Ginsenoside-Rg5 suppresses cyclin E-dependent protein kinase activity via up-regulating p21Cip/WAF1 and down-regulating cyclin E in SK-HEP-1 cells.
In the present study, we report that ginsenoside-Rg5 (G-Rg5), a newly discovered diol-containing ginsenoside, blocks the cell cycle of human hepatoma SK-HEP-1 cells via the down-regulation of cyclin E-dependent kinase activity. The results from flow cytometric analyses show that G-Rg5 arrests the cell cycle of SK-HEP-1 cells at the Gl/S transition phase. The cyclin E-dependent kinase activity that has been immunoprecipitated with cyclin E-specific antibody is down-regulated in response to G-Rg5. The results from immunoblottings show that the down-regulation of cyclin E-dependent kinase activity is related to increased protein levels of p21Cip/WAF1 and to decreased protein levels of cyclin E, CDK2, and CDC25A. Collectively, these data suggest that G-Rg5 blocks cell cycle of SK-HEP-1 cells at the Gl/S transition phase by down-regulating cyclin E-dependent kinase activity and that the down-regulation of cyclin E-dependent kinase activity is caused mainly by induced CDK2 inhibitor, p21Cip/WAF1 and decreased levels of cyclin E.
Lee
K Y
KY
College of Pharmacy, Seoul National University, Korea.
Lee
Y H
YH
Kim
S I
SI
Park
J H
JH
Lee
S K
SK
D042846:CDC2-CDC28 Kinases; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000187:drug effects*; D016213:Cyclins / Q000502:physiology*; D036145:Ginsenosides; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects*; D012503:Saponins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D036145:Ginsenosides; D012503:Saponins; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases