ORTHOVANADATE, AN INHIBITOR OF TYROSINE PHOSPHATASES, INDUCES APOPTOTIC CELL-DEATH OF RAT C6 GLIOMA-CELLS

Protein phosphorylation depends on the relative activities of protein kinases and phosphatases and is a major regulatory mechanism for the c ontrol of cellular metabolism. Sodium orthovanadate, a potent inhibito r of tyrosine phosphatases, in dose-dependent manner affected growth o f C6 glioma cells and produced decrease in cell number and alterations in cellular morphology at 24 h after treatment. At high concentration s (>50 mu M) orthovanadate reduced cell number, density of fine proces ses and cell contact followed by the appearance of spindle-shaped or r ound cells. After 48 h cells had no processes, the majority of cells w ere rounded and the number of cells gradually declined due to cell dea th. Furthermore 250 mu M orthovanadate produced alterations in nuclear morphology as revealed by staining with fluorescent dye Hoechst 33258 . Appearance of ''bean'' shaped nuclei, condensation of chromatin sugg est that orthovanadate treatment results in cell death which bears all features of apoptosis.