PKC activity in rat C6-glioma cells: Changes associated with cell cycle and simvastatin treatment

The parallel effects of simvastatin on cell cycle and PKC activity in rat C₆ glioma cells were investigated. Simvastatin, 2.5 μM, for 24 h resulted in cell growth arrest in early G₁ phase of the cell cycle and in a significant increase of total PKC activity (283 ± 42 vs 470 ± 61 pmoles/min/mg protein p = 0.002 for control cells and simvastatin-treated cells, respectively). The effect of simvastatin was fully prevented by mevalonate. A time dependent increase of PKC activity was observed in control exponentially free-growing C₆ cells approaching confluency: a highly significant negative correlation (r = -0.91, p <0.0001) between PKC activity and growth rate was calculated. PKC activity was high in cells arrested in G₀ by serum starvation (0.4%). Following addition of complete medium (17.5% serum) the PKC activity progressively decreased and reached a minimum when cells traversed the G₂/M phase, as determined by DNA analysis distribution. PKC activity dropped 30% in simvastatin-arrested early G₁ cells; 44% in hydroxyurea-arrested cells at the G₁/S boundary; and 73% in Colcemid mitosis-blocked cells. The results show that C₆ glioma cell PKC activity is maximal in a G₀ quiescent state and varies at different points of the cell cycle.