Abstract
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 microM 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis*
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Blotting, Western
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Cell Line
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Cell Survival
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Chromones / pharmacology*
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Culture Media, Serum-Free / pharmacology
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Drug Resistance, Neoplasm*
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Enzyme Inhibitors / pharmacology*
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Humans
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Morpholines / pharmacology*
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Neoplasms / pathology
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Phenotype
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Phosphoinositide-3 Kinase Inhibitors*
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Poly(ADP-ribose) Polymerases / metabolism
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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RNA, Messenger / metabolism
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Signal Transduction
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Time Factors
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Tumor Cells, Cultured
Substances
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Chromones
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Culture Media, Serum-Free
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Enzyme Inhibitors
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Morpholines
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Phosphoinositide-3 Kinase Inhibitors
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Proto-Oncogene Proteins
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RNA, Messenger
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Poly(ADP-ribose) Polymerases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt