A reduction of epidermal growth factor receptor is involved in brefelamide-induced inhibition of phosphorylation of ERK in human astrocytoma cells

Shigeyoshi Honma, Masaki Saito, Haruhisa Kikuchi, Yoshinori Saito, Yoshiteru Oshima, Norimichi Nakahata, Makoto Yoshida

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Brefelamide is an aromatic amide isolated from Dictyostelium cellular slime molds. We found that brefelamide has a potent inhibitory growth effect measured by MTT assay in 1321N1 human astrocytoma cells. The inhibition was associated with reduced phosphorylation of extracellular signal-regulated kinase (ERK). Brefelamide inhibited epidermal growth factor (EGF)-induced phosphorylation of ERK in a concentration-dependent manner. Furthermore, brefelamide diminished EGF-induced phosphorylation of EGF receptor at Tyr1068, a Grb2 binding site that leads to an activation of the Ras/Raf/ERK system. Brefelamide also reduced the expression level of the EGF receptor. These results suggest that one of the mechanisms of action of brefelamide is assumed to be inhibition of phosphorylation of ERK through a reduction of EGF receptor activity in 1321N1 human astrocytoma cells.

Original languageEnglish
Pages (from-to)38-42
Number of pages5
JournalEuropean journal of pharmacology
Volume616
Issue number1-3
DOIs
Publication statusPublished - 2009 Aug 15
Externally publishedYes

Keywords

  • Astrocytoma
  • Brefelamide
  • Epidermal growth factor receptor
  • Extracellular signal-regulated kinase
  • Growth inhibition

ASJC Scopus subject areas

  • Pharmacology

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