Panaxadiol selectively inhibits cyclin A-associated Cdk2 activity by elevating p21WAF1/CIP1 protein levels in mammalian cells.
We show that panaxadiol (PD), a ginseng saponin with a dammarane skeleton, selectively interferes with the cell cycle in human cancer cell lines. PD inhibited DNA synthesis in a dose-dependent manner with IC50 values ranging from 0.8 to 1.2 micro M in SK-HEP-1 cells and HeLa cells. PD-treated cells were arrested at G1/S phase, which coincided well with decreases in Cyclin A-Cdk2 activity, but not in Cyclin E-Cdk2 and Cdc2 activities. The intracellular levels of p21WAF1/CIP1 were significantly and selectively elevated in a dose- and time-dependent manner in PD-treated HeLa cells. Similarly, levels of the p21WAF1/CIP1 protein that is associated with the Cyclin A-Cdk2 complex increased, and these increases correlated well with the down-regulation of Cyclin A-Cdk2 activity. Thus, PD selectively elevates p21WAF1/CIP1 levels and thereby arrests the cell cycle at G1/S phase by down-regulating Cyclin A-Cdk2 activity.
Jin
Ying Hua
YH
Division of Pharmaceutical Biosciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Choi
JoonSeok
J
Shin
Soona
S
Lee
Kwang Youl
KY
Park
Jeong Hill
JH
Lee
Seung Ki
SK
D042846:CDC2-CDC28 Kinases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016193:G1 Phase; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D016196:S Phase; D014315:Triterpenes / Q000494:pharmacology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D036145:Ginsenosides; D014315:Triterpenes; C004564:panaxadiol; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2