PKC ACTIVITY IN RAT C-6 GLIOMA-CELLS - CHANGES ASSOCIATED WITH CELL-CYCLE AND SIMVASTATIN TREATMENT

The parallel effects of simvastatin on cell cycle and PKC activity in rat C-6 glioma cells were investigated. Simvastatin, 2.5 mu M, for 24 h resulted in cell growth arrest in early G(1) phase of the cell cycle and in a significant increase of total PKC activity (283 +/- 42 vs 47 0 +/- 61 pmoles/min/mg protein p=0.002 for control cells and simvastat in-treated cells, respectively). The effect of simvastatin was fully p revented by mevalonate. A time dependent increase of PKC activity was observed in control exponentially free-growing C-6 cells approaching c onfluency: a highly significant negative correlation (r=-0.91 p<0.0001 ) between PKC activity and growth rate was calculated. PKC activity wa s high in cells arrested in G(0) by serum starvation (0.4%). Following addition of complete medium (17.5% serum) the PKC activity progressiv ely decreased and reached a minimum when cells traversed the G(2)/M ph ase, as determined by DNA analysis distribution. PKC activity dropped 30% in simvastatin-arrested early G(1) cells; 44% in hydroxyurea-arres ted cells at the G(1)/S boundary and 73% in Colcemid mitosis-blocked c ells. The results show that C-6 glioma cell PKC activity Is maximal in a G(0) quiescent state and varies at different points of the cell cyc le. (C) 1994 Academic Press, Inc.