Bisperoxovanadium compounds are potent PTEN inhibitors

The tumour suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) shares homology with protein tyrosine phosphatases (PTPases). Similarly, bis-peroxovanadium (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. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.