The role of c-Myc and heat shock protein 70 in human hepatocarcinoma Hep3B cells during apoptosis induced by prostaglandin A2/Δ12-prostaglandin J2

Prostaglandin (PG) A(2) (PGA(2)) and Delta(12)-PGJ(2) have potent antiproliferative activity on various tumor cell growths in vitro. In this study, we investigated the mechanism of PGA(2)/Delta(12)-PGJ(2)-mediated apoptosis, including intracellular apoptosis-related genes in human hepatocarcinoma Hep3B cells. Hep3B cells treated with PGA(2)/Delta(12)-PGJ(2) 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 PGA(2)/Delta(12)-PGJ(2) 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 PGA(2)/Delta(12)-PGJ(2). Moreover, overexpressed HSP70 showed an increased resistance to apoptosis by PGA(2)/Delta(12)-PGJ(2) treatment. These results demonstrated that the decreased survival in response to PGA(2)/Delta(12)-PGJ(2) 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. (C) 1998 Elsevier Science B.V. All rights reserved.