Mechanism of antiproliferative activity of luteolin against stilbene-estrogen stimulation of proliferation of hamster renal epithelial cells

In the present study, we have investigated the influence of a naturally occurring plant flavone luteolin on cell proliferation, nuclear tyrosine kinase activity, and expression of insulin-like growth factor-I (IGF-I) receptor in Syrian hamster renal epithelial cells. Diethylstilbestrol (DES)-induced cell proliferation was inhibited in a dose-dependent manner by cotreatment with luteolin. We also tested the influence of luteolin on nuclear protein tyrosine kinase activity and the expression of IGF-I receptor. The nuclear tyrosine kinase activity was inhibited in a dose-dependent manner by both genistein and luteolin. Luteolin was five times more effective in inhibiting nuclear tyrosine kinase activity than genistein. Data of kinetic constants suggest that luteolin is a noncompetitive inhibitor of nuclear protein tyrosine kinases. Co-treatment of luteolin significantly inhibited DES-induce IGF-I receptor expression. These findings indicate that blocking effects of DES-induced cell proliferation by luteolin may be through the inhibition of nuclear tyrosine kinase activity and of IGF-I receptor expression.