A reduction of epidermal growth factor receptor is involved in brefelamide-induced inhibition of phosphorylation of ERK in human astrocytoma cells.
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 Tyr(1068), 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.
Honma
Shigeyoshi
S
Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare, Gunma 370-0033, Japan.
Saito
Masaki
M
Kikuchi
Haruhisa
H
Saito
Yoshinori
Y
Oshima
Yoshiteru
Y
Nakahata
Norimichi
N
Yoshida
Makoto
M
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001254:Astrocytoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism
D000577:Amides; D000970:Antineoplastic Agents; D010636:Phenols; C510885:brefelamide; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases