Ginsenoside-Rh2 blocks the cell cycle of SK-HEP-1 cells at the G1/S boundary by selectively inducing the protein expression of p27kip1.
The mechanism of action by which ginsenoside-Rh2 (G-Rh2) suppresses the proliferation of SK-HEP-1 cells is reported. The results from flow cytometric analyses show that G-Rh2 arrested the cell cycle at the G1/S transition phase. The cyclin E-dependent kinase activity which had been immunoprecipitated with cyclin E-specific antibody was down-regulated in the cells in response to G-Rh2. The IC50 value required to down-regulate the kinase activity by 50% was approximately 0.75 microM. Immunoblotting analyses show that G-Rh2 selectively induced the expression of p27kip1 in a dose-dependent manner whereas it had no effect on the levels of cyclin E, cdk2, and p21WAF1. In addition, our data show that G-Rh2 reduced the protein levels of cdc25A at doses higher than 10 microM. Collectively, these data suggest that ginsenoside-Rh2 arrests the cell cycle at the G1/S transition phase by selectively inducing protein expression of p27Kip1 and, as a consequence, down-regulating cyclin E-dependent kinase activity.
Lee
K Y
KY
College of Pharmacy, Seoul National University, Kwanak-Gu, South Korea.
Park
J A
JA
Chung
E
E
Lee
Y H
YH
Kim
S I
SI
Lee
S K
SK
D000818:Animals; D019556:COS Cells / Q000187:drug effects / Q000378:metabolism; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D015536:Down-Regulation; D016193:G1 Phase / Q000187:drug effects; D036145:Ginsenosides; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D051381:Rats; D012503:Saponins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D025521:Tumor Suppressor Proteins
C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D036145:Ginsenosides; D008869:Microtubule-Associated Proteins; D012503:Saponins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C055305:ginsenoside Rh2; D018844:Cyclin-Dependent Kinases