title: PKC activity in rat C6 glioma cells: changes associated with cell cycle and simvastatin treatment.
abstract: The parallel effects of simvastatin on cell cycle and PKC activity in rat C6 glioma cells were investigated. Simvastatin, 2.5 microM, 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.
authors.affiliation: Institute of Pharmacological Sciences, University of Milan, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Soma
authors.forename: R
authors.initials: R
authors.lastname: Baetta
authors.forename: S
authors.initials: S
authors.lastname: Bergamaschi
authors.forename: M R
authors.initials: MR
authors.lastname: De Renzis
authors.forename: C
authors.initials: C
authors.lastname: Davegna
authors.forename: F
authors.initials: F
authors.lastname: Battaini
authors.forename: R
authors.initials: R
authors.lastname: Fumagalli
authors.forename: S
authors.initials: S
authors.lastname: Govoni
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000201:enzymology / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D003703:Demecolcine / Q000494:pharmacology; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006918:Hydroxyurea / Q000494:pharmacology; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008798:Mevalonic Acid / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D019821:Simvastatin; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D019821:Simvastatin; D011493:Protein Kinase C; D008798:Mevalonic Acid; D006918:Hydroxyurea; D003703:Demecolcine