Inhibition of cell cycle progression by penta-acetyl geniposide in rat C6 glioma cells

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 G(0)/gap phase 1 (G(1)) 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 G(0)/G(1) phase was associated with a marked decrease in the protein expression of cyclin D-1, 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 D-1/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 G(0)/G(1) phase, was exerted by inducing the expression of p21 that, in turn, repressed the activity of cyclin D-1/cdk 4 and the phosphorylation of Rb. (C) 2004 Elsevier Inc. All rights reserved.