Inhibition of epidermal growth factor receptor functions by tyrosine kinase inhibitors in NIH3T3 cells.
Epidermal growth factor (EGF) induces transformed phenotypes in EGF receptor-overexpressing NIH3T3 (ER12) cells. Tyrosine kinase inhibitors such as erbstatin and its stable analogue methyl 2,5-dihydroxycinnamate inhibited the EGF-induced phenotypic changes in these cells; while 5'-O-methylerbstatin, an inactive analogue, did not. Methyl 2,5-dihydroxycinnamate inhibited intracellular tyrosine kinase activity in EGF-treated ER12 cells. Methyl 2,5-dihydroxycinnamate also delayed the EGF-induced DNA synthesis from the quiescent phase ER12 cells without showing irreversible cytotoxicity. It inhibited the DNA synthesis most efficiently at the early G1 phase. Thus, tyrosine kinase inhibitors may modify malignant phenotypes in EGF receptor-overexpressing neoplasms.
Umezawa
K
K
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Sugata
D
D
Yamashita
K
K
Johtoh
N
N
Shibuya
M
M
D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis; D006873:Hydroquinones / Q000494:pharmacology*; D015151:Immunoblotting; D007700:Kinetics; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
D002934:Cinnamates; D005353:Fibronectins; D006873:Hydroquinones; C067472:methyl 2,5-dihydroxycinnamate; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C048212:erbstatin