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

详细信息    查看全文

• 作者：Shigeyoshi Honma ; Masaki Saito ; Haruhisa Kikuchi ; Yoshinori Saito ; Yoshiteru Oshima ; Norimichi Nakahata ; Makoto Yoshida
• 关键词：Brefelamide ; Astrocytoma ; Growth inhibition ; Extracellular signal-regulated kinase ; Epidermal growth factor receptor
• 刊名：European Journal of Pharmacology
• 出版年：2009
• 出版时间：15 August 2009
• 年：2009
• 卷：616
• 期：1-3
• 页码：38-42
• 全文大小：455 K

文摘

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.