title: Bisperoxovanadium compounds are potent PTEN inhibitors.
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.
authors.affiliation: Department of Biological Sciences, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Annette C
authors.initials: AC
authors.lastname: Schmid
authors.forename: Richard D
authors.initials: RD
authors.lastname: Byrne
authors.forename: Ramón
authors.initials: R
authors.lastname: Vilar
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Woscholski
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D041681:NIH 3T3 Cells; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors* / Q000235:genetics; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism; D017968:Vanadium Compounds / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D002867:Chromones; D004791:Enzyme Inhibitors; D007328:Insulin; D009025:Morpholines; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D017968:Vanadium Compounds; C472777:bisperoxovanadium; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D014443:Tyrosine; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; C061816:phosphatidylinositol-3-phosphatase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human