Carcinogenesis Advance Access originally published online on June 19, 2003
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Carcinogenesis, Vol. 24, No. 11, 1767-1772,
November 2003
© 2003 Oxford University Press
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Panaxadiol selectively inhibits cyclin A-associated Cdk2 activity by elevating p21WAF1/CIP1 protein levels in mammalian cells
1 Division of Pharmaceutical Biosciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea, 2 The Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea and 3 Department of Biochemistry, College of Medicine, Institute of Medical Research, Chungbuk National University, Cheongju 361-763, South Korea
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 µM 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.