The effects of calmodulin inhibitors (W-7, TFP) in cultured glioma cells

The effects of calmodulin inhibitors [W-7: N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide-HCl, TFP: Trifluoperazine]; cell growth inhibition, morphologic changes, and alterations of flow cytometry DNA hisotgram were studied in cultured glioma cells. The cell lines used in this experiment were KC and KY, which had been established from human glioblastomas, and C-6 from a methylnitrosourea-induced rat glioma. A dose-dependent growth inhibition was found in cells exposed to calmodulin inhibitors (W-7, TFP). The morphologic changes of cells were manifested by a rounding of the cells with numerous fine electron dense granules in the cytoplasm as early as 3 hours following exposure to calmodulin inhibitors. The influence of calmodulin inhibitors on cell kinetics was analysed by flow cytometry which revealed an accumulation of cells in G(2)+M phases within 24 hours after treatment. These results, together with the previous reports, indicate that the effects of calmodulin inhibitors on cell growth may be due not only to the inhibition of DNA synthesis in the G(1)/S boundary phase but also to the inhibition of tubulin disassembly in G(2)+M phases.