Penta-acetyl
geniposide, (Ac)5-GP, the acetylated compound of
geniposide, is able to inhibit the growth of rat C6
glioma cells in culture and in the bearing rats. Our recent data indicated that the induction of cell apoptosis and cell cycle arrest at G0/gap phase 1 (G1) by (Ac)5-GP might be associated with the induction of p53 and c-Myc, and mediated via the apoptosis-related bcl-2 family
proteins. In this report, we further investigated the mechanism involved in the cell cycle arrest induced by (Ac)5-GP in C6
glioma cells. The inhibitory effect of (Ac)5-GP on the cell cycle progression of C6
glioma cells which arrested cells at the G0/G1 phase was associated with a marked decrease in the
protein expression of
cyclin D1, and an induction in the content of
cyclin-dependent kinase (cdk) inhibitor p21
protein. This effect was correlated with the elevation in p53 levels. Further immunoprecipitation studies found that, in response to the treatment, the formation of
cyclin D1/cdk 4 complex declined, preventing the phosphorylation of
retinoblastoma (Rb) and the subsequent dissociation of Rb/E2F complex. These results illustrated that the apoptotic effect of (Ac)5-GP, arresting cells at the G0/G1 phase, was exerted by inducing the expression of p21 that, in turn, repressed the activity of
cyclin D1/cdk 4 and the phosphorylation of Rb.