Induction of c-fos protooncogene transcription and apoptosis by Δ12-prostaglandin J2 in human Pl-21 myeloid leukemia and RC-K8 pre-B lymphoma cells

Abstract

Δ¹²-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 PGD₂. 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.