Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells.
Ginsenoside Rh2 (G-Rh2) isolated from the root of Panax ginseng has been shown to have anti-cancer proliferation, differentiation and chemopreventive effects in certain cancer cell types. We investigated the mechanism of G-Rh2-induced growth inhibition in MCF-7 human breast carcinoma cells. G-Rh2 significantly inhibited the cell growth in a concentration-dependent manner, which effect was reversible, and induced a G1 arrest in cell cycle progression. G-Rh2 treatment down-regulated the protein level of cyclin D3 but upregulated the expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1. The increased levels of p21 were associated with increased binding of p21 and Cdk2 concomitant with marked decrease in Cdk2 and cyclin E-dependent kinase activities with no changes in Cdk2 and cyclin E expression. G-Rh2 markedly reduced the phosphorylated retinoblastoma protein (pRb) and enchanced association of unphosphorylated pRb and the transcription factor E2F-1. These data suggest that G-Rh2 inhibited the growth of MCF-7 cells, by inducing protein expression of p21 and reducing the protein levels of cyclin D which resulted in the down-regulation of cyclin/Cdk complex kinase activity, decreasing phosphorylation of pRb, and inhibiting E2F release.
Oh
M
M
Department of Pharmacy, Pusan National University, Pusan 609-735, Korea.
Choi
Y H
YH
Choi
S
S
Chung
H
H
Kim
K
K
Kim
S I
SI
Kim
D K
DK
Kim
N D
ND
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D056741:Cyclin D; D019927:Cyclin E; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016193:G1 Phase / Q000187:drug effects*; D036145:Ginsenosides; D006801:Humans; D005894:Panax / Q000737:chemistry; D010766:Phosphorylation; D010946:Plants, Medicinal; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D012503:Saponins / Q000494:pharmacology*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056741:Cyclin D; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D036145:Ginsenosides; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D012503:Saponins; D050680:Transcription Factor DP1; D014157:Transcription Factors; C055305:ginsenoside Rh2; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases