Inhibition of epidermal growth factor-induced DNA synthesis by tyrosine kinase inhibitors

FEBS Lett. 1990 Jan 29;260(2):198-200. doi: 10.1016/0014-5793(90)80102-o.

Abstract

We prepared methyl 2,5-dihydroxycinnamate as a stable analogue of erbstatin, a tyrosine kinase inhibitor. This analogue was about 4 times more stable than erbstatin in calf serum. It inhibited epidermal growth factor receptor-associated tyrosine kinase in vitro with an IC50 of 0.15 micrograms/ml. It also inhibited in situ autophosphorylation of epidermal growth factor receptor in A431 cells. Methyl 2,5-dihydroxycinnamate was shown to delay the S-phase induction by epidermal growth factor in quiescent normal rat kidney cells, without affecting the total amount of DNA synthesis. The effect of erbstatin on S-phase induction was smaller, possibly because of its shorter life time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cells, Cultured
  • DNA / biosynthesis*
  • Epidermal Growth Factor / antagonists & inhibitors
  • Epidermal Growth Factor / pharmacology*
  • ErbB Receptors / drug effects
  • ErbB Receptors / metabolism
  • Hydroquinones / pharmacology*
  • Kidney / drug effects
  • Kidney / metabolism*
  • Phosphorylation
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Rats
  • Thymidine / metabolism

Substances

  • Hydroquinones
  • Epidermal Growth Factor
  • DNA
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Thymidine
  • erbstatin