title: Preclinical evaluation of dipotassium bisperoxo (picolinato) oxovanadate V for the treatment of pediatric low-grade gliomas.
abstract: OBJECTIVE
  The treatment of pediatric low-grade gliomas with current treatment modalities still remains ineffective among a subset of patients; hence, justifying the need to further investigate more effective therapies. Dipotassium bisperoxo (picolinato) oxovanadate V (Bpv[pic]), is a derivative of the trace metal vanadium and a potent inhibitor of protein tyrosine phosphatases, which are important mediators of oncogenic and tumor suppressive activities in cancers. In this study, we undertook a preclinical evaluation of the antineoplastic functions of Bpv(pic) in the treatment of pediatric low-grade gliomas.
  
  
  METHODS
  We utilized pediatric low-grade glioma cell lines (Res186, Res259 and R286) in a wide variety of cancer assays to determine whether Bpv(pic) can abrogate the neoplastic properties of these cells.
  
  
  RESULTS
  Our preclinical evaluation of the antineoplastic properties of Bpv(pic) in pediatric low-grade gliomas reveals a significant dose-dependent decrease in cell viability as a consequence of decreased proliferation and sustained induction of growth arrest and apoptosis. Bpv(pic) significantly decreases cell migration/invasion and anchorage-independent growth in soft agarose. Within cells, Bpv(pic) functions by attenuating CDC25A activity, and by decreasing the expression of multiple protein tyrosine phosphatases, DNA repair genes, microtubule-associated genes, such as PLK1, AURKA and HDAC6, and conversely augmenting the expression of proapoptotic mediators such as BAK, AIFM and CTSL1.
  
  
  CONCLUSIONS
  Collectively, our data strongly suggest novel evidence of Bpv(pic) being a potent antineoplastic drug and a suitable alternative for the treatment of pediatric low-grade gliomas.
authors.affiliation: Department of Pediatrics, Laval University, 2705 Boulevard Laurier, Local RC9800, Québec, QC, G1V 4G2, Canada.
authors.forename: Norbert Fonya
authors.initials: NF
authors.lastname: Ajeawung
authors.forename: Robert
authors.initials: R
authors.lastname: Faure
authors.forename: Chris
authors.initials: C
authors.lastname: Jones
authors.forename: Deepak
authors.initials: D
authors.lastname: Kamnasaran
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000145:classification / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D009367:Neoplasm Staging; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010372:Pediatrics / Q000379:methods; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C428105:picolinato-oxodiperoxovanadate; C517004:CDC25A protein, human; D017027:Protein Tyrosine Phosphatases; D020687:cdc25 Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human