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.
Ahn
S G
SG
Department of Biochemistry, College of Medicine, The Catholic University of Korea, 505, Banpo-Dong, Socho-Ku, Seoul 137-701, South Korea.
Jeong
S Y
SY
Rhim
H
H
Kim
I K
IK
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011454:Prostaglandins A / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic
D000970:Antineoplastic Agents; D018840:HSP70 Heat-Shock Proteins; D009838:Oligodeoxyribonucleotides; D011453:Prostaglandins; D011454:Prostaglandins A; D016271:Proto-Oncogene Proteins c-myc; C040810:9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydroprostaglandin D2; C100008:prostaglandin A2; D015230:Prostaglandin D2