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Perampanel Inhibits Neuroblastoma Cell Proliferation Through Down-regulation of AKT and ERK Pathways

Akifumi Nozawa1, Michio Ozeki2, Mikako Matsuoka3

  • 1Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan.

Anticancer Research
|July 3, 2019
PubMed
Abstract

Insights

Perampanel, an alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor antagonist, inhibits neuroblastoma cell growth by reducing AKT and ERK pathway signaling. This suggests perampanel

Area of Science:

  • Oncology
  • Neuroscience
  • Pharmacology

Background:

  • Activation of AKT serine/threonine kinase (AKT) is linked to poor outcomes in neuroblastoma.
  • The AKT pathway is a potential therapeutic target for neuroblastoma treatment.
  • Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) inhibits AKT and ERK pathways in other cancers.

Purpose of the Study:

  • To investigate the effect of the AMPAR antagonist perampanel on human neuroblastoma cells.
  • To determine if perampanel affects neuroblastoma cell proliferation and associated signaling pathways.

Main Methods:

  • Human neuroblastoma cell line (KP-N-SI9s) was treated with perampanel.
  • Assays performed included cell proliferation, caspase activity, and Western blot analysis.
  • Western blot was used to assess protein levels and phosphorylation of AKT and ERK1/2.

Main Results:

  • Perampanel significantly inhibited neuroblastoma cell proliferation.
  • Apoptosis was not induced by perampanel treatment.
  • Perampanel treatment led to down-regulation of AKT protein levels, AKT phosphorylation, and ERK1/2 phosphorylation.

Conclusions:

  • Perampanel effectively inhibits neuroblastoma cell proliferation.
  • The mechanism involves the down-regulation of both AKT and ERK signaling pathways.
  • Perampanel demonstrates potential as a therapeutic agent for neuroblastoma treatment.
Keywords:
AMPA receptorAMPAR antagonistPediatric oncologyglutamate receptorsmolecular targeted therapy

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