LY294002, an inhibitor of phosphatidylinositol-3-kinase, causes preferential induction of apoptosis in human multidrug resistant cells

Protein kinase B (PKB), a kinase downstream of phosphatidylinositol 3-kinase (PI3-kinase) provides anti-apoptotic and survival signals via phosphorylation of various targets. Inhibiting PI3-kinase with a 12 h exposure to 10 muM LY294002 induces levels of apoptosis of 30.39 +/- 1.53% in the KB-V1 multidrug resistant (MDR) cell line compared to 4.54 +/- 1.00% in drug sensitive KB-3-1 cells (P < 0.001). This occurred in conjunction with a preferential reduction in activated PKB in MDR cells. These results suggest the PI3-kinase/PKB signalling pathway is important for the survival of MDR cells and inhibition of this pathway results in the selective induction of apoptosis in MDR cells. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.