Human hepatocarcinoma cells (SK-HEP-1) were induced to die through apoptosis by treatment with Δ 1 2 -prostaglandin (PG)J 2 , as characterized by the appearance of a typical DNA ladder. The induction of apoptosis by Δ 1 2 -PGJ 2 was specifically blocked by cycloheximide (CHX). Western analysis using anti-p53 or anti-WAF1 monoclonal antibodies demonstrated that these two protein levels were increased 3 h after Δ 1 2 -PGJ 2 treatment, and accumulated for up to 12 h. The induction of p53 protein seemed to be dependent on the increase of p53 mRNA level, which was inhibited by CHX treatment. However, delayed addition of CHX after Δ 1 2 -PGJ 2 treatment failed to affect both p53 mRNA levels and DNA fragmentation following Δ 1 2 -PGJ 2 treatment, indicating that the inhibition of p53 synthesis may contribute to the protective effect of CHX against Δ 1 2 -PGJ 2 -mediated cytotoxicity. Therefore, our results suggest that the initial events caused by Δ 1 2 -PGJ 2 , leading ultimately to SK-HEP-1 cell death, involve a certain process required for p53 induction. However, the finding that Δ 1 2 -PGJ 2 is also active against Hep 3B cells which are devoid of a functional p53 indicates that p53 may not be the critical requirement for inducing apoptosis by Δ 1 2 -PGJ 2 .