Sodium vanadate inhibits apoptosis in malignant glioma cells: A role for Akt PKB

The dual signal hypothesis of apoptosis holds that a common signal can acti vate both apoptotic and proliferative pathways. The fate of a cell is depen dent on which of these two pathways predominates. In the MAPK family of kin ases, ERK and JNK have been proposed to mediate apoptosis whereas the PI3K- stimulated kinase, Akt/PKB, has been shown to inhibit apoptosis. The object of th is study was to determine the role of these kinases in a glioma mode l of apoptosis. We have previously shown that K252a induces apoptosis and i nhibits kinase activity. In this study we confirm these results and show th at the protein tyrosine phosphatase inhibitor sodium vanadate activates ERK , JNK and Akt/PKB, but does not stimulate proliferation. Vanadate did prote ct T98G cells from K252a-induced apoptosis, an effect that was abolished by addition of the PI3K inhibitor wortmannin. This suggests that PI3K and Akt /PKB may be responsible for mediating vanadate's protective effect on gliom a cells. We conclude that the intracellular balance between protein phospho rylation pathways is a critical determinant of both cell proliferation and cell death.