fos transcription. These data suggest that PGJ(2) 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.