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

Abstract	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.
Authors	S G Ahn, S Y Jeong, H Rhim, I K Kim
Journal	Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1448 Issue 1 Pg. 115-25 (Nov 19 1998) ISSN: 0006-3002 [Print] Netherlands
PMID	9824682 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents HSP70 Heat-Shock Proteins Oligodeoxyribonucleotides Prostaglandins Prostaglandins A Proto-Oncogene Proteins c-myc 9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydroprostaglandin D2 prostaglandin A2 Prostaglandin D2
Topics	Antineoplastic Agents (pharmacology) Apoptosis Carcinoma (metabolism) Cell Division (drug effects) Gene Expression Regulation HSP70 Heat-Shock Proteins (biosynthesis) Humans Liver Neoplasms (metabolism) Oligodeoxyribonucleotides (pharmacology) Prostaglandin D2 (analogs & derivatives, pharmacology) Prostaglandins (pharmacology) Prostaglandins A (pharmacology) Proto-Oncogene Proteins c-myc (biosynthesis, genetics) Transcription, Genetic

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