Caspase-3-dependent protein kinase C delta activity is required for the progression of Ginsenoside-Rh2-induced apoptosis in SK-HEP-1 cells.
Ginsenoside-Rh2 (G-Rh2) has been shown to induce apoptosis in a variety of cell types. In this study, we show that G-Rh2-induced apoptosis is accompanied by the mitochondrial release of cytochrome c and activation of caspase-3 in the human hepatoma cell line, SK-HEP-1. Furthermore, protein kinase C delta (PKCdelta) activity was markedly up-regulated in a lipid activator-independent manner with kinetics similar to those of PKCdelta and PARP cleavages during the apoptotic progression. Pre-treatment of cells with the caspase-3 specific inhibitor (z-DEVD-fmk) effectively prevented the G-Rh2-induced proteolytic activation of PKCdelta. Moreover, rottlerin, a specific PKCdelta inhibitor blocked G-Rh2-induced proapoptotic effects on the cells including the release of cytochrome c, activation of caspase-3 activity, and proteolytic cleavage and activation of PKCdelta. These results suggest that G-Rh2-induced apoptosis is functionally linked to mitochondrial dysfunction and caspase-3 activity is regulated by positive feedback with PKCdelta via the mitochondrial pathway.
Oh
Jeong-In
JI
Division of Pharmaceutical Biosciences, College of Pharmacy and The Research Institute for Pharmaceutical Sciences, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul, 151-742, South Korea.
Chun
Kwang-Hoon
KH
Joo
Sang-Hoon
SH
Oh
You-Take
YT
Lee
Seung-Ki
SK
D000098:Acetophenones / Q000494:pharmacology; D017209:Apoptosis; D001578:Benzopyrans / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000098:Acetophenones; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D036145:Ginsenosides; C055305:ginsenoside Rh2; D045304:Cytochromes c; C085746:rottlerin; D051745:Protein Kinase C-delta; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases