Bisperoxovanadium compounds are potent PTEN inhibitors

FEBS Lett. 2004 May 21;566(1-3):35-8. doi: 10.1016/j.febslet.2004.03.102.

Abstract

The tumour suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) shares homology with protein tyrosine phosphatases (PTPases). Similarly, bisperoxovanadium (bpV) molecules that are well-established PTPase inhibitors were shown to inhibit PTEN, but at up to 100-fold lower concentrations. The preference and potency of the bpVs towards PTEN was validated in vivo as demonstrated by: (i) an increase of Ser473 phosphorylation of protein kinase B (PKB) at similar low nanomolar doses, (ii) the lack of any effect on the PKB phosphorylation in the PTEN negative cell line UM-UC-3, (iii) the ability to rescue Ly294002-induced phosphoinositide 3-kinase inhibition and (iv) a lack of tyrosine phosphorylation at low nanomolar doses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chromones / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Insulin / pharmacology
  • Mice
  • Morpholines / pharmacology
  • NIH 3T3 Cells
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / antagonists & inhibitors*
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphorylation
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / genetics
  • Tumor Suppressor Proteins / antagonists & inhibitors*
  • Tumor Suppressor Proteins / genetics
  • Tyrosine / metabolism
  • Vanadium Compounds / antagonists & inhibitors
  • Vanadium Compounds / chemistry
  • Vanadium Compounds / pharmacology*

Substances

  • Antineoplastic Agents
  • Chromones
  • Enzyme Inhibitors
  • Insulin
  • Morpholines
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Tumor Suppressor Proteins
  • Vanadium Compounds
  • bisperoxovanadium
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Tyrosine
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Phosphoric Monoester Hydrolases
  • Protein Tyrosine Phosphatases
  • phosphatidylinositol-3-phosphatase
  • PTEN Phosphohydrolase
  • PTEN protein, human