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

Cancer Lett. 2003 Feb 10;190(1):31-6. doi: 10.1016/s0304-3835(02)00615-8.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Blotting, Western
  • Cell Line
  • Cell Survival
  • Chromones / pharmacology*
  • Culture Media, Serum-Free / pharmacology
  • Drug Resistance, Neoplasm*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Morpholines / pharmacology*
  • Neoplasms / pathology
  • Phenotype
  • Phosphoinositide-3 Kinase Inhibitors*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Chromones
  • Culture Media, Serum-Free
  • Enzyme Inhibitors
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Poly(ADP-ribose) Polymerases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt