Heat-processed neoginseng, KG-135, down-regulates G1 Cyclin-dependent kinase through the proteasome-mediated pathway in HeLa cells.
High temperature heat treatment of ginseng (Panax ginseng, C.A. Meyer) generates KG-135 (heat-processed neoginseng) which contains a mixture of three major ginseng saponins, ginsenosides Rk1, Rg3 and Rg5. Ginsenosides, particularly of the diol-type including Rk1, Rg3 and Rg5, have been shown to induce cell growth arrest in various cell types of human cancer. Herein, we report that KG-135 is able to arrest the cell cycle in human cervix adenocarcinoma HeLa cells. KG-135 arrests cells at the G1 phase of the cell cycle with an IC50 value of 69 microg/ml. The G1 phase arrest is associated with down-regulation of Cyclin D1/Cdk4 and Cyclin B1/Cdc2 activities in cells after treatment with KG-135. Furthermore, down-regulation of G1 Cyclin-dependent kinase activities is kinetically well related to the decreased intracellular protein levels of these kinases. In addition, the decrease in the levels of Cyclin D1/Cdk4 and Cyclin B1, but not of Cdc2, is similarly prevented by co-treatment of cells with MG-132, a potent proteasome inhibitor. Thus, the KG-135-induced arrest of the cell cycle at G1 phase in HeLa cells represents a novel mechanism that involves proteasome-mediated degradation of the Cyclins (Cyclin D1 and B1) and Cdk4 proteins.
Lee
Won-Hee
WH
Division of Pharmaceutical Biosciences, Seoul National University, Seoul 151-742, Korea.
Choi
Joon-Seok
JS
Kim
Hyun Young
HY
Park
Jeong-Hill
JH
Lee
Seung-Ki
SK
Surh
Young-Joon
YJ
D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D018844:Cyclin-Dependent Kinases / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D036145:Ginsenosides / Q000494:pharmacology*; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D047468:Immunoprecipitation; D005894:Panax / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
D036145:Ginsenosides; D018844:Cyclin-Dependent Kinases; D046988:Proteasome Endopeptidase Complex