title: Inhibition of epidermal growth factor receptor tyrosine kinase activity by hypericin.
abstract: The naphthodianthrone hypericin produces a potent and irreversible inhibition of the epidermal growth factor (EGF) receptor tyrosine kinase activity. The inhibition was time and temperature dependent but did not depend on EGF activation. The IC50 values obtained were 0.37-8.7 microM with membranes incubated for 30 min at 30 degrees or 10 min at 0 degree, respectively. Kinetic analyses with poly(Glu,Ala,Tyr) 6:3:1 [poly(GAT)] as an exogenous substrate were in agreement with the irreversible nature of the inhibition. Irradiation for 30 min with fluorescent light caused a dramatic photosensitizing effect and resulted in an IC50 value of 44 nM. This effect was due to a type I mechanism, since the exclusion of oxygen did not alter the inhibition curve. The inhibition was inversely proportional to the amounts of membranes used, which probably reflects the non-specific sequestration of hypericin into the lipid bilayer. Ser/Thr protein kinases such as protein kinase A, casein kinase 1 and 2 and the enzyme 5'-nucleotidase, were not inhibited by hypericin not even at high concentrations (> 100 microM).
authors.affiliation: Laboratorium voor Farmaceutische Biologie, Instituut voor Farmaceutische Wetenschappen, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: de Witte
authors.forename: P
authors.initials: P
authors.lastname: Agostinis
authors.forename: J
authors.initials: J
authors.lastname: Van Lint
authors.forename: W
authors.initials: W
authors.lastname: Merlevede
authors.forename: J R
authors.initials: JR
authors.lastname: Vandenheede
mesh_terms: D000818:Animals; D000873:Anthracenes; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008027:Light; D008566:Membranes / Q000187:drug effects; D051379:Mice; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000873:Anthracenes; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin; D066246:ErbB Receptors