BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells

Amanda Thomaz, Mariane Jaeger, Marienela Buendia, Victorio Bambini-Junior, Lauro José Gregianin, Algemir Lunardi Brunetto, André T Brunetto, Caroline Brunetto de Farias, Rafael Roesler

Research output: Contribution to journalArticle (journal)peer-review

15 Citations (Scopus)

Abstract

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.
Original languageEnglish
Pages (from-to)326-333
Number of pages8
JournalJournal of Molecular Neuroscience
Volume59
Issue number3
DOIs
Publication statusPublished - 27 Nov 2015

Keywords

  • Antineoplastic Agents/pharmacology
  • Azepines/pharmacology
  • Benzamides/pharmacology
  • Brain Neoplasms/metabolism
  • Brain-Derived Neurotrophic Factor/pharmacology
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • Cell Survival/drug effects
  • Humans
  • Medulloblastoma/metabolism
  • Membrane Glycoproteins/antagonists & inhibitors
  • Protein Kinase Inhibitors/pharmacology
  • Protein-Tyrosine Kinases/antagonists & inhibitors
  • Receptor, trkB
  • Signal Transduction

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