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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Cell Survival / drug effects
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Chromones / pharmacology
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Humans
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Inhibitory Concentration 50
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Insulin / pharmacology
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Mice
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Morpholines / pharmacology
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NIH 3T3 Cells
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PTEN Phosphohydrolase
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Phosphoric Monoester Hydrolases / antagonists & inhibitors*
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Phosphoric Monoester Hydrolases / genetics
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Phosphorylation
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Protein Serine-Threonine Kinases*
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Protein Tyrosine Phosphatases / antagonists & inhibitors
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / genetics
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Tumor Suppressor Proteins / antagonists & inhibitors*
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Tumor Suppressor Proteins / genetics
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Tyrosine / metabolism
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Vanadium Compounds / antagonists & inhibitors
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Vanadium Compounds / chemistry
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Vanadium Compounds / pharmacology*
Substances
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Antineoplastic Agents
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Chromones
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Enzyme Inhibitors
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Insulin
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Morpholines
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Proto-Oncogene Proteins
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Recombinant Proteins
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Tumor Suppressor Proteins
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Vanadium Compounds
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bisperoxovanadium
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Tyrosine
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Phosphoric Monoester Hydrolases
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Protein Tyrosine Phosphatases
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phosphatidylinositol-3-phosphatase
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PTEN Phosphohydrolase
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PTEN protein, human