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

Abstract

BACKGROUND/AIM:

Activation of AKT serine/ threonine kinase (AKT) predicts poor outcome in neuroblastoma, which highlights the potential of the AKT pathway as a promising target for neuroblastoma treatment. Several studies reported that blockade of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) reduces proliferation in glioblastoma or lung cancer by inhibiting AKT and extracellular signal-related kinase (ERK) pathways. In this study, we examined the effect of the AMPAR antagonist perampanel on human neuroblastoma cells.

MATERIALS AND METHODS:

Cell proliferation, caspase activity, and western blot assays were performed to determine the effect of perampanel on the KP-N-SI9s human neuroblastoma cell line.

RESULTS:

Perampanel inhibited cell proliferation without triggering apoptosis in neuroblastoma cells. Down-regulation of AKT protein levels, AKT phosphorylation, and ERK1/2 phosphorylation were also observed in neuroblastoma cells with perampanel treatment.

CONCLUSION:

Perampanel inhibits neuroblastoma cell proliferation through down-regulation of AKT and ERK pathways and has potential for the treatment of neuroblastoma.

• Authors: Akifumi Nozawa, Michio Ozeki, Mikako Matsuoka, Mina Nakama, Shiho Yasue, Saori Endo, Norio Kawamoto, Hidenori Ohnishi, Toshiyuki Fukao
• Journal: Anticancer research (Anticancer Res) Vol. 39 Issue 7 Pg. 3595-3599 (Jul 2019) ISSN: 1791-7530 [Electronic] Greece
• PMID: 31262884 (Publication Type: Journal Article)
• Copyright: Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antineoplastic Agents
• Nitriles
• Pyridones
• Receptors, AMPA
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• perampanel

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Down-Regulation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Neuroblastoma (drug therapy, metabolism)
• Nitriles
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Pyridones (pharmacology)
• Receptors, AMPA (antagonists & inhibitors)