Prostaglandin A2 induces caspase-independent apoptosis in hepatocellular carcinoma cells.
OBJECTIVE
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.
Kim
Ho-Shik
HS
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Shim
Jae-Chun
JC
Choi
Ju-Youn
JY
Rhim
Hyangshuk
H
Kim
In-Kyung
IK
D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D011454:Prostaglandins A / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D061945:Caspase Inhibitors; D011454:Prostaglandins A; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C100008:prostaglandin A2