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 control of cellular metabolism. Sodium orthovanadate, a potent inhibitor of tyrosine phosphatases, in dose-dependent manner affected growth of C6 glioma cells and produced decrease in cell number and alterations in cellular morphology at 24 h after treatment. At high concentrations (>50 μM) orthovanadate reduced cell number, density of fine processes and cell contact followed by the appearance of spindle-shaped or round cells. After 48 h cells had no processes, the majority of cells were rounded and the number of cells gradually declined due to cell death. Furthermore 250 μM orthovanadate produced alterations in nuclear morphology as revealed by staining with fluorescent dye Hoechst 33258. Appearance of “bean” shaped nuclei, condensation of chromatin suggest that orthovanadate treatment results in cell death which bears all features of apoptosis. © 1997 John Wiley & Sons, Ltd.