Prostaglandin A2 Induces Caspase-independent Apoptosis in Hepatocellular Carcinoma Cells.
- Author:
Ho Shik KIM
1
;
Jae Chun SHIM
;
Ju Youn CHOI
;
Hyangshuk RHIM
;
In Kyung KIM
Author Information
1. Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Korea. ikkim@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Prostaglandin A2;
Hepatocellular carcinoma;
Apoptosis;
Caspase
- MeSH:
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
- From:The Korean Journal of Hepatology
2005;11(1):72-79
- CountryRepublic of Korea
- Language:English
-
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.
