The role of c-Myc and heat shock protein 70 in human hepatocarcinoma Hep3B cells during apoptosis induced by prostaglandin A2/Delta12-prostaglandin J2.

Prostaglandin (PG) A2 (PGA2) and Delta12-PGJ2 have potent antiproliferative activity on various tumor cell growths in vitro. In this study, we investigated the mechanism of PGA2/Delta12-PGJ2-mediated apoptosis, including intracellular apoptosis-related genes in human hepatocarcinoma Hep3B cells. Hep3B cells treated with PGA2/Delta12-PGJ2 showed that a time-dependent DNA fragmentation characterized by marked apoptosis and the elevation of c-myc mRNA expression. In proportion to the increased c-myc gene transcription, heat shock protein 70 (hsp70) mRNA was induced from 1 to 24 h after PGA2/Delta12-PGJ2 treatment. The transfection of c-myc antisense oligomers in Hep3B cells significantly delayed the induction of HSP70 expression and blocked formation of DNA fragmentation by PGA2/Delta12-PGJ2. Moreover, overexpressed HSP70 showed an increased resistance to apoptosis by PGA2/Delta12-PGJ2 treatment. These results demonstrated that the decreased survival in response to PGA2/Delta12-PGJ2 was causally related to the amount of c-myc and the induction of c-myc regulated the elevation of HSP70 which have been known to correlate with a resistance to apoptosis.