Ginsenoside-Rg1 positively regulates cyclin E-dependent kinase activity in human hepatoma SK-HEP-1 cells.
In the present study, we describe that ginsenoside-Rg1 (G-Rg1) stimulates the proliferation of cultured human hepatoma SK-HEP-1 cells. The incorporation of [3H] thymidine into DNA was increased in the cells in response to G-Rg1. The stimulatory effect of G-Rg1 on DNA synthesis in SK-HEP-1 cells require newly synthesized proteins, since cycloheximide blocked the DNA synthetic activity stimulated with G-Rg1. Thus, we examined whether G-Rg1 induces the intracellular protein levels of regulatory proteins for cell cycle progression using immunoblottings. The results from immunoblottings showed that G-Rg1 induced the levels of cyclin E and cdk2 proteins in the cells. Furthermore, the results from immuno-complex kinase assays for cyclin E-dependent kinase showed that G-Rg1 up-regulates the kinase activity in a dose-dependent manner. These results suggest that G-Rg1 stimulates cell-growth of SK-HEP-1 cells by inducing the intracellular levels of cyclin E/cdk2 complex, which in turn up-regulates cyclin E-dependent kinase activity.
Lee
K Y
KY
College of Pharmacy, Seoul National University, Korea.
Lee
S K
SK
D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects*; D019927:Cyclin E; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D036145:Ginsenosides; D006657:Histones / Q000378:metabolism; D006801:Humans; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology
D019927:Cyclin E; D016213:Cyclins; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D006657:Histones; D012503:Saponins; D003513:Cycloheximide; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; C035054:ginsenoside Rg1