Korean J Hepatol.  2005 Mar;11(1):72-79.

Prostaglandin A2 Induces Caspase-independent Apoptosis in Hepatocellular Carcinoma Cells

• Kim HS
• Shim JC
• Choi JY
• Rhim H
• Kim IK

Abstract

BACKGROUND/AIMS: Prostaglandin (PG) A2 has been reported to inhibit the growth of hepatocellular carcinoma cells via activation of apoptosis, although the molecular mechanisms involved have not been clarified, yet. To investigate the mechanism of the PGA2-induced apoptosis, we analyzed the activation of caspases during the apoptosis of hepatoma cell lines. METHODS: Induction of apoptosis by PGA2 in hepatoma cell lines, Hep 3B and Hep G2, was assessed by DAPI staining of nuclei and agarose gel electrophoresis of genomic DNA. The involvement of caspases was analyzed by immunoblot analysis of poly ADP-ribose polymerase (PARP) and by checking the effect of caspase inhibitors on PGA2-induced apoptosis. RESULTS: PGA2 inhibited the growth of Hep 3B and Hep G2 cells, accompanying nuclear condensation and fragmentation, and genomic DNA laddering, which are the hallmarks of apoptosis. The PARP was not cleaved during the apoptosis of Hep 3B and Hep G2 cells and caspase inhibitors such as z-VAD-Fmk and z-DEVD-Fmk exerted no effect on the PGA2-induced apoptosis. CONCLUSIONS: These results suggest that PGA2 induces apoptosis in Hep 3B and Hep G2 cells via caspase-independent pathway.

Keyword

Prostaglandin A2; Hepatocellular carcinoma; Apoptosis; Caspase

MeSH Terms

Apoptosis/*drug effects
Carcinoma, Hepatocellular/*pathology
Caspases/antagonists & inhibitors/*metabolism
Cell Line, Tumor
Cell Proliferation/drug effects
Enzyme Activation
Humans
Liver Neoplasms/*pathology
Prostaglandins A/*pharmacology
Research Support, Non-U.S. Gov't
Tumor Cells, Cultured